Description:

The Department of Physiology welcomes Dr. Shana Augustin with NIH.

Striatal neuromodulators have critical roles in motor control, decision-making and addiction. These neuromodulators exert their functions through G-protein-coupled receptors (GPCRs) on striatal neurons that activate second messenger intracellular cascades to affect neuronal signaling. Thus, understanding the cellular, subcellular, and synaptic mechanisms underlying neuromodulation is critical to advancing our knowledge of striatal function. I have taken a multifaceted approach to study striatal neuromodulation. The focus of my recent research has been the action of dopamine on different cellular populations of striatal dopamine D2 receptors in the induction of endocannabinoid (eCB)-dependent long-term depression (LTD), the downstream activation/inhibition of the cAMP-PKA signaling pathway, as well as the behavioral implications of this signaling. I identified a dual mechanism for D2R modulation of corticostriatal LTD induction at medium spiny neuron (MSN) synapses involving D2Rs on cholinergic interneurons and indirect pathway MSNs. In addition, I can simultaneously measure dopamine release and subsequent downstream GPCR mediated cAMP-PKA signaling in striatal brain slices using a genetically encoded fluorescent (GEF) cAMP sensor, cAMP Difference Detector in situ (cADDis), and Fast-Scan Cyclic Voltammetry. These experiments indicate that during afferent stimulation MSN-cAMP signaling is primarily influenced by dopamine transmission. Additionally, I have shown that D2 MSN-cAMP signaling is important for action initiation. Drugs of abuse can interfere with eCB-mediated synaptic plasticity in a synapse-specific, and possibly in an eCB type selective manner. I am using a GEF sensor that enables the optical recording of eCBs in real-time and in behaving animals, as well as eCB-specific conditional knockout animals to understand how the eCB system influences synapses and circuits to promote the pathophysiology of Alcohol Use Disorder. Using a multidisciplinary approach, these experiments have helped to further elucidate unique functions of GPCR neuromodulation within the basal ganglia circuitry and the functional relevance of these circuits.