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Spike timing‐dependent plasticity at GABAergic synapses in the Ventral tegmental area

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The Journal of Physiology

Published online on

Abstract

Abstract  Persistent changes in excitatory and inhibitory synaptic strengths to the ventral tegmental area (VTA) dopamine (DA) neurons in response to addictive drugs may underlie the transition from casual to compulsive drug use. While enormous amount of work has been done in the area of glutamatergic plasticity of the VTA, little is known regarding the learning rules governing GABAergic plasticity in the VTA. Spike‐timing‐dependent plasticity, STDP, has attracted considerable attention primarily due to its potential roles in processing and storage of information in the brain and there is emerging evidence for the existence of STDP at inhibitory synapses. We therefore used whole‐cell recordings in rat midbrain slices to investigate whether near coincident pre‐ and postsynaptic firing induces a lasting change in synaptic efficacy of VTA GABAergic synapses. We found that a Hebbian form of STDP including LTP and LTD can be induced at GABAergic synapses onto VTA DA neurons and relies on the precise temporal order of pre‐and postsynaptic spiking. Importantly, GABAergic STDP is heterosynaptic (NMDR‐dependent): triggered by correlated activities of the presynaptic glutamatergic input and postsynaptic DA cells. GABAergic STDP is postsynaptic and has an associative component since pre‐ or postsynaptic spiking per se did not induce STDP. STDP of GABAergic synapses in the VTA provides physiologically relevant forms of inhibitory plasticity that may underlie natural reinforcement of reward‐related behaviors. Moreover, this form of inhibitory plasticity may mediate some of the reinforcing, aversive and addictive properties of drugs of abuse. This article is protected by copyright. All rights reserved