Dopamine Receptor Activation Is Required for GABAergic Spike Timing-Dependent Plasticity in Response to Complex Spike...

One of the most influential synaptic learning rules explored in the past decades is activity dependent spike-timing-dependent plasticity (STDP). In STDP, synapses are either potentiated or depressed based on the order of pre- and postsynaptic neuronal activation within narrow, milliseconds-long, time intervals. STDP is subject to neuromodulation by dopamine (DA), a potent neurotransmitter that significantly impacts synaptic plasticity and reward-related behavioral learning. Previously, we demonstrated that GABAergic synapses onto ventral tegmental area (VTA) DA neurons are able to express STDP (Kodangattil et al., 2013), however it is still unclear whether DA modulates inhibitory STDP in the VTA. Here, we used whole-cell recordings in rat midbrain slices to investigate whether DA D1-like and/or D2-like receptor (D1R/D2R) activation is required for induction of STDP in response to a complex pattern of spiking. We found that VTA but not Substantia nigra pars compact (SNc) DA neurons exhibit long-term depression (LTD_GABA) in response to a combination of positive (pre-post) and negative (post-pre) timing of spiking (a complex STDP protocol). Blockade of either D1Rs or D2Rs prevented the induction of LTD_GABA while activation of D1Rs did not affect the plasticity in response to this complex STDP protocol in VTA DA neurons.Our data suggest that this DA-dependent GABAergic STDP is selectively expressed at GABAergic synapses onto VTA DA neurons which could be targeted by drugs of abuse to mediate drug-induced modulation of DA signaling within the VTA, as well as in VTA-projection areas, thereby affecting reward-related learning and drug-associated memories.