Evaluating the function and activity dynamics of thalamic inputs for reward seeking and consumption

Univ Of North Carolina Chapel Hill, Chapel Hill NC

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Abstract

? DESCRIPTION (provided by applicant): Function and natural activity dynamics of thalamic inputs for reward seeking. Compulsive reward seeking and taking are hallmarks of addiction, although the precise neural circuits that orchestrate these basic motivational states remain unclear. This is in part due to a lack of experimental feasibility, as it has been difficult to conrol and monitor the activity of cell-type specific neurons in vivo. For example, the paraventricular thalamus (PVT) is a midline thalamic nucleus that interfaces with motivational circuits, is a critical regulator of feeding, and is necessary for reinstatement in several models of drug seeking. Despite this, how PVT neurons function within a broader circuit to regulate these motivational states is unknown. Thus, the objective of this project is to use contemporary tools to study the precise neurocircuitry that engages PVT for the control of reward seeking. Here I propose to identify the function and natural activity dynamics of two primary PVT inputs, particularly from the lateral hypothalamus (LH) and prelimbic cortex (PLc), for the control of reward seeking. The function of PVT inputs for reward seeking will be evaluated with inhibitory optogenetics during distinct phases of a cue-induced reward-seeking task (Aim 1). Furthermore, the natural activity dynamics of these projection-specific neurons will be visualized during reward seeking and taking through deep-brain calcium imaging in awake, freely moving mice (Aim 2). Based on my preliminary data and published work by my sponsor and others, I hypothesize that PVT-projecting LH neurons will be active and necessary for reward seeking and consumption. In contrast, based on my preliminary data and my previously published work, I hypothesize that PVT-projecting PLc neurons will be active and necessary specifically for cue-driven reward seeking, but not reward seeking and consumption in general. These data would suggest that the PVT acts to integrate distinct signals regarding motivational drive (LH) and environmental stimuli (PLc) to regulate reward-seeking behavior. Regardless of the results, these experiments will identify the function and natural activity dynamics of LH-PVT and PLc-PVT neurons for the control of reward seeking and taking.