Claustrum serotonin and spike-timing plasticity associated with cognitive deficits after cocaine

The project will test the hypothesis that cocaine changes the timing window for induction of long-term synaptic plasticity in CLA-ACC neurons, resulting in cognitive flexibility deficits and increased drug seeking behavior. It will also test the hypothesis that a single activation of 5HT2ARs in the CLA reverses cocaine-induced LTD, leading to a long-term improvement of cognitive flexibility and attenuated reinstatement of cocaine-seeking behavior. This will be achieved through targeted microinjections of DOI into the CLA of rats trained to self-administer cocaine, using patch-clamp electrophysiology to establish the timing rules for serotonergic modulation of spike-timing dependent plasticity of excitatory synapses onto CLA-ACC neurons of cocaine exposed rats, and combining chemogenetics with Ca2+ imaging in ACC-containing brain slices to establish the extent to which CLA neurons control ACC excitability in control and cocaine experienced rats.