Scientific terms used across GloNeuro, explained in simple language.
The ratio of a nucleic acid sample’s light absorbance at 260 nanometres to that at 280 nanometres, used to judge its purity. Pure DNA gives about 1.8 and pure RNA about 2.0; lower values suggest contamination with protein or phenol.
See also RNA integrity number, RT-qPCR.
The neurotransmitter that motor neurons use to activate muscles. In the brain it takes part in attention, learning and memory.
See also Motor neuron.
A brief, all-or-none electrical impulse that travels along an axon. Sodium channels open and the inside of the membrane briefly becomes positive, then potassium channels restore it.
See also Ion channel, Resting membrane potential.
A measure of how well two ways of grouping the same items agree, corrected for agreement expected by chance. A value of one means identical groupings; values near zero mean chance-level agreement.
See also Single-cell RNA sequencing.
A slab of jelly-like agarose through which DNA fragments are pulled by an electric field. Smaller fragments move faster, so fragments separate by size and appear as bands when stained.
See also DNA ladder, PCR.
The condition of a person in the period before death, such as a prolonged illness with low oxygen or fever, compared with a sudden death. It can affect the quality of RNA and proteins in donated tissue.
See also Post-mortem interval, Brain bank, RNA integrity number.
A molecule, such as a neurotransmitter or drug, that binds a receptor and activates it.
See also Antagonist, Receptor.
One of the different versions of a gene. Most animals carry two alleles of each gene, one inherited from each parent.
See also Genotype, Heterozygous, Homozygous.
A protein found at synapses that can misfold and clump into Lewy bodies, the hallmark of Parkinson’s disease and dementia with Lewy bodies.
See also Substantia nigra.
The stretch of DNA copied in a PCR, defined by the positions of the two primers; also the product itself. Amplicon sequencing reads many copies of it to identify variants.
See also PCR, PCR primer, Melt curve.
The fraction of template molecules copied in each PCR cycle, where 100% means exact doubling. It is usually calculated from the slope of a standard curve as 10^(−1/slope) − 1, so that a slope of about −3.32 corresponds to 100%.
See also Standard curve, Quantification cycle, Delta-delta Cq method.
An almond-shaped group of nuclei deep in the temporal lobe that helps detect threats and attach emotional meaning to experiences.
See also Emotion, Limbic system.
A protein fragment that can clump into plaques between neurons, one of the defining features of Alzheimer’s disease.
See also Tau, Neurodegeneration.
A molecule that binds a receptor without activating it and so blocks the action of agonists. A competitive antagonist competes with the agonist for the same binding site.
See also Agonist, Schild analysis.
Treatment of fixed tissue sections, usually by heating them in a buffer, that partly reverses the masking of epitopes by formalin crosslinks so that antibodies can bind again.
See also Epitope, Tissue fixation, Immunohistochemistry.
A labelled nucleic acid with a sequence complementary to the target RNA, so that it binds that RNA in in situ hybridisation. A sense probe, identical to the target, should not bind and is used as a control.
See also In situ hybridisation.
A statistical relationship between two variables, in which the value of one gives information about the likely value of the other. An association does not by itself show that one variable causes the other.
See also Correlation, Causation, Confounder.
A star-shaped glial cell of the brain and spinal cord. Astrocytes regulate the chemical surroundings of neurons, take part in the blood–brain barrier and respond to injury.
See also Glial cell, Blood–brain barrier.
Selecting some information for further processing while ignoring the rest.
See also Cognition.
Temporary sensory symptoms, most often visual such as flickering zigzag lines, that come before or with some migraine attacks. A slow wave of activity spreading across the cortex is thought to cause it.
See also Migraine.
Fluorescence that comes from the tissue itself, for example from lipofuscin, red blood cells or aldehyde fixation, rather than from a deliberately added label.
See also Lipofuscin, Sudan Black B, Fluorophore.
The part of the nervous system that controls body functions without conscious effort, such as heart rate, blood pressure, digestion and sweating. It has sympathetic and parasympathetic divisions.
See also Hypothalamus.
The long, thin extension of a neuron that carries its electrical output, the action potential, away from the cell body to other cells.
See also Action potential, Myelin.
A group of deep nuclei, including the caudate, putamen and globus pallidus, that help select and smooth movements and take part in habits and reward.
See also Dopamine, Substantia nigra.
A colour-based test for the total amount of protein in a sample. Protein produces a purple colour with the bicinchoninic acid reagent, and its intensity is compared with standards of known concentration.
See also Western blot.
Brain-derived neurotrophic factor: a secreted protein of the neurotrophin family that acts mainly through the TrkB receptor to support the survival and growth of neurons and the strengthening of synapses.
See also Synaptic plasticity, ELISA.
A spurious association between two conditions that arises when a sample is selected on either of them, for example by studying only hospital patients. It is an example of collider bias.
See also Collider, Selection bias.
Biological replicates are independent samples, such as different animals or cultures, that capture natural variation; technical replicates are repeated measurements of the same sample that capture measurement error.
See also Pseudoreplication, Sample size.
The tightly sealed walls of the brain’s blood vessels, supported by astrocytes, that control which substances pass from the blood into the brain.
See also Astrocyte.
A test of how strongly the data support each branch of a phylogenetic tree. Columns of the alignment are resampled at random with replacement many times, a tree is built from each resample, and the percentage of these trees containing a branch is its bootstrap support.
See also Phylogenetic tree, Sequence alignment.
A colour-based test for total protein in which the dye Coomassie Brilliant Blue G-250 binds protein and turns from brown-red to blue, measured at about 595 nanometres against standards of known concentration.
See also BCA assay, Standard curve.
Nine aspects of an association, set out by Austin Bradford Hill in 1965, to weigh when judging whether it is likely to be causal: strength, consistency, specificity, temporality, biological gradient, plausibility, coherence, experiment and analogy. Only temporality, the cause coming before the effect, is essential.
See also Causation, Association.
A reference map of the brain that names regions and gives them coordinates, so that findings from different studies can be placed in the same space.
An organisation that collects, characterises, stores and distributes brains and other nervous tissue donated after death for research, together with information about the donors.
See also Post-mortem interval, Agonal state.
Rhythmic electrical activity produced when large groups of neurons fire together, named by frequency: delta, theta, alpha, beta and gamma. Also called a neural oscillation.
See also EEG.
The stalk at the base of the brain, made of the midbrain, pons and medulla. It controls breathing, heart rate and sleep and relays signals to and from the spinal cord.
See also Cerebellum.
A way of amplifying the signal, rather than the target, in nucleic acid detection: probes bound to the target RNA are built up by successive hybridisation steps into a branched scaffold that carries many labelled molecules. Variants of it underlie several sensitive RNA in situ methods.
See also In situ hybridisation, Antisense probe.
The protein product of an immediate early gene that neurons make within an hour or so of strong activity. Staining for it is used to map which cells were recently active.
See also Immediate early gene, Immunohistochemistry.
Measuring neuronal activity by imaging a fluorescent indicator, such as GCaMP, whose brightness rises when calcium enters the cell during firing.
See also ΔF/F, Two-photon microscopy.
An observational study that starts from people who have an outcome (cases) and people who do not (controls), and compares how often each group was exposed to a possible cause in the past.
See also Odds ratio, Recall bias, Cohort study.
The relationship in which a change in one variable produces a change in another. Showing causation requires ruling out chance, bias, confounding and reverse causation, which an association alone cannot do.
See also Association, Confounder, Counterfactual.
Complementary DNA: DNA copied from an RNA template by reverse transcriptase. It is stable and can be amplified by PCR, so it is used to measure or clone the RNA it came from.
See also RT-qPCR, Messenger RNA.
The part of a neuron that contains the nucleus and most of the machinery for making proteins. Also called the soma.
See also Neuron.
The brain and spinal cord. Often abbreviated CNS.
See also Peripheral nervous system, Spinal cord.
A large, densely folded structure at the back of the brain that coordinates movement, balance and timing and contributes to some kinds of learning.
See also Purkinje cell.
The folded outer layer of grey matter covering the cerebrum, a few millimetres thick. Most of it, the neocortex, has six layers of cells.
See also Gyrus and sulcus, Grey matter.
The clear fluid that fills the ventricles and surrounds the brain and spinal cord, cushioning them and carrying away waste. Often abbreviated CSF.
See also Ventricles, Meninges.
The largest part of the brain, made of the two cerebral hemispheres with their cortex, white matter and deep nuclei.
See also Cerebral cortex.
A statistical test that compares counts observed in categories with the counts expected under a hypothesis, such as offspring genotypes against a Mendelian ratio.
See also Mendelian ratio, P-value.
Chromatin immunoprecipitation followed by high-throughput sequencing of the recovered DNA, which maps the binding sites of a protein, or the positions of a histone mark, across the whole genome.
See also Chromatin immunoprecipitation, CUT&RUN.
The material of chromosomes: DNA packaged with proteins, chiefly histones. How tightly chromatin is packed at a gene affects whether the gene can be transcribed.
See also Histone, Nucleosome, Chromatin immunoprecipitation.
A method for finding where a protein binds DNA in cells. Proteins are crosslinked to DNA, the chromatin is fragmented, an antibody pulls down the protein of interest and the DNA that comes with it is measured by qPCR (ChIP-qPCR) or sequencing (ChIP-seq).
See also ChIP-seq, Immunoprecipitation, Percent input.
A roughly 24-hour cycle in the body’s physiology and behaviour, set by a master clock in the hypothalamus and reset daily by light.
See also Hypothalamus, Sleep.
A study in people that tests whether a treatment is safe and works, usually in phases from small safety studies to large comparisons.
See also Randomisation and blinding.
Immunoprecipitation of one protein to see whether another protein comes down with it, which suggests the two are part of the same complex in the sample. It does not show whether they bind directly.
See also Immunoprecipitation, Isotype control, Western blot.
A group of three consecutive nucleotides in DNA or mRNA that specifies one amino acid or a signal to stop translation. Of the 64 possible codons, 61 encode amino acids and 3 are stop codons.
See also Messenger RNA, Synonymous substitution.
An estimate of the precision of a stereological estimate for one individual, reflecting the variation introduced by sampling only part of the structure. It is usually kept well below the biological variation between individuals.
See also Stereology, Coefficient of variation.
The standard deviation of a set of measurements divided by their mean, usually given as a percentage. It expresses variability relative to the size of the measurement, for example between replicate wells of an assay.
See also Limit of quantification, Biological and technical replicates.
The mental processes of knowing: perceiving, attending, remembering, reasoning, using language and solving problems.
See also Executive function, Memory.
An observational study that follows a group of people over time, recording their exposures and the outcomes that later develop. It can be prospective, following people forwards, or retrospective, using records collected in the past.
See also Risk ratio, Case–control study, Cross-sectional study.
A variable that is caused by two other variables. Adjusting for a collider, or selecting a sample on it, can create a spurious association between its two causes.
See also Confounder, Berkson’s bias, Directed acyclic graph.
A graph of the response to a drug against its concentration, usually on a logarithmic axis, which typically gives an S-shaped curve. Its position, steepness and top describe the drug’s potency and efficacy.
See also EC50, Hill slope, Emax.
A mild traumatic brain injury caused by a blow or jolt to the head, which temporarily disturbs how the brain works.
See also Brainstem.
A range of values, calculated from the data, that is likely to contain the true value of a quantity. A 95% confidence interval is built by a method that captures the true value in 95% of repeated studies.
See also Effect size, P-value.
A variable that influences both the exposure and the outcome of a study, so that it can create, hide or distort an apparent effect of the exposure. A confounder is not itself on the causal path from exposure to outcome.
See also Collider, Mediator, Directed acyclic graph.
A complete map of the connections in a nervous system, at the level of individual synapses or of large pathways between regions.
See also Tractography, White matter.
The state of being aware of oneself and one’s surroundings. How the brain produces conscious experience remains one of the major open questions in science.
The extent to which a test or measurement actually captures the concept it is intended to measure, such as whether a maze task measures spatial memory rather than swimming ability.
See also Internal validity, External validity.
The largest bundle of white matter in the brain, connecting the left and right cerebral hemispheres.
See also White matter.
An association in which two numerical variables tend to rise and fall together (a positive correlation) or one tends to fall as the other rises (a negative correlation). Its strength is summarised by a correlation coefficient between −1 and +1.
See also Association, Pearson’s correlation coefficient, Spearman’s rank correlation.
What would have happened to the same individuals under a different exposure or treatment. A causal effect is defined as the difference between the actual and the counterfactual outcome, only one of which can ever be observed.
See also Causation, Randomised controlled trial.
A second, general stain, such as DAPI for nuclei, added to show the overall tissue or cell layout around the specific label.
See also DAPI, Nissl stain.
A rectangle placed over the image in stereology with inclusion and exclusion edges: a cell is counted if it lies inside the frame or touches an inclusion edge, and not if it touches an exclusion edge, so that no cell is counted twice.
See also Disector, Optical fractionator.
An enzyme from a bacteriophage that cuts and rejoins DNA at loxP sites. Mice that make Cre only in particular cells are crossed with floxed mice to delete or switch on genes in just those cells.
See also Floxed allele, Knockout.
cAMP response element-binding protein: a transcription factor that binds the cAMP response element (CRE) in the promoters of many genes, including Fos. It is activated by phosphorylation when calcium or cAMP signalling rises in neurons, and is important for long-term memory.
See also Transcription factor, Immediate early gene, c-Fos.
A gene-editing system in which the Cas9 enzyme is guided by a short RNA to a matching DNA sequence and cuts both strands there. The cell’s repair of the cut can disrupt or change the gene.
See also Guide RNA, Protospacer adjacent motif.
An observational study that measures exposures and outcomes at a single point in time. It shows how common a condition is, but usually cannot show which came first.
See also Cohort study, Case–control study.
Joining molecules together with covalent chemical bonds. In chromatin immunoprecipitation, formaldehyde crosslinks proteins to the DNA they are bound to, and fixation with formalin crosslinks proteins in tissue.
See also Chromatin immunoprecipitation, Sonication, Tissue fixation.
Computed tomography: an X-ray scanner that makes cross-sectional pictures. It is fast and is widely used to detect bleeding after a stroke or head injury.
See also Ischaemic and haemorrhagic stroke.
A recording mode in which a chosen current is injected into a cell while its membrane voltage is measured, so that action potentials and other voltage changes can be seen.
See also Patch clamp, Voltage clamp.
Cleavage Under Targets and Release Using Nuclease: an alternative to ChIP in which an antibody bound to a protein in intact nuclei guides a nuclease fused to protein A (or protein A/G) to cut the DNA around it, releasing only the bound fragments for sequencing. It needs fewer cells and gives lower background than ChIP-seq.
See also ChIP-seq, Chromatin immunoprecipitation.
A blue fluorescent dye that binds DNA and so marks the nucleus of every cell. It is the most common nuclear counterstain.
See also Counterstain, Fluorophore.
A signalling protein enriched in the medium spiny neurons of the striatum, the main neurons of the basal ganglia, where it is used as a marker for them.
See also Basal ganglia, Dopamine.
The number of days since cells were placed in culture, used to state the age of a culture.
See also Primary culture, In vivo, in vitro, ex vivo and in silico.
Treatment in which electrodes implanted deep in the brain deliver electrical pulses, used for some people with Parkinson’s disease, tremor, dystonia or epilepsy.
See also Basal ganglia.
A way of calculating relative gene expression from quantitative PCR. The Cq of the target is first corrected by that of the reference genes (ΔCq) and then compared with the control group (ΔΔCq), giving a fold change of 2^−ΔΔCq if both amplify at close to 100% efficiency.
See also Quantification cycle, Reference gene, Amplification efficiency.
A decline in memory, thinking or other mental abilities severe enough to affect daily life. It has many causes, of which Alzheimer’s disease is the most common.
See also Neurodegeneration.
Damage to or loss of the myelin around axons, which slows or blocks nerve signals, as in multiple sclerosis.
See also Myelin.
A branching extension of a neuron that receives signals from other neurons, mostly through synapses on its surface.
See also Dendritic spine, Synapse.
A small protrusion on a dendrite that receives a single excitatory synapse. Spines can grow, shrink or disappear as connections strengthen or weaken.
See also Synaptic plasticity.
Measuring the darkness or brightness of bands on a gel or blot image to estimate how much material each band contains.
See also Western blot, Loading control.
How precisely an experimental design allows the effects of interest to be estimated. In fMRI it depends on the order, spacing and timing of trials relative to the slow haemodynamic response.
See also General linear model, Haemodynamic response function.
A molecule with a water-loving and a fat-loving part that dissolves cell membranes and releases proteins. Ionic detergents such as SDS unfold proteins, whereas milder non-ionic detergents such as Triton X-100 tend to keep protein complexes intact.
See also Triton X-100, Lysate, SDS-PAGE.
A mirror that reflects some wavelengths and lets others pass. In a fluorescence microscope it typically reflects the shorter excitation light onto the sample and passes the longer emitted light to the eye or camera.
See also Filter cube.
A method that estimates an effect by comparing the change in an outcome over time in a group that received an exposure with the change over the same period in a group that did not. It assumes the two groups would otherwise have followed parallel trends.
See also Natural experiment, Regression discontinuity.
Separating the parts of a homogenate by spinning it repeatedly at increasing speeds, so that larger and denser particles, such as nuclei, form a pellet before smaller ones, such as membranes and synaptosomes.
See also Homogenate, Sucrose density gradient, Synaptosome.
An MRI method that measures how water moves in tissue. Because water moves most easily along axons, it can be used to trace white-matter pathways.
See also Tractography.
A causal diagram in which variables are drawn as points and assumed causal effects as arrows, with no path leading back to its starting point. It shows which variables are confounders, mediators or colliders and so which to adjust for.
See also Confounder, Collider, Mediator.
A stereological probe that counts particles, such as cells, within a known volume by counting only those that appear between two parallel planes, so that each is counted once regardless of its size or shape. In the optical disector the planes are focal planes within a thick section.
See also Optical fractionator, Counting frame, Guard zone.
A mixture of DNA fragments of known sizes run alongside samples on a gel, so that the sizes of sample bands can be estimated. Protein gels use similar molecular-weight markers.
See also Agarose gel, SDS-PAGE.
Deoxyribonuclease I, an enzyme that cuts DNA into small fragments. It is used to remove contaminating genomic DNA from RNA samples before reverse transcription.
See also No-RT control, RNase.
A neurotransmitter involved in movement, motivation, reward and learning. The loss of dopamine-making neurons in the substantia nigra causes the movement symptoms of Parkinson’s disease.
See also Substantia nigra, Basal ganglia.
In single-cell sequencing, a droplet or well that captured two cells instead of one, so its profile mixes two cells and can look like a false new cell type.
See also Single-cell RNA sequencing.
Treatment with DpnI, an enzyme that cuts only methylated DNA. After site-directed mutagenesis by PCR, it destroys the original bacterial plasmid while leaving the newly made, unmethylated copies intact.
See also PCR.
The concentration of a drug that produces half of its maximal effect, a measure of potency: the lower the EC50, the more potent the drug. pEC50 is its negative base-10 logarithm in molar units, so a higher pEC50 means a more potent drug.
See also Concentration–response curve, Hill slope.
The error of concluding that a relationship seen between groups, such as countries or regions, also holds for the individuals within them.
See also Correlation, Association.
Electroencephalography: recording the brain’s electrical activity through electrodes on the scalp. It is central to the diagnosis of epilepsy and the study of sleep.
See also Brain rhythm, Epilepsy.
A measure of how large a difference or relationship is, rather than only whether it is statistically significant. Standardised effect sizes such as Cohen’s d and Hedges’ g express a difference between groups in units of their spread.
See also Statistical power, Confidence interval.
Recording the electrical activity of muscles, usually with electrodes on the skin over the muscle. Often abbreviated EMG.
See also Motor evoked potential.
The measurement of electrical activity in cells and tissue, from single ion channels to whole-brain recordings.
See also Patch clamp, EEG.
Enzyme-linked immunosorbent assay: a plate-based test that measures a protein with antibodies and an enzyme that produces a colour or light signal. In a sandwich ELISA the protein is captured by one antibody and detected by a second that binds a different epitope.
See also Standard curve, Epitope, Hook effect.
The largest response a drug can produce, however high its concentration: a measure of efficacy rather than potency.
See also Concentration–response curve, Agonist.
A response to an event that involves feelings, changes in the body and tendencies to act, such as fear, joy or anger.
See also Amygdala.
In subcellular fractionation, how much more concentrated a protein is in a fraction than in the starting homogenate, calculated as the signal per microgram of protein in the fraction divided by that in the homogenate. Values above 1 mean enrichment and below 1 depletion.
See also Homogenate, Synaptosome, Postsynaptic density.
A glial cell that lines the fluid-filled ventricles of the brain and the central canal of the spinal cord, and helps move cerebrospinal fluid.
See also Ventricles, Cerebrospinal fluid.
A long-term condition in which a person has a lasting tendency to have repeated, unprovoked seizures.
The particular part of an antigen, usually a short stretch of amino acids or a small surface patch of a protein, that an antibody recognises and binds.
See also Primary and secondary antibody, Antigen retrieval, ELISA.
A characteristic voltage waveform in the EEG that is time-locked to an event such as a stimulus or response, revealed by averaging many trials. Often abbreviated ERP.
A synaptic signal that makes the receiving neuron more likely to fire an action potential.
See also Glutamate, Inhibition.
The excitation spectrum shows how strongly a fluorophore absorbs each wavelength of light; the emission spectrum shows which wavelengths it gives out. Filters are chosen to match both.
See also Fluorophore, Stokes shift, Filter cube.
A small, brief depolarisation of the receiving neuron caused by an excitatory synapse, usually through glutamate receptors. Several of them added together can trigger an action potential. Often abbreviated EPSP.
See also Excitation, Synapse.
A set of mental skills for planning, focusing attention, switching between tasks and controlling impulses, relying heavily on the prefrontal cortex.
See also Prefrontal cortex.
A PCR primer whose sequence spans the junction between two exons, so that it binds only cDNA made from spliced mRNA and not genomic DNA, in which the exons are separated by an intron.
See also PCR primer, No-RT control, cDNA.
The extent to which a study’s result applies beyond the particular sample, setting and conditions studied, for example to other populations or species.
See also Internal validity, Construct validity.
The summed excitatory synaptic response of many neurons, recorded with an electrode placed in the tissue outside the cells, often in hippocampal slices. Its initial slope is used to measure synaptic strength. Often abbreviated fEPSP.
See also Excitatory postsynaptic potential, Long-term potentiation.
The set of an excitation filter, a dichroic mirror and an emission filter mounted together in a fluorescence microscope, chosen to suit one fluorophore.
See also Dichroic mirror, Excitation and emission spectra.
A test of association in a two-by-two table that calculates the p-value exactly from all the tables possible with the same row and column totals. It is used instead of the chi-squared test when expected counts are small.
See also Chi-squared test, Association.
A version of a gene in which an important section is flanked by two loxP sites. It works normally until Cre recombinase removes the section between them.
See also Cre recombinase, Knockout.
A molecule that absorbs light of one colour and gives out light of a longer wavelength, used to label structures for fluorescence microscopy.
See also Excitation and emission spectra, Photobleaching.
Functional MRI: a method that measures changes in blood oxygen to show which brain regions are more active during a task or at rest.
See also MRI.
Functional near-infrared spectroscopy: a method that passes near-infrared light through the scalp to measure changes in blood oxygen in the outer cortex.
See also fMRI.
In chromatin immunoprecipitation, the signal recovered with the specific antibody divided by that recovered with a control antibody, or by that at a region where the protein is not expected to bind.
See also Percent input, Isotype control.
An S-shaped curve, defined by a bottom, a top, a midpoint and a slope, that is fitted to the standards of an immunoassay or to a concentration–response experiment. It describes assays whose signal levels off at low and high concentrations better than a straight line does.
See also Standard curve, Concentration–response curve.
The front part of each cerebral hemisphere, involved in planning, decision-making, movement, speech production and self-control.
See also Prefrontal cortex, Motor cortex.
Gamma-aminobutyric acid, the main inhibitory neurotransmitter of the brain. It makes receiving neurons less likely to fire.
See also Inhibition, Interneuron.
A statistical framework that explains a measured signal as a weighted sum of predictors plus noise. In fMRI it is fitted to each voxel to estimate how strongly each condition drives the signal. Often abbreviated GLM.
See also Haemodynamic response function, Design efficiency.
A study that scans the genomes of many people to find common genetic variants linked to a trait or disease. Often abbreviated GWAS.
See also Heritability.
The particular versions of a gene, or genes, that an individual carries. In animal research it is usually determined from a small tissue sample by PCR.
Glial fibrillary acidic protein: a filament protein of astrocytes, used as a marker for them. Its levels rise when astrocytes become reactive after injury or in disease.
See also Astrocyte.
Any of the non-neuronal cells of the nervous system. Glia support, insulate, nourish and defend neurons, and help shape how they communicate.
See also Astrocyte, Oligodendrocyte, Microglia.
The main excitatory neurotransmitter of the brain. It makes receiving neurons more likely to fire and is central to learning and memory.
See also Excitation, Long-term potentiation.
A silver-based staining method, introduced by Camillo Golgi, that fills a small and apparently random fraction of neurons completely in black, showing their full cell bodies, dendrites and spines.
See also Dendritic spine, Spine density.
A protein, originally from the jellyfish Aequorea victoria, that glows green under blue light. Its gene can be introduced into cells to label them or fused to other proteins to show where they are.
See also Fluorophore, Transfection.
An adjustment to the degrees of freedom of a repeated-measures analysis of variance, used when the variances of the differences between conditions are unequal, an assumption known as sphericity.
See also P-value.
Brain and spinal cord tissue rich in neuron cell bodies, dendrites and synapses. It forms the cerebral cortex and deep nuclei such as the thalamus.
See also White matter, Cerebral cortex.
A layer at the top, and often the bottom, of a thick section that is excluded from counting in the optical disector because cutting can damage or remove cells at the surfaces.
See also Disector, Optical fractionator.
The short RNA that directs Cas9 to its target. About 20 of its bases match the DNA to be cut, and the choice of this sequence decides where, and how specifically, editing happens. Often abbreviated gRNA or sgRNA.
See also CRISPR–Cas9, Off-target effect.
A gyrus is a ridge on the surface of the brain and a sulcus the groove between two ridges. The folds let a large sheet of cortex fit inside the skull.
See also Cerebral cortex.
A thick glass slide with a counting chamber of known depth, engraved with a grid, used to count cells under a microscope and calculate their concentration in a suspension.
See also Trypan blue, Primary culture.
The typical time course of the fMRI signal after a brief burst of neural activity: a slow rise that peaks a few seconds later, roughly five, then falls back with a small undershoot. Often abbreviated HRF.
See also fMRI, General linear model.
The proportion of the variation in a trait within a population that is linked to genetic differences. It does not say how much of one person’s trait is caused by genes.
See also Genome-wide association study.
Carrying two different alleles of a gene, for example one normal and one modified copy.
See also Homozygous, Allele.
The genes whose expression varies most from cell to cell in a single-cell dataset, beyond what technical noise would produce. They are selected to focus later analysis on biologically informative differences.
See also Single-cell RNA sequencing, Principal component analysis.
A number describing how steep a concentration–response curve is. A value near one is expected for simple binding to a single site; steeper curves can indicate cooperativity.
See also Concentration–response curve, EC50.
A curved structure deep in the temporal lobe, essential for forming new memories of events and places. It is affected early in Alzheimer’s disease.
See also Long-term potentiation, Memory.
One of a family of small, positively charged proteins around which DNA is wound in the nucleus. Chemical marks added to their tails, such as acetyl or methyl groups, help to control gene activity.
See also Nucleosome, Histone acetylation, Chromatin.
The addition of acetyl groups to lysines in histone tails by histone acetyltransferases, reversed by histone deacetylases. It loosens chromatin and is associated with active promoters and enhancers; H3K27ac, acetylation of histone H3 at lysine 27, is a widely used example.
See also Histone, Chromatin immunoprecipitation.
Tissue broken up in buffer, for example with a glass–Teflon homogeniser, to make a uniform suspension. It is the starting material for subcellular fractionation.
See also Differential centrifugation, Lysate, Enrichment (subcellular).
Similarity between genes or proteins that results from descent from a common ancestral sequence. Sequences either are or are not homologous; percent identity measures how similar they are.
See also Orthologue, Paralogue, Sequence alignment.
A precise way of repairing a DNA break that copies a matching template. Supplying a designed template lets researchers insert or change specific bases after CRISPR cutting. Often abbreviated HDR.
See also Non-homologous end joining, CRISPR–Cas9.
Carrying two identical alleles of a gene, for example two modified copies.
See also Heterozygous, Allele.
A falsely low result in a one-step sandwich immunoassay when the analyte is so concentrated that it saturates both the capture and the detection antibodies separately, so that fewer sandwiches form. Diluting the sample reveals it.
See also ELISA, Standard curve.
A chemical messenger carried in the blood that acts on distant organs. The hypothalamus and pituitary gland link the brain to the hormone system.
See also Hypothalamus.
A gene needed for basic cell functions, and so expressed in most cells, such as GAPDH or ACTB. Housekeeping genes are often used as reference genes, although their expression can vary with tissue, age and treatment.
See also Reference gene, Loading control.
A small region below the thalamus that controls body temperature, hunger, thirst, sleep cycles and the hormone system through the pituitary gland.
See also Hormone, Circadian rhythm.
A protein found in microglia and macrophages, widely used as a marker to stain microglia and follow changes in their shape and number.
See also Microglia.
An intensity value chosen in image analysis so that pixels above it count as signal and pixels below it as background. The choice strongly affects measured areas and counts, so it should be set by a fixed rule and applied blind to group.
See also Signal saturation, Region of interest, Randomisation and blinding.
A gene that is switched on rapidly and briefly in response to a stimulus, without the need for new proteins to be made first. In neurons, strong activity triggers immediate early genes such as c-Fos.
See also c-Fos.
Immunostaining in which the antibodies carry fluorophores, so that labelled proteins glow in chosen colours under a fluorescence microscope.
See also Immunohistochemistry, Primary and secondary antibody.
Staining of tissue sections with antibodies that bind a chosen protein, so that its location can be seen under a microscope.
See also Microscopy.
Pulling a particular protein out of a mixture, such as a cell lysate, with an antibody attached to beads, so that it can be detected or studied.
See also Co-immunoprecipitation, Chromatin immunoprecipitation, Isotype control.
A method that detects a particular RNA or DNA sequence in cells or tissue sections with a labelled probe of complementary sequence, showing which cells express a gene and where. Fluorescent versions are called FISH.
See also Antisense probe, Branched-DNA amplification, Messenger RNA.
In vivo studies use living organisms; in vitro studies use cells or tissue in a dish; ex vivo studies use tissue taken from an organism; in silico studies are computer models.
See also Organoid.
A small insertion or deletion of bases in DNA. An indel whose length is not a multiple of three shifts the reading frame of a gene and usually disrupts the protein.
See also Non-homologous end joining, T7 endonuclease I assay.
A stem cell made by reprogramming an adult cell, such as a skin or blood cell, with a small set of genes so that it can become almost any cell type. Neurons made from a person’s induced pluripotent stem cells carry that person’s genome.
See also Primary culture, Organoid.
A synaptic signal that makes the receiving neuron less likely to fire. A balance of excitation and inhibition keeps brain activity stable.
See also GABA, Excitation.
A variable that affects the exposure, affects the outcome only through the exposure, and shares no causes with the outcome. Under these assumptions it can be used to estimate a causal effect despite unmeasured confounding.
See also Mendelian randomisation, Confounder, Natural experiment.
The extent to which a study’s result reflects a true effect in the sample studied, rather than bias, confounding or chance.
See also External validity, Construct validity, Confounder.
A neuron whose connections stay within a local circuit. Most interneurons of the cortex release GABA and keep excitation in check.
See also GABA, Inhibition.
A measure of how much of the total variation in measurements lies between groups or subjects rather than within them. It is used to assess agreement between repeated measurements or raters, and to show how alike observations from the same animal or culture are.
See also Pseudoreplication, Biological and technical replicates.
A protein pore in the cell membrane that lets particular ions, such as sodium, potassium, calcium or chloride, flow through when it opens.
See also Action potential, Receptor.
An ischaemic stroke happens when an artery to the brain is blocked; a haemorrhagic stroke happens when a blood vessel in or around the brain bursts.
See also Penumbra, Thrombectomy.
An antibody of the same species, class and subclass as the specific antibody but with no known target in the sample, used to measure binding that is not due to the antibody’s target.
See also Immunoprecipitation, Positive and negative controls, Fold enrichment.
A measure, τ (tau), of how consistently two variables rank observations in the same order, based on the numbers of pairs of observations that are ordered the same way and the opposite way on both variables.
See also Correlation, Spearman’s rank correlation.
An animal, or cell, in which a gene has been deliberately inactivated so that its role can be studied. In a conditional knockout the gene is removed only in chosen cells or at a chosen time.
See also Floxed allele, Cre recombinase.
A lasting change in behaviour or knowledge that results from experience.
See also Synaptic plasticity, Memory.
A loosely defined group of brain structures, including the hippocampus, amygdala and cingulate cortex, involved in emotion, motivation and memory.
See also Amygdala, Hippocampus.
The lowest amount of a substance that an assay can reliably distinguish from a blank sample, often estimated as the mean of blank readings plus three standard deviations.
See also Limit of quantification, Standard curve.
The lowest amount of a substance that an assay can measure with acceptable precision and accuracy. It is higher than the limit of detection; values below it can show that a substance is present but not reliably how much.
See also Limit of detection, Coefficient of variation.
Yellow-brown granules of oxidised fats and proteins that accumulate with age inside long-lived cells such as neurons. They fluoresce across a wide range of wavelengths and can be mistaken for real staining.
See also Autofluorescence, Sudan Black B, Neuromelanin.
A control animal from the same litter as the experimental animals, sharing their parents, age and rearing, so that differences are more likely to be due to genotype.
A protein expected to be equally abundant in every sample, such as actin or GAPDH, measured on a Western blot to check that equal amounts were loaded and to normalise the target signal.
See also Western blot, Densitometry.
A lasting increase in the strength of a synapse after strong, repeated activity, first described in the hippocampus. Often abbreviated LTP.
See also Synaptic plasticity, Hippocampus.
The liquid produced by breaking open cells or tissue, containing their proteins, nucleic acids and other contents.
See also Homogenate, Detergent, Protease inhibitor.
A test that compares two independent groups using the ranks of their values rather than the values themselves, so it does not assume normally distributed data. It asks whether values in one group tend to be larger than those in the other.
See also Welch’s t-test, P-value.
Microtubule-associated protein 2, found in the dendrites and cell bodies of neurons but largely absent from axons. Antibodies against it are used to identify neurons and to trace their dendrites.
See also Dendrite, NeuN, Sholl analysis.
A premixed solution containing the shared ingredients of a reaction, such as polymerase, nucleotides, buffer and magnesium, so that every tube receives the same amounts.
See also PCR.
Interference with an assay by other components of a sample, such as the proteins, lipids or salts of plasma or tissue lysate, so that the same amount of analyte gives a different signal from that in the standards.
See also Spike recovery, ELISA.
The strongest pulse a TMS stimulator can deliver. Intensities are given as a percentage of it, written %MSO, which varies between machines and coils.
See also Transcranial magnetic stimulation, Resting motor threshold.
A variable that lies on the causal path from an exposure to an outcome: the exposure changes the mediator, which in turn changes the outcome. Adjusting for a mediator removes part of the effect being studied.
See also Confounder, Moderator.
Magnetoencephalography: recording the weak magnetic fields produced by brain activity, with high temporal precision.
See also EEG.
A plot of fluorescence as PCR products are slowly heated at the end of a run with a DNA-binding dye. Each double-stranded product separates at its own melting temperature, so a single sharp peak suggests a single specific product.
See also Primer dimer, RT-qPCR, Amplicon.
The ability to encode, store and later recall information and experiences. Different kinds include working memory, memory for events and memory for skills.
See also Working memory, Hippocampus.
An instrumental-variable method that uses genetic variants known to affect an exposure to estimate the exposure’s causal effect on an outcome. Because alleles are allocated at conception, they are largely independent of later confounders, although a variant with other effects on the outcome can bias the result.
See also Instrumental variable, Genome-wide association study.
The proportions of offspring genotypes expected from a cross when alleles are inherited independently and all offspring survive, for example 1 : 2 : 1 from two heterozygous parents.
See also Heterozygous, Chi-squared test.
The three membranes, dura mater, arachnoid and pia mater, that wrap the brain and spinal cord.
See also Meningitis.
Inflammation of the meninges, usually caused by infection with bacteria or viruses. Bacterial meningitis is a medical emergency.
See also Meninges.
The RNA copy of a gene that carries its instructions from the DNA to the ribosomes, where they are translated into protein. Measuring a gene’s mRNA is a common way to estimate how strongly it is expressed.
See also Codon, cDNA, In situ hybridisation.
The resident immune cells of the brain and spinal cord. They clear debris and microbes, respond to damage and prune unneeded synapses during development.
See also Glial cell, Neuroinflammation.
The use of microscopes to see cells and their parts. Neuroscience uses light, fluorescence, two-photon and electron microscopy, among others.
See also Immunohistochemistry.
A common neurological condition with recurrent attacks of moderate or severe headache, often with nausea and sensitivity to light and sound.
See also Aura.
The Minimum Information for Publication of Quantitative Real-Time PCR Experiments: guidelines listing the details of samples, assays, controls and analysis that a qPCR study should report so that it can be judged and repeated. First published in 2009, they have since been revised.
See also RT-qPCR, Reference gene.
A variable that changes the size or direction of the effect of an exposure on an outcome, so that the effect differs between subgroups. Also called an effect modifier.
See also Mediator, Confounder.
The strip of cortex in the frontal lobe that sends commands for voluntary movement to the brainstem and spinal cord.
See also Motor neuron.
The electrical response recorded from a muscle, by electromyography, after stimulation of the motor cortex or its pathways, for example with TMS. Often abbreviated MEP.
See also Transcranial magnetic stimulation, Electromyography.
A neuron that carries commands to muscles. Upper motor neurons run from the brain to the spinal cord; lower motor neurons run from the spinal cord or brainstem to the muscles.
See also Spinal cord.
Magnetic resonance imaging: a scanner that uses a strong magnetic field and radio waves to make detailed pictures of the body without X-rays.
See also fMRI, Diffusion MRI.
An adjustment made when many statistical tests are run, because the chance of at least one false positive rises with the number of tests. Common methods include the Bonferroni and Holm corrections and control of the false discovery rate.
See also P-value.
A fatty insulating sheath wrapped around many axons. It speeds the conduction of nerve signals, which are regenerated only at gaps in the sheath called nodes of Ranvier.
See also Node of Ranvier, Demyelination.
A situation in which an exposure is allocated by events outside the researchers’ control, such as a policy change or a geographical boundary, in a way that is close to random, so that it can be studied almost as if it were an experiment.
See also Instrumental variable, Difference-in-differences, Regression discontinuity.
A protein in the nucleus of most mature neurons, widely used as an antibody marker to identify and count neurons. A few types, such as Purkinje cells, show little or none.
See also Neuron, Immunohistochemistry.
The progressive loss of the structure or function of neurons, the process behind diseases such as Alzheimer’s, Parkinson’s and Huntington’s disease.
See also Amyloid beta, Alpha-synuclein.
A condition that arises from differences in how the brain develops, such as autism, ADHD, intellectual disability and cerebral palsy.
See also Neurogenesis.
The birth of new neurons from stem or progenitor cells. It is extensive before birth; how much continues in the adult human brain is still debated.
See also Radial glia.
Inflammation within the brain or spinal cord, driven by microglia, astrocytes and immune cells, seen in infection, injury and many brain disorders.
See also Microglia.
A dark pigment that builds up with age in the dopamine and noradrenaline neurons of the substantia nigra and locus coeruleus, giving these regions their dark colour.
See also Substantia nigra, Dopamine, Lipofuscin.
A nerve cell: the cell that receives, processes and sends electrical and chemical signals. A typical neuron has a cell body, branching dendrites that collect inputs and a single axon that carries its output.
Damage to the peripheral nerves, causing numbness, tingling, pain or weakness, often first in the feet and hands.
See also Peripheral nervous system.
The nervous system’s ability to change its structure and function with experience, learning or injury, from single synapses to whole networks.
See also Synaptic plasticity.
A chemical messenger released by a neuron at a synapse that acts on receptors of the receiving cell. Examples include glutamate, GABA, dopamine, serotonin and acetylcholine.
A classic stain that marks cell bodies in nerve tissue, used to see how neurons are arranged in layers and nuclei.
See also Brain atlas.
A sample put through reverse transcription without the reverse transcriptase enzyme. Any signal it gives in the following PCR comes from contaminating genomic DNA rather than from RNA.
See also DNase I, No-template control, Exon–exon junction primer.
A PCR tube containing every ingredient except the DNA sample. A band in it means that something in the reaction is contaminated.
See also PCR, Positive and negative controls.
A short gap in the myelin along an axon, packed with ion channels, where the action potential is regenerated as it travels.
See also Myelin, Action potential.
The cell’s fast, error-prone way of rejoining a broken DNA double strand. It often adds or removes a few bases, which can disrupt a gene after CRISPR cutting. Often abbreviated NHEJ.
See also Indel, Homology-directed repair.
The basic repeating unit of chromatin: about 147 base pairs of DNA wrapped around a core of eight histone proteins, two each of H2A, H2B, H3 and H4.
A number describing the range of angles over which an objective lens collects light. A higher numerical aperture gathers more light and resolves finer detail.
See also Objective lens, Microscopy.
The lens of a microscope closest to the sample, which collects light and sets the magnification and much of the image quality.
See also Numerical aperture, Microscopy.
The back part of each hemisphere, which contains the visual cortex.
See also Visual cortex.
The odds of an outcome (or of an exposure) in one group divided by the odds in another. It is the usual measure of association in case–control studies and approximates the risk ratio when the outcome is rare.
See also Risk ratio, Case–control study.
An unintended edit at a site in the genome that resembles the intended target closely enough for the guide RNA to bind there.
See also Guide RNA.
A glial cell of the brain and spinal cord that wraps the axons of many neurons in myelin.
See also Myelin, Schwann cell.
A light-sensitive protein, such as channelrhodopsin or halorhodopsin, that can be expressed in chosen neurons so that light excites or silences them.
See also Optogenetics.
A stereological method for estimating the total number of cells in a region by counting them with optical disectors in a known fraction of the sections, of the area of each section and of its thickness, and multiplying the count by the inverse of those fractions.
See also Stereology, Disector, Counting frame.
A method that makes chosen neurons sensitive to light, so they can be switched on or off with millisecond precision.
See also Neuron.
A small, simplified three-dimensional tissue grown from stem cells in a dish, which can model aspects of a developing human brain.
See also Neurogenesis.
A number between zero and one describing how strongly a visual neuron prefers edges or gratings of one orientation over others. Values near one mean a sharply tuned cell. Often abbreviated OSI.
See also Visual cortex, Calcium imaging.
One of two or more genes in different species that descend from a single gene in their last common ancestor and were separated by speciation, such as the human and mouse versions of a gene.
The probability of obtaining a result at least as extreme as the one observed if there were no true effect. A small p-value suggests the data are unlikely under that assumption, but it does not give the size or importance of an effect.
See also Effect size, Multiple comparisons correction.
A positive event-related potential that peaks roughly 300 milliseconds or later after a rare or task-relevant stimulus, for example in an oddball task.
See also Event-related potential, EEG.
The size of the response to the second of two closely spaced stimuli divided by the size of the first. A ratio above one, called paired-pulse facilitation, generally suggests synapses with a low probability of transmitter release.
See also Synaptic plasticity, Field excitatory postsynaptic potential.
One of two or more genes that arose by duplication of a gene within a genome. Paralogues often take on related but distinct functions.
See also Orthologue, Homology.
The upper back part of each hemisphere, which processes touch and body position and helps with attention and spatial awareness.
See also Somatosensory cortex.
A technique that seals a fine glass pipette onto a cell membrane to record the currents through ion channels, or the voltage of a whole cell.
See also Ion channel, Electrophysiology.
The polymerase chain reaction: repeated cycles of heating and cooling in which a DNA polymerase copies a chosen stretch of DNA, doubling it roughly every cycle until there is enough to detect.
See also PCR primer, Master mix, Agarose gel.
A short, single-stranded piece of DNA that binds next to the target sequence and gives the polymerase a starting point. A pair of primers, forward and reverse, defines the stretch that PCR copies.
See also PCR.
A protein module of roughly 80 to 90 amino acids that binds short motifs at the very end of other proteins. Named after PSD-95, Dlg and ZO-1, it anchors receptors and channels to scaffold proteins at synapses.
See also Postsynaptic density, Co-immunoprecipitation.
A measure, r, of how closely paired measurements follow a straight line, ranging from −1 (a perfect negative line) through 0 (no linear relationship) to +1 (a perfect positive line). It is sensitive to outliers and misses curved relationships.
See also Correlation, Spearman’s rank correlation, Kendall’s rank correlation.
The zone of brain tissue around a stroke’s core that has too little blood to work but can still survive if blood flow is restored quickly.
See also Ischaemic and haemorrhagic stroke.
The amount of DNA or protein recovered by an immunoprecipitation expressed as a percentage of the amount in the input, a small portion of the starting material set aside before the antibody is added.
See also Fold enrichment, Chromatin immunoprecipitation, Co-immunoprecipitation.
The process by which the brain organises and interprets information from the senses into an experience of the world.
See also Sensory neuron.
All nerves and ganglia outside the brain and spinal cord, connecting them to the muscles, skin and organs.
See also Central nervous system, Neuropathy.
Positron emission tomography: an imaging method that uses a small amount of radioactive tracer to measure processes such as glucose use, or deposits of amyloid or tau.
See also Amyloid beta, Tau.
The gradual, permanent fading of a fluorophore as it is exposed to excitation light, which limits how long and how brightly a sample can be imaged.
See also Fluorophore.
A branching diagram that shows the inferred evolutionary relationships among genes or species, with branch points representing common ancestors.
See also Bootstrap (phylogenetics), Sequence alignment, Orthologue.
An inactive treatment made to look like the real one, given to a comparison group so that the effects of receiving a treatment, and of expecting to benefit, are the same in both groups.
See also Randomised controlled trial, Randomisation and blinding.
A synthetic, positively charged polymer used to coat glass and plastic so that negatively charged cell membranes, such as those of neurons, stick and grow on it. The D form resists breakdown by cellular enzymes.
See also Primary culture.
A positive control is a sample expected to give a result, showing that the method works; a negative control is one expected to give none, showing that a result is not produced by contamination or the method itself.
See also No-template control, Loading control.
The time between a person’s death and the preservation of their tissue, by freezing or fixation. Longer intervals can degrade RNA and proteins.
See also Brain bank, Agonal state, RNA integrity number.
A dense, protein-rich thickening under the postsynaptic membrane of excitatory synapses that holds glutamate receptors, scaffold proteins such as PSD-95 and signalling enzymes. Because it resists extraction with mild detergents, it can be isolated as a fraction.
See also Synapse, PDZ domain, Synaptosome.
Recording a study’s hypotheses, design and planned analyses in a public registry before the data are collected or analysed, so that planned and exploratory analyses can be told apart.
See also Replication (research), Multiple comparisons correction.
The front-most part of the frontal lobe, central to planning, working memory, decision-making and regulating emotion.
See also Executive function.
In indirect immunostaining, a primary antibody binds the target protein and a labelled secondary antibody, raised against antibodies of the primary’s host species, binds the primary and amplifies the signal.
See also Immunofluorescence, Immunohistochemistry.
Cells grown directly from tissue taken from an animal or person, rather than from a cell line that divides indefinitely. Primary neurons do not divide, so each culture lasts only a few weeks.
See also Trituration, Days in vitro, Poly-D-lysine.
A short, unwanted PCR product formed when two primers bind to each other and are extended. In quantitative PCR it adds signal unrelated to the target and shows as an extra, lower-temperature peak in the melt curve.
See also Melt curve, PCR primer, No-template control.
A method that summarises many correlated measurements with a smaller number of new axes, the principal components, that capture as much of the variation as possible. Often abbreviated PCA.
See also Highly variable genes, UMAP.
The stretch of DNA at the start of a gene where RNA polymerase and transcription factors assemble to begin transcription.
See also Transcription factor, CREB.
A substance that blocks enzymes that break down proteins. Mixtures of protease inhibitors are added to lysates and homogenates to stop the proteins of interest being degraded.
See also Lysate, Homogenate.
A short DNA sequence that must lie immediately next to the target site for Cas9 to bind and cut. For the commonly used Cas9 from Streptococcus pyogenes it is NGG. Often abbreviated PAM.
See also Guide RNA, CRISPR–Cas9.
An analysis that adds together the counts of all cells of one type from each sample, so that samples rather than cells are compared. It avoids treating cells from the same individual as independent.
See also Pseudoreplication, Single-cell RNA sequencing.
Treating measurements that are not independent, such as many cells from one animal, as if they were independent samples. It inflates the apparent sample size and makes false positives more likely.
See also Biological and technical replicates, Sample size.
A state in which a person loses some contact with reality, for example through hallucinations or delusions. It can occur in schizophrenia, bipolar disorder and other conditions.
See also Dopamine.
A free search engine, run by the US National Library of Medicine, for research articles in biomedicine and the life sciences.
A large neuron of the cerebellar cortex with a flat, fan-shaped dendritic tree. It is the only output neuron of the cerebellar cortex.
See also Cerebellum.
The main excitatory neuron of the cerebral cortex and hippocampus, with a triangular cell body, a long apical dendrite and an axon that projects to other regions.
See also Cerebral cortex.
In quantitative PCR, the cycle, often fractional, at which a sample’s fluorescence crosses a set threshold. A lower value means more starting template; at 100% efficiency a difference of one cycle is a two-fold difference. Abbreviated Cq; formerly called the threshold cycle, Ct.
See also RT-qPCR, Amplification efficiency, Delta-delta Cq method.
Elongated cells of the developing brain that act both as stem cells and as scaffolds along which newborn neurons migrate to their place in the cortex.
See also Neurogenesis, Cerebral cortex.
Randomisation assigns participants to groups by chance; blinding keeps participants or researchers unaware of the group. Both reduce bias in experiments and trials.
See also Clinical trial.
A study in which participants are allocated at random to receive an intervention or a comparison, such as a placebo or usual care. Random allocation balances known and unknown confounders between the groups on average.
See also Placebo, Randomisation and blinding, Clinical trial.
A distortion that arises when participants with and without an outcome remember or report past exposures differently, a particular risk in case–control studies.
See also Case–control study, Selection bias.
A protein that detects a specific signal, such as a neurotransmitter or hormone, and changes the cell’s activity in response. The word also names sensory cells that detect stimuli.
See also Neurotransmitter.
A gene measured alongside the target in RT-qPCR to correct for differences between samples in the amount and quality of RNA. A good reference gene must be shown not to change with the conditions being compared, and two or more are usually used.
See also Housekeeping gene, Delta-delta Cq method, Loading control.
The short time after an action potential during which a neuron cannot fire again, or needs a stronger stimulus to do so, because its sodium channels are recovering.
See also Action potential, Ion channel.
Two spikes assigned to the same neuron that are closer together than its refractory period allows, typically within a millisecond or two. Many such violations suggest that a sorted unit contains spikes from more than one cell.
See also Spike sorting, Refractory period.
An area of an image or scan, such as one cell body or one brain region, that is outlined so that its signal can be measured. Often abbreviated ROI.
See also Calcium imaging, Voxel.
A method for cases in which an exposure is given to everyone above a threshold on a continuous score. Comparing individuals just above and just below the threshold estimates the effect of the exposure at that point.
See also Natural experiment, Difference-in-differences.
The tendency of a measurement that is unusually high or low on one occasion to be closer to the average when it is measured again, purely because of random variation. It can make an untreated change look like the effect of a treatment.
See also Randomised controlled trial.
In MRI, the time between successive excitations of the same slice; in fMRI it is effectively the time taken to acquire one whole-brain volume. Often abbreviated TR.
Repeating a study with new data to see whether its finding holds. A direct replication repeats the original methods as closely as possible; a conceptual replication tests the same idea with different methods.
See also Pre-registration, Statistical power.
The voltage across a neuron’s membrane when it is not signalling, typically about −70 millivolts, inside negative relative to outside.
See also Action potential.
The lowest TMS intensity that produces small motor evoked potentials, conventionally about 50 microvolts, in about half of trials while the target muscle is relaxed. Other intensities are often set as a percentage of it. Often abbreviated RMT.
See also Motor evoked potential, Maximum stimulator output.
The smallest steady current that, injected for a long enough time, makes a neuron fire an action potential. It is a simple measure of how excitable a cell is.
See also Current clamp, Action potential.
The risk of an outcome in an exposed group divided by the risk in an unexposed group. A value of 1 means no association; a value of 2 means the outcome is twice as common in the exposed group.
See also Odds ratio, Cohort study.
A score from 1 (completely degraded) to 10 (intact) that summarises the quality of an RNA sample, calculated by software from the pattern of RNA sizes seen by capillary electrophoresis.
See also RNase, Post-mortem interval, Agonal state.
Ribonuclease: any enzyme that breaks down RNA. RNases are abundant and very stable, on skin and in most tissues, so RNA work relies on clean handling, RNase-free reagents and RNase inhibitors.
See also RNA integrity number, DNase I.
Reverse transcription quantitative PCR: RNA is first copied into cDNA by the enzyme reverse transcriptase, and the cDNA is then amplified by quantitative (real-time) PCR, in which fluorescence is read every cycle so that the starting amount can be estimated. Quantitative PCR (qPCR) on its own measures DNA, as in ChIP-qPCR.
See also cDNA, Quantification cycle, PCR.
The number of participants, animals or samples in a study. Too small a sample makes real effects easy to miss and chance findings easy to mistake for real ones.
See also Statistical power.
A method for characterising a competitive antagonist by measuring how far increasing concentrations of it shift the agonist’s concentration–response curve to the right. It yields an estimate of the antagonist’s affinity.
See also Antagonist, Concentration–response curve.
A glial cell of the peripheral nervous system that forms the myelin around a single segment of one axon and helps nerves regenerate after injury.
See also Myelin, Peripheral nervous system.
Sodium dodecyl sulphate polyacrylamide gel electrophoresis: proteins are coated with a detergent that unfolds them and gives them a negative charge, so that they separate by size in a gel.
See also Western blot, DNA ladder.
A burst of abnormal, excessive electrical activity in the brain that can change movement, sensation, awareness or behaviour for a short time.
See also Epilepsy.
A distortion that arises when the people, animals or samples included in a study, or kept in the analysis, differ systematically from the population of interest in a way related to the exposure and outcome.
See also Survivorship bias, Berkson’s bias, Collider.
A neuron that converts a stimulus, such as touch, light, sound or heat, into nerve signals and carries them towards the central nervous system.
See also Receptor.
An arrangement of two or more DNA, RNA or protein sequences in rows, with gaps inserted so that corresponding positions line up in columns. It is used to measure similarity and to infer which positions are related by descent.
See also Homology, Phylogenetic tree.
A neurotransmitter, also called 5-HT, involved in mood, sleep, appetite and many other functions. Several antidepressants act on serotonin signalling.
See also Neurotransmitter.
A way of describing how a neuron’s dendrites branch by drawing circles of increasing radius around the cell body and counting how many times the dendrites cross each circle.
A paired-pulse TMS measure in which a weak conditioning pulse a few milliseconds before a stronger test pulse reduces the motor evoked potential. It is thought to reflect GABA-mediated inhibition within the motor cortex. Often abbreviated SICI.
See also Motor evoked potential, GABA.
The point at which a detector, such as a camera pixel, has reached its maximum value and records no further increase in signal. Saturated bands or pixels underestimate the true amount, so images for quantification should be acquired below saturation.
See also Densitometry, Western blot, Image threshold.
The reversal, appearance or disappearance of an association when groups are combined, compared with the association seen within each group. It usually arises because a third variable is related to both the grouping and the outcome.
See also Confounder, Association.
A method that measures which genes are being expressed in thousands of individual cells at once, so that cell types and states can be identified. Often abbreviated scRNA-seq.
See also Unique molecular identifier, Highly variable genes.
Recording the action potentials of individual neurons with an electrode placed in or near the tissue, as opposed to recording the combined activity of many cells.
See also Spike sorting, Electrophysiology.
A recurring state of reduced awareness and movement, with stages including rapid eye movement (REM) sleep and deep non-REM sleep, important for memory and health.
See also Circadian rhythm, Brain rhythm.
The strip of cortex in the parietal lobe that receives touch, pain, temperature and body-position information from the body.
See also Parietal lobe.
Breaking up material with high-frequency sound waves. In chromatin immunoprecipitation it shears chromatin into fragments a few hundred base pairs long, which sets how precisely a binding site can be located.
See also Chromatin immunoprecipitation, Crosslinking.
A measure, ρ (rho), of how consistently one variable rises or falls as another rises, whether or not in a straight line. It is Pearson’s correlation coefficient calculated on the ranks of the values.
See also Correlation, Pearson’s correlation coefficient, Kendall’s rank correlation.
A check for matrix effects in which a known amount of the pure analyte is added to a sample and the proportion of it measured by the assay is calculated; recoveries far from 100% show interference.
See also Matrix effect, ELISA.
The process of assigning spikes recorded on an extracellular electrode to the individual neurons that produced them, using the shape and size of each waveform.
See also Single-unit recording, Refractory period violation.
The column of nerve tissue running down the spine from the brainstem. It carries signals between brain and body and contains circuits for reflexes and walking.
See also Central nervous system.
The number of dendritic spines per unit length of dendrite, often given per 10 micrometres. It is used as an estimate of the number of excitatory synapses a neuron receives.
See also Dendritic spine, Golgi stain.
The relationship between signal and amount measured for standards of known concentration, run alongside the samples. The concentration of each unknown sample is read from the curve.
See also Four-parameter logistic fit, BCA assay, Amplification efficiency.
The probability that a study will detect an effect of a given size if the effect is real. It depends on sample size, effect size and variability.
See also Sample size.
A set of methods for estimating the number, length, area or volume of structures in three-dimensional tissue from systematically sampled sections, without assumptions about their shape, size or orientation.
See also Optical fractionator, Disector, Systematic uniform random sampling.
The difference between the peak wavelengths of a fluorophore’s excitation and emission. Because emitted light has a longer wavelength, filters can separate it from the light used to excite.
See also Excitation and emission spectra.
A dark-pigmented region of the midbrain whose dopamine neurons supply the basal ganglia. Their loss causes the movement symptoms of Parkinson’s disease.
See also Dopamine, Basal ganglia.
A column of sucrose solutions of increasing concentration through which particles are centrifuged, so that they collect in layers according to their density.
See also Differential centrifugation, Synaptosome.
A dark, fat-soluble dye applied to tissue sections to reduce autofluorescence from lipofuscin, at the cost of some added background, particularly at far-red wavelengths.
See also Lipofuscin, Autofluorescence.
Laminae I and II, the outermost layers of the dorsal horn of the spinal cord, which receive input from thin sensory fibres carrying pain, temperature and itch signals.
See also Spinal cord, Sensory neuron.
A form of selection bias that arises when only the individuals or items that passed some selection process, such as surviving or being published, are studied, so that those that did not are overlooked.
See also Selection bias.
The junction where one neuron passes a signal to another cell. At most synapses a chemical messenger is released across a narrow gap and detected by receptors on the other side.
See also Neurotransmitter, Synaptic cleft.
The narrow gap, roughly 20 to 40 nanometres wide, between the sending and receiving sides of a chemical synapse.
See also Synapse.
Lasting changes in the strength of synapses with use. It is thought to be a main way that memories are stored.
See also Long-term potentiation, Neuroplasticity.
A sealed nerve terminal, often with a piece of the postsynaptic membrane still attached, formed when brain tissue is gently homogenised and purified by centrifugation. Synaptosomes keep much of their machinery for taking up and releasing neurotransmitters.
See also Postsynaptic density, Differential centrifugation, Synapse.
A change in a DNA sequence that alters a codon without changing the amino acid it encodes, because of the redundancy of the genetic code. Comparing synonymous and non-synonymous rates (dN/dS) indicates how strongly selection acts on a protein.
See also Codon, Sequence alignment.
Sampling in which the first location is chosen at random and the rest follow at a fixed interval, so that every part of the structure has the same chance of being sampled. It is more efficient than independent random sampling.
See also Stereology, Optical fractionator.
A rapid test for CRISPR editing. The target region is amplified by PCR, melted and re-annealed, and the enzyme cuts where edited and unedited strands pair imperfectly; the cut fragments are seen on a gel.
See also Indel, Agarose gel.
A protein that normally stabilises the internal skeleton of axons. In Alzheimer’s disease and some other conditions it forms tangles inside neurons.
See also Amyloid beta.
A standard brain image, often an average of many scans such as the MNI template, onto which individual scans are aligned for comparison.
See also Brain atlas.
The lower side part of each hemisphere, involved in hearing, language, memory and recognising objects and faces.
See also Hippocampus.
A pair of egg-shaped structures in the centre of the brain that relay and filter information travelling to the cortex, including almost all senses.
See also Cerebral cortex.
Removal of a blood clot from a large artery with a device threaded through the blood vessels, used in some ischaemic strokes.
See also Thrombolysis.
Treatment with a clot-dissolving medicine to restore blood flow, used within hours of an ischaemic stroke in suitable patients.
See also Thrombectomy.
Treating tissue with a chemical such as paraformaldehyde that cross-links proteins, preserving its structure for sectioning and staining.
See also Transcardial perfusion, Immunohistochemistry.
Reconstruction of white-matter pathways from diffusion MRI, shown as bundles of lines through the brain.
See also Diffusion MRI, Connectome.
Pumping fluid through the heart of a deeply anaesthetised animal to wash out the blood and then deliver fixative evenly through its blood vessels, preserving the brain for staining.
See also Tissue fixation.
A non-invasive method in which a brief magnetic pulse from a coil held over the scalp induces electrical currents in the underlying cortex. Over the motor cortex it can make a muscle twitch. Often abbreviated TMS.
See also Motor evoked potential, Motor cortex.
A protein that binds specific short DNA sequences, usually in promoters or enhancers, and increases or decreases the transcription of nearby genes.
See also Promoter (gene), CREB, Chromatin immunoprecipitation.
Introducing DNA or RNA into cells by non-viral means, such as lipid particles, electroporation or calcium phosphate. Delivery with a virus is usually called transduction.
See also Green fluorescent protein, Primary culture.
A brief episode of stroke-like symptoms that resolves, usually within minutes to hours, without lasting damage. It is a warning sign of a possible stroke. Often abbreviated TIA.
See also Ischaemic and haemorrhagic stroke.
A widely used mild, non-ionic detergent that dissolves most membranes while leaving many protein complexes intact.
See also Detergent, Postsynaptic density.
Gently drawing tissue up and down through a pipette to break it into single cells, usually after digestion with an enzyme.
See also Primary culture.
A blue dye that cannot cross the intact membrane of a living cell, so that only dead cells take it up. It is used to count the living cells in a suspension.
See also Haemocytometer, Primary culture.
A fluorescence microscopy method in which a fluorophore is excited by two infrared photons arriving almost together. Excitation is confined to the focal point, which allows sharp imaging deep within living tissue.
See also Microscopy, Calcium imaging.
The enzyme that carries out the first, rate-limiting step in making dopamine and noradrenaline. Staining for it marks dopamine and noradrenaline neurons and their axons.
See also Dopamine, Substantia nigra.
Uniform manifold approximation and projection: a method for drawing high-dimensional data, such as single-cell profiles, as a two-dimensional map in which similar cells sit close together. Distances between distant clusters should not be over-interpreted.
See also Principal component analysis, Single-cell RNA sequencing.
A short random barcode attached to each RNA molecule before amplification, so that copies made during amplification can be recognised and the original molecules counted. Often abbreviated UMI.
See also Single-cell RNA sequencing.
A control treated with the solvent or carrier in which a drug is dissolved, at the same concentration, but without the drug, so that any effect of the solvent itself is accounted for.
See also Positive and negative controls, Randomisation and blinding.
Four connected fluid-filled cavities inside the brain that produce and hold cerebrospinal fluid.
See also Cerebrospinal fluid.
Thin slices of tissue for staining. A vibratome cuts fresh or fixed tissue with a vibrating blade; a cryostat cuts frozen tissue in a chilled chamber.
See also Tissue fixation, Immunohistochemistry.
The areas of the occipital lobe, and beyond, that process visual information arriving from the eyes through the thalamus.
See also Occipital lobe.
A recording mode in which the membrane voltage of a cell is held at a chosen value while the current needed to hold it is measured, revealing the currents that flow through ion channels.
See also Patch clamp, Current clamp.
A three-dimensional pixel: the smallest box of volume in a brain scan.
See also MRI.
A version of the t-test that compares the means of two groups without assuming that the groups have equal variances. It is often recommended as the default two-group test.
See also P-value, Effect size.
A method in which proteins are separated by size on a gel, transferred to a membrane and detected with antibodies, showing whether a protein is present and roughly how much there is.
See also SDS-PAGE, Loading control, Densitometry.
Brain and spinal cord tissue made mostly of myelinated axons, the long-distance connections between regions. It looks pale because of its myelin.
See also Myelin, Tractography.
The normal, unmodified form of a gene or animal, used as the comparison for animals carrying a mutation.
See also Allele, Littermate control.
Holding and using a small amount of information in mind for a few seconds, such as a phone number while dialling it.
See also Prefrontal cortex.
A series of images of the same field taken at regularly spaced focal depths, which together record a three-dimensional volume of the specimen.
See also Objective lens, Two-photon microscopy.
A measure of assay quality that compares the separation between positive and negative controls with their variability. Values above about 0.5 are usually taken to indicate an assay robust enough for screening.
See also Positive and negative controls.
The change in fluorescence divided by the baseline fluorescence, used to express calcium-imaging signals as a relative change that can be compared between cells.
See also Calcium imaging, Region of interest.
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