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Animals are multicellular organisms with eukaryotic cellular organization. A representative animal cell has a cell membrane, cell nucleus and mitochondria, but no cell wall or chloroplasts. A neuron illustrates how this common plan can acquire a specialized shape and signaling function. See OpenStax Biology 2e, 4.3: animal cell organization.

The axon initial segment is the specialized proximal region of an axon near the soma. In many neurons, its voltage-gated ion channels make it the site where an action potential begins. ^[ref]

Biology studies living systems: how biological cells maintain themselves, how organisms develop and reproduce, and how evolution generates diversity. Its scales connect molecules, genes, biological cells, organisms and the interactions studied by ecology. These are complementary viewpoints: a protein's chemistry can explain a cellular mechanism, while evolution explains why inherited variants of that mechanism persist. See Clark, Douglas and Choi, Biology 2e: the science of biology.

Two organizing ideas make this immense subject navigable: shared cellular organization and descent with inherited modification. A neuron and a gliding bacterium differ dramatically in shape and behavior, yet both depend on a cell membrane and metabolism. Their differences become intelligible through specialization and evolution.

Keep observations separate from the mathematical models used to explain them. A measured membrane potential is evidence; an idealized two-state ion-channel gating equation proposes a mechanism. A mathematical model earns trust through predictions and comparisons with measurements. Its assumptions delimit its usefulness, and disagreement can reveal missing biology rather than a faulty measurement.

A group of neurons whose coordinated activity and learned interactions can represent or participate in an experience. An assembly can overlap with assemblies for other events; it need not assign one private neuron to each memory.

Cell differentiation is the acquisition of a specialized cell state, involving changes in structure, function and gene expression. A neuron and a red blood cell illustrate different outcomes: signaling and oxygen transport. Different functions usually do not require a different inherited DNA sequence for each function. The shared-genome principle concerns nucleated precursors and most nucleated descendants: a mature mammalian red blood cell has lost its cell nucleus and mitochondria, so it is not an example of two mature biological cells both retaining the same nuclear DNA. ^[ref]

The puzzle is how a shared set of genes supports different jobs. Gene expression changes which RNA and proteins a biological cell produces, and in what amounts. A transcription factor can regulate several genes; different combinations of regulators can interpret the same signal differently. Stable regulatory patterns can persist through the cell cycle, providing memory of developmental history. Specialization therefore usually changes use of inherited information, rather than replacing the genome wholesale. ^[ref]

A small counting example separates sequence from activity. Suppose the same three toy genes are present in every nucleated biological cell, and independently assign each gene an on/off state. There are $2^3=8$ possible expression profiles with no DNA replacement. The figure shows only two: H and A on versus H and B on. Real gene expression is graded and coordinated, so this count illustrates possible descriptions, not a prediction of eight actual cell types. The interesting consequence is that a stable cell state can depend on how a shared record is used.

Stem cells combine self-renewal with production of differentiated descendants; progenitor cells generally have more restricted developmental options and renewal capacity. Neither term means that a biological cell must give rise to every cell type. Terminal differentiation denotes advanced specialization within a lineage, often accompanied by exit from the cell cycle. Cell fate concerns the developmental outcome of a biological cell or its descendants, whereas cell state describes its current properties. A temporary change in gene expression after signal transduction is not, by itself, proof of a new cell fate. ^[ref]

The brain and spinal cord, including both neurons and glial cells.

A chemical synapse transmits a signal by releasing neurotransmitter from a presynaptic neuron to act on postsynaptic receptors across a synaptic cleft. The two cell membranes remain separate. A typical fast transmission sequence is:

See Chemical Synapses and 3.1 Synapses. The fast pathway uses synaptic vesicles prepared near release sites; it does not require a distant synaptic vesicle to travel across the terminal after every action potential. See Basic Neurochemistry: calcium entry and vesicles at release sites. Some chemical synapses release neurotransmitter in response to graded presynaptic membrane potential changes rather than action potentials.

Neurotransmitter clearance limits how long released neurotransmitter remains available. Depending on the neurotransmitter and location, diffusion away, uptake through membrane transport proteins into the sending or neighboring biological cells, and breakdown by enzymes contribute. Receptor binding and unbinding also affect response duration. Recovering synaptic vesicle membrane is a separate recycling task; uptake of released neurotransmitter is not the return of an intact synaptic vesicle. See General Principles of Cell Communication.

This electrical-to-chemical-to-electrical sequence offers several places to adjust a signal: synaptic release probability, receptor availability and neurotransmitter clearance can change its strength or duration. It helps explain why synaptic plasticity can modify communication between neurons, and why an arriving action potential need not cause a postsynaptic action potential.

Otto Loewi's 1936 Nobel lecture describes his 1921 experiment: fluid from a frog heart whose nerves had been stimulated produced the corresponding response when transferred to another heart. The transferable substance established chemical mediation in that preparation. This was evidence for released chemical signaling, not yet an identification of synaptic vesicle fusion and not a claim that every synapse is chemical. See Loewi, The Chemical Transmission of Nerve Action, Nobel lecture, 12 December 1936.

Neuron 35, 783–792. Colored-filter exposure over days and persistence of unique-yellow shifts for one to two weeks. Author manuscript: www.neitzvision.com/research/publications/publications/2002-Neitz-Color_perception_mediated_by_plasticity-Neuron.pdf.

A compound action potential is an extracellularly recorded sum of activity from multiple axons. Amplitude and waveform depend on recruitment and relative arrival times. The documented neuronal paired-pulse recovery experiment illustrates why recovery of a summed response is not recovery of one neuron.

A receptor catch change expressed relative to a positive adapted-background catch. The same absolute increment can represent different contrasts on different backgrounds. These coordinates are useful for isolating signals without asserting that all neurons explicitly divide in this way.

Release or signalling by more than one transmitter from a neuron or pathway. Manipulating a cell identified by one transmitter can therefore change other signals as well.

Current clamp prescribes injected electric current while recording membrane potential. A constant command does not force membrane potential to remain constant: a neuron can produce action potentials or synaptic potentials while that command is unchanged. At zero commanded electric current, the amplifier still measures membrane potential; intrinsic ionic electric currents continue. The name concerns current supplied by the instrument, not the cancellation of all currents in the biological cell.

In whole-cell recording, the measured pipette voltage during a current pulse includes the patch-clamp series resistance drop. A modern authored methods article explicitly describes current-pulse protocols and this distortion.^[ref] Check the access contribution with small pulses and distinguish the immediate pipette-voltage jump from the slower membrane capacitance response. A zero-input interval measures a baseline, not proof that the instrument has no voltage offset. The passive example below explains these distinctions without asserting any new physiological measurements.

A neurotransmitter involved in multiple neural functions. Some phasic dopamine-neuron responses are consistent with reward-prediction-error signalling, and timed interventions can affect learning. This does not mean that every dopamine neuron or every timescale carries one identical scalar error.^[ref]

A brainstem nucleus containing many serotonin-releasing neurons. In stress-controllability experiments its activity depends on network regulation, illustrating why global transmitter amount alone is an inadequate account of behaviour.

A color-responsive neuron with opposite chromatic tuning in different spatial subregions. A simple filter is $r=(c_L-c_M{)}_{\mathrm{center}}-(c_L-c_M{)}_{\mathrm{surround}}$. It cancels a spatially uniform opponent signal but responds when the regions differ. Such filtering can support chromatic boundaries without by itself solving every illumination ambiguity.

An electrical synapse passes ionic electric current directly between neurons through gap junctions, whose paired channels connect the two cytoplasms. It does not require synaptic vesicle release and postsynaptic neurotransmitter binding. Transmission across the junction is very fast; the receiving cell membrane's capacitance and other conductances still determine its voltage response. Electrical coupling can coordinate the timing of activity across neurons. See Purves and colleagues: electrical synapses and gap junctions.

For a passive junction with constant conductance $g_j$, the inward electric current into cell 2 iswhere each $V_k$ is the cell's membrane potential, measured against a common extracellular reference. Taking $g_j=2\mathrm{nS}$, $V_1=-55\mathrm{mV}$ and $V_2=-65\mathrm{mV}$ gives $20\mathrm{pA}$ into cell 2 and the equal opposite electric current into cell 1. Exchanging the voltages reverses the electric current. Both depolarization and hyperpolarization can therefore be transmitted; an electrical synapse is not inherently an excitatory connection.

Many electrical synapses conduct in both directions, but this does not guarantee equal voltage responses: the cells can have different effective electrical resistance and capacitance. Some junctions rectify, meaning they conduct preferentially in one direction, so the constant-$g_j$ formula is insufficient. A concrete molecular example is the original study ^[ref]. Bidirectionality is thus a common property with important qualifications, rather than part of the definition.

An excitatory postsynaptic potential is a synaptic potential associated with increased likelihood of a postsynaptic action potential. Its size and effect depend on the receiving neuron's state; the definition concerns firing, not a fixed neurotransmitter identity. See synaptic potential for the mechanism and source.

Extracellular single-unit recording uses an electrode outside a neuron to detect electrical events attributed to that unit's action potentials. It records a spike train, not the intracellular membrane potential or every input synapse. ^[ref]

A major transmitter commonly associated with inhibitory signalling through appropriate receptors. Its cellular effect depends on receptor and ionic conditions; suppressing an inhibitory neuron can disinhibit its targets.

Primary publication: doi.org/10.1152/jn.90941.2008

Original article or primary record: pmc.ncbi.nlm.nih.gov/articles/PMC2712272/

Journal of Neurophysiology 102, 614–635; temporal latent model and 61 simultaneously recorded macaque premotor/motor neurons.