Excitatory Postsynaptic PotentialEdit
An excitatory postsynaptic potential (EPSP) is a depolarizing change in the membrane potential of a postsynaptic neuron that makes the cell more likely to fire an action potential. In the central nervous system, EPSPs arise when an excitatory synapse releases neurotransmitter, most often glutamate, onto the dendrites or soma of a postsynaptic cell. The depolarization is typically mediated primarily by AMPA-type receptors, with NMDA receptors contributing under particular conditions. An EPSP is a graded, transient event: its amplitude depends on the amount of transmitter released, the number of receptors activated, and the electrical properties of the postsynaptic cell, and it decays as the membrane repolarizes and the local conductances return to baseline. Because EPSPs are subthreshold, their cumulative effect—through spatial and temporal summation—determines whether the neuron reaches the threshold to generate an action potential at the axon hillock. neuron synapse glutamate AMPA receptor NMDA receptor postsynaptic potential action potential
Mechanism of generation
EPSPs are produced when neurotransmitter activates cation-permeable receptors on the postsynaptic membrane. The archetype is the AMPA receptor, a ligand-gated ion channel that conducts Na+ inward and K+ outward, resulting in a net inward current and membrane depolarization. Some AMPA receptors are permeable to Ca2+ as well, which can influence intracellular signaling pathways. NMDA receptors, another class of glutamate-gated channels, also contribute to EPSPs but have distinct properties: they are permeable to Na+, K+, and Ca2+, and their channel opening requires depolarization to relieve a Mg2+ block. This voltage dependence gives NMDA receptors a role in coincidence detection and longer-lasting depolarizations. The combined activity of these receptor types shapes the rise, peak, and duration of an EPSP, which typically occurs on a millisecond-to-tens-of-milliseconds timescale but can be extended in certain dendritic compartments. AMPA receptor NMDA receptor glutamate excitatory synapse dendrite
The postsynaptic response also depends on the passive electrical properties of the neuron, including membrane resistance and capacitance, as well as the geometry of the dendritic tree. Distal synapses must propagate the EPSP through dendritic cables to influence the axon hillock, where the decision to fire is made. This propagation, or electrotonic filtering, causes EPSPs to attenuate with distance and time, producing a graded signal that is integration-dependent rather than a fixed all-or-none event. dendrite membrane potential cable theory axon hillock
Temporal and spatial summation
Because neurons receive thousands of synaptic inputs, EPSPs are rarely acting in isolation. Temporal summation occurs when successive EPSPs arrive before the membrane has returned to baseline, summing their depolarizations to bring the neuron closer to firing. Spatial summation arises from EPSPs generated at multiple synaptic sites simultaneously; their local inputs combine to shape the overall postsynaptic response. The extent of summation is influenced by the time constant of the membrane and by inhibitory inputs that produce hyperpolarizing or shunting effects. The interplay of excitatory and inhibitory signals shapes the precise pattern of neuronal output in circuits involved in perception, movement, and cognition. synapse neural coding inhibitory postsynaptic potential shunting inhibition
EPSPs are most effective when they converge near the soma or at the axon initial segment, where the influence on action-potential generation is greatest. In dendrites, local nonlinear events, such as dendritic spikes mediated by NMDA receptors or voltage-gated channels, can amplify or modify distal EPSPs, adding complexity to how inputs are integrated. axon initial segment dendritic spike neural integration
Role in synaptic integration and plasticity
EPSPs are foundational to how neural circuits perform information processing. The timing and location of excitatory inputs determine how strongly a neuron responds to a given stimulus, contributing to feature detection, pattern recognition, and motor planning. EPSPs also participate in activity-dependent synaptic plasticity. Repeated coincident activity that produces sufficient Ca2+ influx through NMDA receptors can trigger signaling cascades that underlie long-term potentiation (LTP) or long-term depression (LTD), strengthening or weakening synapses and reshaping network connectivity. synaptic plasticity long-term potentiation long-term depression coincidence detection
Neuromodulatory systems—such as those releasing dopamine or acetylcholine—can alter EPSP strength and duration by changing receptor properties, membrane conductances, or the excitability of the postsynaptic cell. These modulators can bias network states toward particular computational modes (for example, heightened attention or learning readiness) by shifting how EPSPs influence spike generation. dopamine acetylcholine neuromodulation
Experimental perspective and debates
Modern study of EPSPs relies on techniques like patch-clamp recording, two-photon imaging, and pharmacological dissection of receptor subtypes. Researchers commonly use receptor antagonists to isolate contributions of AMPA and NMDA receptors (for example, CNQX blocks AMPA receptors, while APV blocks NMDA receptors). Debates in the field concern, for instance, the relative importance of NMDA receptor–mediated currents in fast, in vivo synaptic integration versus their role in slower, plasticity-related processes. Another area of discussion centers on how dendritic geometry and active conductances shape the effective summation of EPSPs, particularly in cortical and hippocampal circuits where local dendritic spikes can profoundly influence somatic output. CNQX APV two-photon microscopy patch-clamp circuit dynamics
Clinical and computational relevance
Abnormal EPSP dynamics can contribute to neurological dysfunction. Excessive excitatory drive or impaired inhibitory control can predispose to hyperexcitability and seizures. NMDA receptor dysfunction has been implicated in various neuropsychiatric and neurodevelopmental conditions, including schizophrenia models that emphasize disrupted glutamatergic signaling. Conversely, strategies that dampen excessive EPSP activity or prevent excitotoxic Ca2+ influx are explored in stroke and neurodegenerative contexts. These concerns underscore the importance of EPSP dynamics for both healthy brain function and disease. epilepsy excitotoxicity schizophrenia stroke