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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.

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.

For a negative neuronal membrane potential, depolarization raises it toward zero or beyond, making the interior less negative relative to the exterior. This describes a voltage change, not necessarily increased action potential generation; see the depolarizing inhibition example under synaptic potential.

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.

A neuron is a specialized biological cell that receives, integrates and transmits signals. Its shape separates places where inputs arrive from places where outputs reach other biological cells: this functional asymmetry is neuronal polarity. Understanding a neuron therefore means connecting its anatomy to changes in membrane potential, rather than treating it as a wire that merely forwards every input.

In a common multipolar neuron, branching dendrites receive inputs at synapses; the soma contains the cell nucleus and most major organelles; the axon carries signals to distant or nearby targets; and axon terminals form output contacts. All these regions belong to one biological cell enclosed by a continuous cell membrane. An axon can branch, allowing one neuron to influence several receiving biological cells.^[ref]

At an input chemical synapse, a neurotransmitter acts on a receptor, changing an electric current directly or through signal transduction.^[ref] A resulting synaptic potential contributes to synaptic integration in the dendrites and soma. In many spiking neurons, sufficiently strong depolarization recruits voltage-gated ion channels in the axon initial segment, initiating an action potential that propagates along the axon. At an output chemical synapse, calcium entry through voltage-gated ion channels promotes synaptic vesicle exocytosis, releasing neurotransmitter. An action potential is thus regenerated electrically along a cell membrane; it is not a packet of neurotransmitter travelling from the dendrites to the axon terminals.^[ref]

The compartments are specializations, not exclusive jobs. Inputs can contact the soma or axon as well as dendrites; dendrites can support active voltage-gated ion channels. Paired recordings from a pyramidal neuron's soma and dendrite or axon established that an action potential can begin in the axon and propagate back into the dendrites. The usual output direction therefore does not make every electrical signal strictly one-way.^[ref] An electrical synapse, which directly couples cytoplasms through gap junctions, also differs from the sending-and-receiving arrangement of a chemical synapse.^[ref]

Nor does every neuron have the upper diagram's shape. A bipolar neuron has two main processes, one dendrite and one axon; a multipolar neuron has several dendrites; and a pseudounipolar neuron has a single process from the soma that divides into peripheral and central branches. In the last arrangement, sensory signals can travel past the soma rather than obligatorily through it. These shape categories do not specify every neuron's receptor, connectivity or firing behavior.^[ref] Some neurons in the retina communicate through graded changes in membrane potential without generating action potentials.^[ref]

Why timing changes the computation. Synaptic integration can combine inputs at different locations, called spatial summation, and inputs arriving at different times, called temporal summation. A minimal example uses the leaky integrate-and-fire model with the illustrative parameters already given there: resting and reset membrane potential $-65\mathrm{mV}$, firing threshold $-50\mathrm{mV}$, electrical resistance $R=100\mathrm{M\Omega }$, capacitance $C=200\mathrm{pF}$, time constant $\tau =RC=20\mathrm{ms}$ and neuronal refractory period $2\mathrm{ms}$. These are chosen model values, not measured properties of a particular neuron. Before firing, a constant inward electric current $I$ starting from rest givesThe exponential function expresses the competition between charging the cell membrane's capacitance and leakage through its electrical resistance.^[ref]

Two $100\mathrm{pA}$ inputs, each lasting $40\mathrm{ms}$, produce different outputs depending on their timing. Either input alone reaches only $-56.3534\mathrm{mV}$. Applied together, they give $I=200\mathrm{pA}$ and reach threshold after $20\ln 4\mathrm{ms}\approx 27.7259\mathrm{ms}$, producing one action potential event during the pulse. If instead the second input begins $20\mathrm{ms}$ after the first ends, the earlier depolarization has partly decayed: the second pulse peaks at approximately $-55.9229\mathrm{mV}$ and neither pulse produces an action potential. The two-input protocols deliver the same total electric charge, $8\mathrm{pC}$, yet only the coincident protocol fires. Counting total input alone misses this timing dependence.

This example makes a neuron a detector of sufficiently clustered input, not a perfect logical gate: different parameters change the result. Actual dendrites introduce location-dependent filtering and active responses, and an inhibitory postsynaptic potential or shunting inhibition can change whether another input succeeds. The single-compartment leaky integrate-and-fire model omits these mechanisms.^[ref] Across connected neurons, branching axons distribute outputs while converging synapses combine inputs; spike trains can support temporal coding and rate coding, and synaptic plasticity changes the influence of an input. Connectivity and cellular dynamics together determine the computation.^[ref][ref]

Testing the connection between structure and function. Whole-cell recording connects anatomy to a measured membrane potential. In a published mouse protocol, a two-photon microscope guides solution-filled glass pipettes to neurons; an amplifier and bath reference electrode complete the electrical recording apparatus. A high-resistance seal forms against the cell membrane, then brief suction opens the membrane patch beneath the tip. In current clamp, the amplifier supplies a chosen electric current and records the resulting membrane potential, unlike voltage clamp, which controls voltage and measures electric current. The investigators used $500\mathrm{ms}$ current steps of several amplitudes to characterize excitability and firing, and negative current pulses to estimate input electrical resistance.^[ref]

The observable is a voltage trace, including graded responses and action potentials. Comparing injected electric current with that trace tests how input becomes output; it does not identify every underlying ion channel. The protocol checks access electrical resistance, which can distort voltage and action potential measurements, and includes intervals without stimulation to record spontaneous activity. In a teaching replication, repeated zero-input trials and monitoring baseline drift would provide further controls; these are recommended comparisons, not additional results attributed to the paper. A recording at the soma also cannot establish the local voltage everywhere in a branching dendrite, and this anesthetized preparation does not establish behavior in every awake neuron.^[ref]

A complementary experiment used simultaneous whole-cell recordings from the soma and an apical dendrite or axon of the same pyramidal neuron in a brain slice. The relative onset times of action potentials, together with sodium currents in excised dendrite membrane patches, supported axonal initiation followed by active propagation into dendrites. Pairing sites within one neuron is a useful comparison because it avoids confusing differences between cells with differences between compartments. Instrument timing and comparable recording quality would be essential controls when reproducing the inference. Only the published abstract was accessible here, so no unverified timing values, drug controls or channel distributions are supplied.^[ref]

A passive dendritic cable models a uniform dendrite with axial electrical resistance, membrane leak and membrane capacitance, excluding active ion channels. Let $r_a$ be axial electrical resistance per length, $r_m$ membrane electrical resistance times length, and $c_m$ membrane capacitance per length. For voltage deviation $v=V-E_L$ from the leak reversal potential, electric charge conservation gives the partial differential equation$i$ is imposed inward electric current per length. Units are $r_a:\Omega /\mathrm{m}$, $r_m:\Omega \mathrm{m}$ and $c_m:\mathrm{F}/\mathrm{m}$, so ${\tau }_m$ is a time and $\lambda$ a length. On a source-free semi-infinite cable with imposed $v(0)=v_0$ and $v(x)\to 0$ as $x\to \infty$, the steady state isDifferentiate twice to verify the ordinary differential equation ${\lambda }^2{v}^{\prime \prime }-v=0$. At $x=\lambda$, the amplitude is $e^{-1}\approx 0.368$ of the boundary amplitude. This is a stationary attenuation law, not the complete waveform of a brief EPSP. Transient passive spread also broadens and delays responses. Finite ends, branch points and the soma's load alter the solution; distance alone cannot specify every real synaptic potential.^[ref]

The spatial panel uses two compartments with membrane potentials $V_s,V_d$, one representing the soma and one a dendrite. Set $v_s=V_s-E_L$, $v_d=V_d-E_L$, with leak reversal potential $E_L=-65\mathrm{mV}$, each membrane capacitance $C=100\mathrm{pF}$, each leak electrical conductance $g_L=5\mathrm{nS}$ and axial electrical conductance $g_c=10\mathrm{nS}$. Electric charge conservation givesThis chosen passive model has two decay time constants, $C/g_L=20\mathrm{ms}$ for the equal-voltage mode and $C/(g_L+2g_c)=4\mathrm{ms}$ for the voltage-difference mode. Starting from rest, a $100\mathrm{pA}$ step into the soma gives, with $u$ the time since onset,while the same step into the dendrite gives$u$ is expressed in $\mathrm{ms}$. Their long-time rises are $12$ and $8\mathrm{mV}$ respectively. Applying both inputs gives $20(1-e^{-u/20})\mathrm{mV}$ exactly: spatial attenuation coexists with linear summation of prescribed electric currents. After the steps end, both modes decay with their respective time constants. This deliberately coarse model is not a reconstructed dendrite or a fit to the experiment above.

The conductance panels use the existing one-compartment synaptic potential equation, with $C=200\mathrm{pF}$, $g_L=10\mathrm{nS}$, $E_L=-65\mathrm{mV}$ and excitatory reversal potential $E_e=0\mathrm{mV}$. For a constant excitatory synaptic conductance $g_e$, the steady state voltage rise and membrane time constant areEach isolated $2\mathrm{nS}$ input has a limiting rise $130/12\approx 10.833\mathrm{mV}$. Adding those isolated rises predicts $21.667\mathrm{mV}$, but opening both together gives $260/14\approx 18.571\mathrm{mV}$. The two conductances share a changing driving force. This is sublinear input summation even though the voltage ordinary differential equation is linear for each prescribed conductance waveform.

Add $g_i=20\mathrm{nS}$ with reversal potential $E_i=E_L$ to the joint $4\mathrm{nS}$ excitation. The limiting rise becomes $260/34\approx 7.647\mathrm{mV}$ and the membrane time constant becomes $200/34\approx 5.882\mathrm{ms}$. The shunt alone leaves rest unchanged. At the joint-excitation-only steady state $V\approx -46.429\mathrm{mV}$, however, its inward electric current would be $20(-65+46.429)\approx -371.429\mathrm{pA}$: it opposes that excursion. The finite $50\mathrm{ms}$ traces in the diagram approach, but need not reach, these limiting voltages. See shunting inhibition for the constant-electric current comparison.

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.

Spatial summation combines inputs arriving at different synapses. Location matters because a dendrite has axial electrical resistance and leaky membrane capacitance: a local synaptic potential need not arrive at the soma with its original amplitude or time course. A passive dendritic cable makes this attenuation explicit. The superposition principle applies to fixed electric current inputs in a linear passive model, but adding synaptic conductances changes the model's coefficients. Compare voltage changes relative to the same baseline, rather than adding absolute membrane potentials.

A motivating experiment. A 2004 study used $300$–$350\mu \mathrm{m}$ cortical slices from $18$–$28$-day-old rats at $35$–$36{}^{\circ }\mathrm{C}$. Somatic whole-cell recordings measured EPSPs in layer-5 pyramidal neurons. Two fine stimulating electrodes were positioned beside imaged dendrites; calcium-sensitive dye localized activation. Each site was stimulated alone, then both together, usually with paired pulses $20\mathrm{ms}$ apart. Comparing the combined voltage trace with the sum of individual changes tested the summation rule. Nearby inputs on one branch showed strong amplification at intermediate strengths; inputs on different branches were approximately linear.^[ref]

Blocking both excitatory receptor classes eliminated voltage and calcium responses, checking against direct electrical activation. NMDA receptor blockers eliminated or markedly reduced amplification; comparisons with inhibition intact and blocked addressed inhibitory contributions. These controls support local active integration. Passing axons could still recruit unintended synapses; somatic voltage does not measure every local membrane potential. The study tested subthreshold slice responses and pairs of branches, not arbitrary activity in an intact brain.^[ref]

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.

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.

Synaptic integration is the conversion of inputs at a neuron's synapses into a changing membrane potential and, in a spiking neuron, the timing or absence of action potentials. Spatial summation concerns inputs at different locations; temporal summation concerns inputs at different times. A useful question is whether individually ineffective inputs can act together, and whether an inhibitory postsynaptic potential changes that cooperation. The answer depends on location, timing and the receiving neuron's state.

A synaptic potential is a voltage response, whereas synaptic conductance describes activated ion channels. With inward-positive electric current, the contribution of input $j$ isHere $g_j$ is its synaptic conductance, $E_j$ its reversal potential and $V$ the local membrane potential. The driving force $E_j-V$ is an electric potential difference. An EPSP generally brings the membrane potential toward a more positive reversal potential, but its driving force shrinks during depolarization. An IPSP need not produce hyperpolarization: a reversal potential above rest but below the neuronal firing threshold can produce depolarization while opposing a larger excursion. At $E_j=V$, the added synaptic conductance initially carries zero electric current yet can cause shunting inhibition of another input.^[ref]

Two distinct nonlinearities matter. Even a passive cell membrane can show sublinear synaptic integration when added synaptic conductances reduce driving force and effective electrical resistance. Active voltage-gated ion channels and NMDA receptors can instead amplify sufficiently concentrated inputs and produce a dendritic spike. Neither summing prescribed electric currents nor adding separate measured EPSPs is an exact universal rule for a branching neuron.^[ref]

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.