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

• Published in: The Journal of physiology 2013-10, Vol.591 (19), p.4699-4710
• Main Authors: Kodangattil, Jayaraj N., Dacher, Matthieu, Authement, Michael E., Nugent, Fereshteh S.
• Format: Article
• Language: English
• Subjects: Animals; Dopamine; GABAergic Neurons - metabolism; GABAergic Neurons - physiology; Life Sciences; Long-Term Potentiation; Long-Term Synaptic Depression; Neurons and Cognition; Neuroscience: Cellular/Molecular; Parkinson's disease; Rats; Rats, Sprague-Dawley; Receptors, GABA-A - metabolism; Receptors, N-Methyl-D-Aspartate - metabolism; Rodents; Synapses - metabolism; Synapses - physiology; Synaptic Potentials; Ventral Tegmental Area - cytology; Ventral Tegmental Area - physiology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2013.257873

Key points •  GABAergic synapses onto ventral tegmental area (VTA) dopamine neurons express a bidirectional spike timing‐dependent plasticity (STDP; both long‐term potentiation and long‐term depression). •  GABAergic synapses in the VTA obey the classical Hebbian learning rules of STDP. •  GABAergic STDP in VTA dopamine neurons is expressed postsynaptically. •  GABAergic STDP is heterosynaptic and NMDA receptor dependent. •  Pairing of pre‐ and postsynaptic spiking is necessary for induction of GABAergic STDP.   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 an 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 long‐term potentiation (LTP) and long‐term depression (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 (NMDA receptor 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 behaviours. Moreover, this form of inhibitory plasticity may mediate some of the reinforcing, aversive and addictive properties of drugs of abuse.