Synapse

A synapse is a signaling junction between a neuron and another biological cell. The sending side is presynaptic and the receiving side postsynaptic. At a chemical synapse, released neurotransmitter acts on a receptor in the receiving cell membrane. At an electrical synapse, gap junctions provide a direct path for electric current between cells. See 1.1 Elements of Neuronal Systems.

In a common sequence at a chemical synapse, an arriving action potential opens voltage-gated ion channels selective for calcium. Calcium entry triggers fusion of synaptic vesicles with the presynaptic cell membrane, releasing neurotransmitter into the synaptic cleft. Binding to a receptor changes postsynaptic electrical resistance and conductance, directly through an ion channel or through an intracellular signaling pathway. The resulting change in membrane potential is a synaptic potential. See Ion Channels and the Electrical Properties of Membranes.

A useful conductance approximation writes the inward-positive synaptic electric current aswhere $g_{\mathrm{syn}}\ge 0$ describes the activated electrical resistance and conductance, $V$ is the postsynaptic membrane potential, and $E_{\mathrm{syn}}$ is the reversal potential, the voltage at which this current vanishes. Opening these channels tends to pull $V$ toward $E_{\mathrm{syn}}$; it does not prescribe a current of fixed sign independently of $V$.

For a worked example, let $V=-65\mathrm{mV}$ and $g_{\mathrm{syn}}=1\mathrm{nS}$. A reversal potential of $0\mathrm{mV}$ gives $I_{\mathrm{syn}}=65\mathrm{pA}$, an inward electric current that raises membrane potential. A reversal potential of $-75\mathrm{mV}$ instead gives $-10\mathrm{pA}$, which lowers membrane potential. These are illustrative calculations, not measurements. A reversal potential of $-60\mathrm{mV}$ can raise $V$ from $-65\mathrm{mV}$ yet oppose reaching a threshold of $-50\mathrm{mV}$: a depolarizing input need not be excitatory.

An excitatory synapse favors a subsequent action potential, whereas an inhibitory synapse opposes it. The effect depends on the receptor, the permeating ions, their gradients and the reversal potential; a neurotransmitter does not have one fixed excitatory or inhibitory sign in every context. Even with $E_{\mathrm{syn}}=V$, an added conductance can reduce responses to other inputs by lowering effective electrical resistance, an effect called shunting inhibition. See Purves and colleagues: excitatory and inhibitory postsynaptic potentials. This dependence matters when translating a biological synapse into a signed weight or an imposed electric current in computational neuroscience.

Changes in synaptic efficacy over time. Activity-dependent plasticity can support learning and development, but also requires constraints to prevent unbounded growth or competition in simplified models.

A decaying record of recent activity that marks a state or connection as eligible for modification by a later teaching signal. An accumulating value-learning trace is $e_t=\gamma \lambda e_{t-1}+x(s_t)$, giving $\Delta w=\alpha {\delta }_t{e}_t$. Other traces record action-policy gradients or pre/post synaptic events. The update and episode-boundary convention must be specified; an eligibility trace is not automatically identical to the visual activity trace used for trace learning.

A persistent increase in synaptic efficacy induced by an appropriate pattern of activity. Its presence is a possible storage mechanism; a memory model must still explain which inputs are modified, the learning conditions and how subsequent activity retrieves the stored information.

Short-lived changes in synaptic efficacy dependent on recent activity, including facilitation and depression. Such changes can alter a network's response to a later input even when its immediately recorded activity does not reveal the retained information.

Constraints or interactions make the strengthening of some inputs limit others. In developmental models, competition together with input correlations can segregate ON and OFF subregions or inputs from the two eyes; correlations alone do not specify the full biological developmental mechanism.

A learning rule can constrain the sum or norm of incoming synaptic weights to prevent unbounded Hebbian learning. For ${\sum }_i{w}_{ai}=S$, subtracting the mean unconstrained update from each update preserves the sum. Bounds and renormalization may also be needed to keep excitatory weights nonnegative. Normalization of learning weights is distinct from divisive gain control in instantaneous neural responses.

A chemical signal released by a neuron that changes a target cell's activity through its receptors. Its effect depends on the receptor and ionic mechanism rather than being intrinsically excitatory or inhibitory in every context.

A peptide used in neural signalling. Release, receptor distribution and interactions with other transmitters affect its function.

A peptide signal involved in endocrine and neural stress regulation. Its actions within a defined local circuit need not match a whole-organism hormone concentration.

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.

Regulation of neural processing by chemical signals that can alter excitability, plasticity, gain or network state. Effects depend on receptor, target and timescale rather than only transmitter identity.

Observations establish what signals naturally covary with defined events; interventions estimate consequences of changing a specified target. Convergence requires matching cell population, projection, timescale and behavioural endpoint, with direct target engagement measurements and controls for off-target drug effects.

A signal acting in neuromodulation. The same molecule can have different functions at different receptors and targets; the label does not imply slow action or a single diffuse behavioural purpose.

A catecholamine transmitter involved in arousal, attention and other state-dependent functions, also called noradrenaline.

A monoamine transmitter also called 5-hydroxytryptamine. Distinct receptors and circuits can have different effects; blood levels are not a direct reading of synaptic transmission in the brain.

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 subtype of receptor for dopamine involved in neural signalling and targeted by many antipsychotic medications. Receptor blockade is a pharmacological action, not a complete psychological description of treatment response.

Acetylcholine is a neurotransmitter that acts through nicotinic ionotropic receptors and muscarinic metabotropic receptors. The receptor and the target cell's machinery determine the response; acetylcholine itself does not specify whether coupling is direct or mediated by intracellular signal transduction. ^[ref]

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.

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.

Neurotransmitter clearance removes released neurotransmitter from the region where it can activate receptors, through diffusion, cellular uptake or enzyme-mediated breakdown. Its routes and rates help delimit a chemical synapse's response in space and time; see the mechanisms and source under chemical synapse.

The synaptic cleft is the extracellular gap between the sending and receiving cell membranes of a chemical synapse. Released neurotransmitter crosses this gap to reach a receptor. ^[ref]

A synaptic vesicle is a small membrane-bounded compartment in a presynaptic terminal that stores neurotransmitter for release. Fusion with the cell membrane exposes its contents to the synaptic cleft; the packet supplied by one synaptic vesicle is a quantum of release. Quantal neurotransmitter release refers to these discrete packets, rather than the release of one molecule at a time. The postsynaptic response to a packet can vary with its contents, receptors and recording conditions. See Purves and colleagues: vesicles as the source of transmitter quanta.

The useful cycle is filling, preparation for fusion, calcium-triggered exocytosis, and recovery of membrane and proteins through endocytosis for reuse. Different recovery routes occur; recycling need not preserve a particular synaptic vesicle as an identifiable container throughout. Limited availability of prepared synaptic vesicles can reduce release during repeated stimulation, while changes in synaptic release probability can also change successive responses. See Basic Neurochemistry: secretion machinery and vesicle reuse and 3.1 Synapses.

For an illustrative calculation, assume four release sites, each with one prepared synaptic vesicle, each releasing with synaptic release probability $p=0.25$ during one presynaptic action potential. Assume independent Bernoulli trials and at most one release per site. The released packet count $K$ has a binomial distribution:The probability of no release is $\mathbb{P}(K=0)=0.75^4=0.31640625$; at least one release has probability $0.68359375$. An expected value of one packet does not mean that every action potential releases one packet. If each packet contributes a stipulated $0.5\mathrm{nS}$ conductance increment and increments add, the expected value of that increment is $0.5\mathrm{nS}$, with zero increment on about $31.6\%$ of trials. These assumptions are a teaching model: shared calcium fluctuations, unequal sites, depletion and nonlinear receptor responses can invalidate them.

Quantal neurotransmitter release is release of neurotransmitter in discrete packets associated with individual synaptic vesicles. Packet count and postsynaptic packet response are different quantities; see the binomial distribution example under synaptic vesicle.

Synaptic release probability is the probability of release at a specified site during a specified opportunity, such as one presynaptic action potential. It depends on the site's state and conditions; it is not the probability that the receiving neuron fires. In the example under synaptic vesicle, $p$ refers to one available site, whereas $1-(1-p{)}^4$ refers to any of four independent sites releasing.

Shunting inhibition is suppression of another input's effect through increased synaptic conductance: opening additional ion channels lowers effective electrical resistance, reducing the voltage response to a given added electric current. When the added reversal potential equals the resting membrane potential, there can be no voltage change at rest and still be inhibition of a simultaneous input. See 1.4 Limitations of the Leaky Integrate-and-Fire Model.

Use the passive synaptic potential model below with leak $g_L=10\mathrm{nS}$, $E_L=-65\mathrm{mV}$ and capacitance $C=200\mathrm{pF}$. A sustained inward test electric current of $I_{\mathrm{ext}}=100\mathrm{pA}$ alone gives a steady voltage increase of $I_{\mathrm{ext}}/g_L=10\mathrm{mV}$, so $V_{\infty }=-55\mathrm{mV}$. Effective electrical resistance is $100\mathrm{M\Omega }$ and the time constant is $20\mathrm{ms}$.

Now hold a shunting conductance $g_i=20\mathrm{nS}$ open with $E_i=E_L=-65\mathrm{mV}$. With no test electric current, rest stays at $-65\mathrm{mV}$. With the same $100\mathrm{pA}$ test electric current, total conductance becomes $30\mathrm{nS}$, so the steady voltage increase is only $100/30\simeq 3.333\mathrm{mV}$: $V_{\infty }\simeq -61.667\mathrm{mV}$. Effective electrical resistance is $33.333\mathrm{M\Omega }$ and the time constant is $200/30\simeq 6.667\mathrm{ms}$. A faster response can therefore be smaller. At the original rest the shunting electric current is zero; at $V=-55\mathrm{mV}$ it is $20(-65+55)=-200\mathrm{pA}$, opposing the voltage excursion.

The factor of three reduction applies to this constant-electric current, constant-conductance example. A finite pulse, conductance-driven input or spatially extended dendrite need not have the same reduction. The interesting feature is conditional action: the shunt can leave a quiet neuron's voltage unchanged yet reshape its response when another input arrives. A model that represents all inhibition as a fixed outward electric current misses this behavior.

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.

A synaptic potential is a postsynaptic change in membrane potential caused by activity at a synapse. Unlike the regenerative action potential, a passive synaptic potential is graded: its size depends on input strength, the initial membrane potential and the receiving cell membrane's properties. Local voltage changes can decay before reaching the soma; their timing and overlap help determine whether an action potential follows. See Ion Channels and the Electrical Properties of Membranes.

Depolarization means that the interior becomes less negative relative to the exterior; hyperpolarization means that it becomes more negative. Excitation and inhibition instead describe whether an input promotes or opposes postsynaptic action potential generation. An inhibitory postsynaptic potential can be depolarizing, and shunting inhibition can occur with no voltage change at rest. The receptor, permeating ions, ionic gradients and reversal potential matter. See Purves and colleagues: excitation, inhibition and depolarizing inhibition.

A worked passive model treats the receiving membrane as one compartment with capacitance $C>0$, leak conductance $g_L>0$, and activated synaptic conductances $g_e,g_i\ge 0$:All electric currents are inward-positive. Each term $g(E-V)$ vanishes at its reversal potential $E$; $\mathrm{nS}\times \mathrm{mV}=\mathrm{pA}$. With constant parameters, the ordinary differential equation hasHere $G$ is total conductance, $1/G$ is effective electrical resistance, $V_{\infty }$ is the steady state and $\tau$ the time constant. Without imposed electric current, $V_{\infty }$ is a conductance-weighted average of the reversal potentials. This approximation omits spatial structure, changing ionic gradients and active voltage-gated ion channels; it calculates passive voltage responses, not actual action potential waveforms. See 3.1 Synapses for the mechanism behind the terms; the inward-positive convention here reverses that source's synaptic-current sign.

Take the same illustrative leak and capacitance as under shunting inhibition, start at $V(0)=-65\mathrm{mV}$ and set $I_{\mathrm{ext}}=0$. Opening $g_e=2\mathrm{nS}$ with $E_e=0\mathrm{mV}$ gives $V_{\infty }=-650/12\simeq -54.167\mathrm{mV}$ and $\tau \simeq 16.667\mathrm{ms}$. Its initial inward electric current is $2(0+65)=130\mathrm{pA}$. Adding $g_i=20\mathrm{nS}$ with $E_i=-65\mathrm{mV}$ changes $V_{\infty }$ to $(-650-1300)/32=-60.9375\mathrm{mV}$ and $\tau =6.25\mathrm{ms}$. This is shunting inhibition of the same excitatory drive.

For comparison, $g_i=20\mathrm{nS}$ with $E_i=-75\mathrm{mV}$ alone gives $V_{\infty }\simeq -71.667\mathrm{mV}$: hyperpolarization. With $E_i=-60\mathrm{mV}$ instead, it alone gives $V_{\infty }\simeq -61.667\mathrm{mV}$: depolarization. Yet adding this depolarizing conductance to the $g_e=2\mathrm{nS}$ excitatory drive lowers that drive's $V_{\infty }$ from $-54.167$ to $(-650-1200)/32=-57.8125\mathrm{mV}$. At an illustrative firing threshold $V=-50\mathrm{mV}$, its electric current is $20(-60+50)=-200\mathrm{pA}$, opposing threshold approach. The combined trace initially rises faster than the excitatory drive alone, before settling below it. Thus the sign of a voltage change at rest alone does not determine excitation or inhibition; a claim about firing must specify input strength, timing and the neuron's state.

Synaptic conductance describes how strongly activated synaptic ion channels conduct electric current for a given driving force. In the passive approximation, $I_{\mathrm{syn}}=g_{\mathrm{syn}}(E_{\mathrm{syn}}-V)$, with inward-positive electric current. It is the electrical conductance contribution of a synapse; its postsynaptic voltage response also depends on the driving force, the other membrane electrical conductances, and the capacitance. The synaptic potential model and shunting inhibition example show why a nonzero synaptic conductance can have zero electric current at rest.

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.

An inhibitory postsynaptic potential is a synaptic potential associated with decreased likelihood of a postsynaptic action potential. It can involve hyperpolarization or depolarization; an inhibitory conductance can even produce no measurable voltage change at rest. See synaptic potential and shunting inhibition for worked examples and sources.