IPSP

An inhibitory postsynaptic potential (IPSP) is a postsynaptic electrical change that decreases the likelihood that the neuron will fire an action potential. IPSPs typically hyperpolarize the postsynaptic membrane or increase its conductance, counteracting incoming excitatory signals.

Most IPSPs in the central nervous system are mediated by the neurotransmitters GABA (gamma-aminobutyric acid) and glycine. GABA operates mainly through ionotropic GABA_A and GABA_A-ρ receptors, and glycine receptors, which open chloride channels. Opening these channels drives the membrane potential toward the chloride reversal potential, usually resulting in hyperpolarization. Metabotropic GABA_B receptors activate potassium channels, producing slower, longer-lasting IPSPs. In developing neurons, intracellular chloride concentrations can be higher, sometimes making GABAergic responses depolarizing rather than inhibitory until maturation alters the chloride gradient.

IPSPs can also arise from shunting inhibition, where increased membrane conductance via open chloride or potassium channels reduces the impact of excitatory postsynaptic potentials without large changes in the resting potential.

Types of IPSPs include phasic inhibition, driven by brief, synaptic GABA release, and tonic inhibition, produced by ambient GABA acting on extrasynaptic receptors. IPSPs play a crucial role in shaping neural network activity by limiting excitation, controlling timing, and improving signal discrimination.

Dysfunction of inhibitory signaling is linked to neurological and psychiatric conditions, such as epilepsy and anxiety disorders. Pharmacologically, enhancing GABAergic inhibition with agonists or positive allosteric modulators (for example, benzodiazepines) is a common therapeutic strategy for reducing excessive neural excitability.