Prefrontal cortical mechanisms for arousal modulation and alcohol drinking

Neuromodulation associated with autonomic arousal can fundamentally shift information processing in the brain, imbuing state-dependence to neuronal processes underlying perception, action, and cognition. Given these widespread effects, it is unsurprising that dysregulation of arousal is associated with numerous neuropsychiatric conditions, including alcohol use disorder. A major goal of our work is to dissect how prefrontal cortical circuits exert top-down control over arousal. Our work combines cutting-edge experimental approaches with sophisticated behavioral paradigms in mice to reveal the microcircuit and long-range circuit principles that coordinate reciprocal interactions between autonomic arousal and alcohol drinking. We are also interested in determining how ACC modulation of arousal contributes to brain-wide information processing and how ACC-dependent aberrant arousal contributes to other neuropsychiatric conditions like chronic pain.

Contributing lab members: Nithik Chintalacheruvu, Esther Ko, Anagha Kalelkar

Astrocyte-neuron interactions in the striatum contributing to movement in health and Parkinson’s disease

Striatum, the main input nucleus of the basal ganglia, sits at the critical nexus of a brain-wide circuitry that produces movement. Dopaminergic neuromodulation from the midbrain plays a key role in coordinating movement-related striatal activity. Indeed, degeneration of dopamine producing neurons in Parkinson’s disease (PD) and the resulting loss of dopamine disrupts synaptic transmission in striatal projection neurons, leading to aberrant network activity that causes deficits in coordinated motor control. Astrocytes are non-neuronal glia cells that are well poised to coordinate network activity of striatal neurons. Current therapies to treat the motor symptoms of Parkinson’s disease (PD) predominantly supplement lost dopaminergic neuromodulation to mitigate striatal projection neuron dysfunction. A complementary strategy is to directly target endogenous neuromodulation through the striatum’s astrocyte network. We are testing how astrocyte calcium signaling contributes to movement-related activity of specific striatal neurons and how dysregulation of this process with dopamine loss contributes to the movement symptoms of PD.

Contributing lab members: Wesley Evans, Sanya Ravoori, Abhishek Nayak