Friday, April 26, 2024
4/26/2024
The proposed studies will uncover components of a core neural system that underlies affiliative, rewarding, non-sexual social communication. In cases of depression, anxiety, and autism spectrum disorders, social interactions that are typically rewarding can become aversive. Deficits can also be context specific. For example, some autistic individuals can make directed requests (e.g., for food) that can be extrinsically reinforced (e.g., by receipt of food) but exhibit profound deficits in affiliative communication (e.g., nonsexual, chitchat) that promotes social bonds and is rewarding but does not result in an immediate, obvious extrinsic reinforcer. Many studies focus on mechanisms underlying goal-directed, extrinsically rewarded behaviors (e.g., food-, mate-, or drug-directed); however, these mechanisms appear to differ from those underlying intrinsically rewarded, affiliative social behaviors, leaving a critical gap in basic knowledge about mechanisms underlying non-sexual, affiliative communication. Studies taking advantage of the unique communication properties of songbirds reveal an important role for mu opioid receptors (MORs) in the mPOA in both facilitating and rewarding a form of non-sexual, affiliative singing behavior; whereas D1 dopamine receptors (D1Rs) in mPOA may play a role in social motivation. MORs and D1Rs colocalize within the mPOA, and parallel lines of research demonstrate critical roles for MORs and D1Rs in the mPOA in male sexual motivation (i.e., D1Rs) and sexual reward (i.e., MORs), yet almost no studies have explored interactions between the two, and the role of intra-mPOA MOR-D1R interactions and key output pathways in non-sexual affiliative communication, social motivation, and reward is unknown. The central hypothesis is that MORs and D1Rs in mPOA and opioid- and dopamine-sensitive projections from mPOA to VTA and mPOA to PAG underlie affiliative song and play distinct roles in social motivation and reward. The rationale is the need for basic information on core social circuits that underlie behaviors disrupted by mental illness. Three specific aims are proposed: In Aim 1, shRNA will be used to knockdown MORs or D1Rs in mPOA to determine their selective contributions to affiliative song, social motivation, and social reward. In Aim 2, effects of the same manipulations on the ability of pharmacological MOR and D1R stimulation to facilitate affiliative song, motivation, and reward will be tested to determine the role of MOR-D1R interactions. In Aim 3, effects of chemogenetic activation and inactivation of projections from mPOA to VTA and mPOA to PAG on song, social motivation, and reward will be examined, followed by labeling for immediate early genes, MORs and D1Rs to determine the degree to which MOR and D1R colocalize to active projections. The approach is innovative because it advances the understanding of intrinsically rewarded social behavior with the goal of identifying fundamental, conserved mechanisms. The proposal is significant because it will elucidate the role of MOR-D1R interactions in non-sexual, affiliative social behaviors and provide insight into core neural circuits that may be disrupted by mental illness in humans.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
