Presynaptic regulation of dopamine release in corpus striatum monitored in vitro in real time by fast cyclic voltammetry

Along with development and application of Opto-D1R, enabling causal identification of postsynaptic NAc D1 MSNs regulating social behavior, these results demonstrate integrative value of complementary optical techniques in causally mapping specific projections and postsynaptic targets within neural circuitry. Our observation that VTA DA neuron activity is causally involved in bidirectional modulation of same-sex social interaction supports prior pharmacological studies implicating DA in affiliative behaviors (Aragona et al., 2006; Curtis and Wang, 2005; Gingrich et al., 2000; Liu and Wang, 2003), though it had been previously difficult to determine the precise site and mechanism of action of DA as receptors are expressed postsynaptically as well as presynaptically on VTA terminals (Benoit-Marand et al., 2001; Palij et al., 1990), and pharmacological agents could exert behavioral effects either by enhancing DA signaling downstream or by dampening VTA activity via inhibitory autoreceptors. Additionally, NAc-projecting VTA neurons may co-release other neurotransmitters such as glutamate (Stuber et al., 2010), and DA pharmacological manipulations do not typically capture this synergy present in endogenous VTA activity.