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Amygdala-Cortical Control of Striatal Plasticity Drives the Acquisition of Goal-Directed Action

Fisher, SD;Ferguson, LA;Bertran-Gonzalez, J;Balleine, BW;

In mammalian species, the capacity for goal-directed action relies on a process of cognitive-emotional integration, which melds the causal and incentive learning processes that link action-goal associations with the current value of the goal [1]. Recent evidence suggests that such integration depends on a cortical-limbic-striatal circuit centered on the posterior dorsomedial striatum (pDMS) [2]. Learning-related plasticity has been described at both classes of principal neuron in the pDMS, the direct (dSPNs) and indirect (iSPNs) pathway spiny projection neurons [3-5], and is thought to depend on inputs from prelimbic cortex (PL) [6] and the basolateral amygdala (BLA) [7]. Nevertheless, the relative contribution of these structures to the cellular changes associated with goal-directed learning has not been assessed, nor is it known whether any plasticity specific to the PL and BLA inputs to the pDMS is localized to dSPNs, iSPNs, or both cell types. Here, by combining instrumental conditioning with circuit-specific manipulations and ex vivo optogenetics in mice, we discovered that the PL and not the BLA input to pDMS is pivotal for goal-directed learning and that plasticity in the PL-pDMS pathway was bilateral and specific to dSPNs in the pDMS. Subsequent experiments revealed the BLA is critically but indirectly involved in striatal plasticity via its input to the PL; inactivation of the BLA projection to PL blocked goal-directed learning and prevented learning-related plasticity at dSPNs in pDMS.