Oxytocin signaling in the ventral hippocampus: from modulation of the local circuit to socio-sexual behavior

• Applicant: Professor Dr. Valery Grinevich
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: from 2019 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 433153533

The hypothalamic neuropeptide oxytocin (OT) modulates a plethora of socio-sexual behaviors. Due to the fact that social cognition and relationship rely on the general ability of a subject to reconstruct and relate memory representations, in this project we focused on the ventral hippocampus (vHippo), which has been recently reported as a controlling social memory hub. Intriguingly, the experimental inhibition of CA1 region of vHippo leads to disturbance of social behavior, similar to that observed in animal models lacking OT or its receptor (OTR). Therefore, we propose that social function of the vHippo is related to OT action. Although the vHippo CA1 region receives direct OT-ergic input, neuronal types underlying OT-mediated modulation of neuronal ensembles in this structure, and their functional contribution to the social behavior remains unknown. In our preliminary experiments, implementing newly generated OTR-Cre knock-in rats and viral vectors, we identified two populations of OTR+ neurons in the vHippo: parvalbumin-positive interneurons and principal cells (PCs), which reside outside the CA1 principal cell layer. Application of OTR agonist to acute vHippo slices resulted in co-activation of both OTR+ interneurons and OTR+ PCs, while OTR- PCs were silent. Further, our viral-vector based tracing studies revealed that OTR+ PCs specifically project to granule cell layer of the accessory olfactory bulb (AOB) – the hub structure of sexual (pheromonal) information processing. Knowing that OTR+ PCs target the AOB, we propose that the vHippo may tune perception of sexually valid olfactory information via selectively strengthening the connection between OTR+ PCs in the vHippo and extrinsic component of the network – the AOB. Following this hypothesis, we will perform detailed electrophysiological and anatomical analyses of neuronal components of vHippo OTR+ circuit at synaptic, neuronal and behavioral levels aiming to uncover neuronal partnership between the hypothalamic OT system, vHippo and AOB and its role in the orchestration of socio-sexual behavior. Furthermore, our results will help to better understand mechanisms of sexual and social alterations in patients afflicted with mental pathologies, such as autism spectrum disorders.

• DFG Programme: Research Grants