Davatolhagh, M. F. | Search bioRxiv

bioRxiv2020

Striatal low-threshold spiking interneurons locally gate dopamine during learning

Low-threshold spiking interneurons (LTSIs) in the dorsomedial striatum are potent modulators of goal-directed learning. Here, we uncover a novel function for LTSIs in locally and directly gating striatal dopamine, using in vitro fast scan cyclic voltammetry as well as in vivo GRAB-DA sensor imaging and pharmacology during operant learning. We demonstrate that LTSIs, acting via GABAB signaling, attenuate dopamine release, thereby serving as local coordinators of striatal plasticity.

neuroscience↗

bioRxiv2020

Neurexin1α differentially regulates synaptic efficacy within striatal circuits

Mutations in genes essential for shared aspects of synaptic function throughout the CNS, such as the presynaptic adhesion molecule Neurexin1 (Nrxn1), are strongly implicated in neuropsychiatric pathophysiology. As the input nucleus of the basal ganglia, the striatum integrates diverse excitatory projections governing cognitive and motor control, and its functional impairment underlies neuropsychiatric disorders. While prior work has emphasized Neurexins contributions to synaptic transmission in hippocampus and brainstem, their function in striatal circuits remains unstudied. As Nrxn1 is highly expressed at striatal inputs, we employed optogenetic-mediated afferent recruitment of dorsal prefrontal cortex-dorsomedial striatal (DMS) connections, uncovering a decrease in net synaptic strength specifically onto indirect pathway spiny neurons in both Nrxn1+/- and Nrxn1-/- mice, driven by reductions in transmitter release probability. In contrast, thalamic excitatory inputs to DMS demonstrated relatively normal excitatory synaptic strength. These findings suggest that dysregulation of Nrxn1 modulates striatal function in an input and target-specific manner.

neuroscience↗