TrkB-dependent disinhibition of the nucleus accumbens is enhanced by ethanol.

The nucleus accumbens is a critical integration center for reward-related circuitry and is comprised primarily of medium spiny projection neurons. The dynamic balance of excitation and inhibition onto medium spiny neurons determines the output of this structure. While nucleus accumbens excitatory synaptic plasticity is well-characterized, inhibitory synaptic plasticity mechanisms and their potential relevance to shaping motivated behaviors is poorly understood. Here we report the discovery of long-term depression of inhibitory synaptic transmission in the mouse nucleus accumbens core. This long-term depression is postsynaptically expressed, tropomyosin kinase B (TrkB) receptor-mediated, and augmented in the presence of ethanol. Our findings support the emerging view that TrkB signaling regulates inhibitory synaptic plasticity and suggest this mechanism in the nucleus accumbens as a target for ethanol modulation of reward.