Sunday, October 1, 2023
10/1/2023
PROJECT SUMMARY I propose to study the role of dopamine signaling within the neostriatum in the context of auditory-based decision- making. Decision-making based on sensory perception is an integral part of everyday life and a cornerstone of ones ability to respond to the environment with appropriate actions. This pivotal process is dysfunctional in neuropsychiatric disorders such as Parkinson’s disease and schizophrenia. Studies demonstrate that the neostriatum is a neural correlate for perception-based decision-making and that striatal neurotransmitter imbalances can disrupt such behaviors. Our lab studies a caudal portion of the dorsal striatum—referred to as the “auditory striatum,” and we have shown that this striatal region is important for auditory cue-based decision- making and reinforcement learning. While it has been shown that auditory corticostriatal projections drive auditory decision-making in rodents, it is unclear how established striatal neuromodulators including dopamine influence these functions. Recent evidence indicates that neuromodulatory control and behavioral states play a critical role in a wide variety of auditory behaviors. My preliminary pharmacological and tract-tracing data indicate that dopamine, a key striatal neuromodulator, indeed plays a role in within the auditory striatum for auditory decision-making. These data and previous literature contribute to my central hypothesis, which is that dopaminergic signaling in the auditory striatum contributes to auditory decision-making by modulating striatal sound representation. To address this hypothesis and to hone in on dopamine’s role, I propose two aims. First, in Aim 1, I will monitor the activity of identified auditory striatum-projecting dopaminergic substantia nigra pars compacta neurons through in vivo Ca2+ imaging and map these dynamics with respect to specific epochs of the auditory decision-making task. Knowledge of how the activity of these dopamine neurons changes with respect to decision-making behavior will allow me to infer how dopaminergic mechanisms modulate choice accuracy. For instance, if DA activity corresponds to sound cue presentation, it may suggest that DA activity modulates sound representation in the auditory striatum. In Aim 2, I will evaluate the importance of dopaminergic modulation in the auditory task by optogenetically inhibiting dopaminergic projections during the same sets of defined epochs of the auditory decision-making task evaluated in Aim 1. This will demonstrate whether dopamine is necessary for mediating specific aspects of auditory decision-making, including sound cue representation. Overall, I will use circuit-specific labeling, microendoscopic monitoring, and optogenetics in mice to investigate the role of dopamine in auditory decision-making. Results from this study will advance understanding of how striatal dopamine contributes to auditory perceptual decision-making, which in turn could bring new etiological insights for auditory processing disorders and neuropsychiatric disease.
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