Thirtamara Rajamani, K. | bioRxiv Science

bioRxiv2023

Altered neural activity in the mesoaccumbens pathway underlies impaired social reward processing in Shank3-deficient rats

Social behaviors are crucial for human connection and belonging, often impacted in conditions like Autism Spectrum Disorder (ASD). The mesoaccumbens pathway (VTA and NAc) plays a pivotal role in social behavior and is implicated in ASD. However, the impact of ASD-related mutations on social reward processing remains insufficiently explored. This study focuses on the Shank3 mutation, associated with a rare genetic condition and linked to ASD, examining its influence on the mesoaccumbens pathway during behavior, using the Shank3-deficient rat model. Our findings indicate that Shank3-deficient rats exhibit atypical social interactions and have difficulty adjusting behavior based on reward values, associated with modified neuronal activity of VTA dopaminergic and GABAergic neurons and reduced dopamine release in the NAc. Moreover, we demonstrate that manipulating VTA neuronal activity can normalize this behavior, providing insights into the effects of Shank3 mutations on social reward and behavior, and identify a potential neural pathway for intervention.

neuroscience↗

bioRxiv2022

Oxytocin activity in the Paraventricular and Supramammillary Nuclei of the Hypothalamus is Essential for Social Recognition Memory in Rats

Oxytocin plays an important role in modulating social recognition memory. However, the direct implication of oxytocin neurons of the paraventricular nucleus of the hypothalamus (PVH) and their downstream hypothalamic targets in regulating short- and long-term forms of social recognition memory has not been fully investigated. In this study, we employed a chemogenetic approach to target the activity of PVH oxytocin neurons in male rats and found that specific silencing of this neuronal population led to an impairment in short- and long-term social recognition memory. We combined viral mediated fluorescent labeling of oxytocin neurons with immunohistochemical techniques and identified the supramammillary nucleus (SuM) of the hypothalamus as a target of PVH oxytocinergic axonal projections in rats. We used multiplex fluorescence in-situ hybridization to label oxytocin receptors in the SuM and determined that they are predominantly expressed in glutamatergic neurons, including those that project to the CA2 region of the hippocampus. Finally, we used a highly selective oxytocin receptor antagonist in the SuM to examine the involvement of oxytocin signaling in modulating short- and long-term social recognition memory and found that it is necessary for the formation of both. This study discovered a previously undescribed role for the SuM in regulating social recognition memory via oxytocin signaling and reinforced the specific role of PVH oxytocin neurons in regulating this form of memory.

neuroscience↗