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

Area of Science:

• Neuroscience
• Synaptic Plasticity
• Addiction Research

Background:

• Persistent changes in synaptic strength in ventral tegmental area (VTA) dopamine (DA) neurons are implicated in the transition to compulsive drug use.
• While glutamatergic plasticity in the VTA is well-studied, the rules governing GABAergic plasticity remain largely unknown.
• Spike-timing-dependent plasticity (STDP) is a key mechanism for information processing and storage, with emerging evidence at inhibitory synapses.

Purpose of the Study:

• To investigate whether near-coincident pre- and postsynaptic firing induces lasting changes in synaptic efficacy at VTA GABAergic synapses.
• To determine the underlying mechanisms and properties of STDP at inhibitory synapses in the VTA.

Main Methods:

• Whole-cell recordings were performed in rat midbrain slices.
• Stimulation protocols were designed to induce and measure spike-timing-dependent plasticity (STDP) at GABAergic synapses onto VTA DA neurons.

Main Results:

• A Hebbian form of STDP, including long-term potentiation (LTP) and long-term depression (LTD), was successfully induced at GABAergic synapses onto VTA DA neurons.
• This GABAergic STDP relies on the precise temporal order of pre- and postsynaptic spiking.
• GABAergic STDP was found to be heterosynaptic, NMDA receptor-dependent, and triggered by correlated activity between presynaptic glutamatergic input and postsynaptic DA cells.
• The plasticity was postsynaptic and associative, requiring both pre- and postsynaptic spiking.

Conclusions:

• STDP at GABAergic synapses in the VTA provides a physiologically relevant form of inhibitory plasticity.
• This plasticity may contribute to the natural reinforcement of reward-related behaviors.
• GABAergic STDP in the VTA could mediate some of the reinforcing, aversive, and addictive properties of drugs of abuse.