Presynaptic inhibition is an inhibitory input to a neuron to make it less likely to fire an action potential and communicate with downstream neurons. Inhibition can be provided both at the postsynapse and the presynapse. Presynaptic inhibition occurs when an inhibitory neurotransmitter, like GABA, acts on GABA receptors on the axon terminal. Presynaptic inhibition is ubiquitous among sensory neurons.
Function of presynaptic inhibition
neurons constantly provide information about the body's current state ; this constant influx of information is subject to modulation to enhance or diminish stimuli. Because there are unlimited stimuli at any given point to feel, it is imperative that these signals are appropriately filtered and compressed. To diminish certain stimuli, primary afferents receive inhibitory input to reduce their synaptic output. Impaired presynaptic inhibition has been implicated in many neurological disorders, such as chronic pain, epilepsy, autism, and fragile-X syndrome.
Mechanisms of presynaptic inhibition
The biophysical mechanism of presynaptic inhibition remains controversial. The presynaptic terminal has a distinct ionic composition that is high in chloride concentration which is largely due to cation-chloride cotransporters. Typically when GABA receptors are activated, it causes a chloride influx, which hyperpolarizes the cell. However, due to the high concentration of chloride at the presynaptic terminal and its altered reversal potential, GABA receptor activation actually causes a chloride efflux, and a resulting depolarization. This phenomenon is called primary afferent depolarization. Despite the depolarized potential, this still results in a reduction of neurotransmitter release and thus is still inhibition. There are three hypotheses which propose mechanisms behind this paradox:
The depolarized membrane causes inactivation of voltage-gated sodium channels on the terminals and therefore the action potential is prevented from propagating
Open GABA receptor channels act as a shunt, whereby current flows out of instead of concluding at the terminals
The depolarized membrane causes inactivation of voltage-gated calcium channels, preventing calcium influx at the synapse.
1933: Grasser & Graham observed depolarization that originated in the sensory axon terminals 1938: Baron & Matthews observed depolarization that originated in sensory axon terminals and the ventral root 1957: Frank & Fuortes coined the term "presynaptic inhibition" 1961: Eccles, Eccles, & Magni determined that the Dorsal Root Potential originated from depolarization in sensory axon terminals
