P3.33. ELECTROPHYSIOLOGICAL AND BEHAVIORAL INSIGHTS INTO THE IPN-VHPC CIRCUIT UNDERLYING SOCIAL STRESS RESPONSES
Sylwia Drabik1,2, Gabriela Stopka1,2, Aleksandra Trenk1, Patryk Sambak1,2, Gabriela Czerniak1, Aya Dridi2, Kinga Przybylska1,2, Anna Blasiak1
1 Department of Neurophysiology and Chronobiology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Krakow, Poland
2 Doctoral School of Exact and Natural Sciences, Jagiellonian University, Kraków, Poland
INTRODUCTION: The interpeduncular nucleus (IPN) is a key regulator of anxiety and social behavior, characterized by a dense expression of the TrkA receptors, which bind nerve growth factor (NGF). Social stress enhances brain NGF levels, modulating IPN activity. The IPN forms functional connection with the ventral hippocampus (vHPC), a hub for social and anxiety-related signalling and a source of NGF.
AIM(S): Despite emerging evidence of the IPN–vHPC interaction, the specific behavioral and mechanistic contributions of this pathway remain unclear. Therefore this study aimed to characterise IPN neurons innervating the vHPC at electrophysiological and functional levels.
METHOD(S): Electrophysiological properties and NGF sensitivity of IPN neurons were examined using whole-cell patch clamp and multielectrode array recordings (MEA). Viral based tract-tracing was employed to characterize IPN-vHPC innervation. Resident intruder test was used to determine if IPN neurons innervating vHPC encode aggression-related information.
RESULTS: Whole-cell patch clamp recordings from slices containing the anterior IPN revealed no detectable response to NGF application. Tract-tracing studies identified numerous cells innervating the vHPC, particularly within the rostral (IPR) and lateral (IPL) subnuclei of the IPN. To further characterize this population, a series of experiments incorporating optogenetic tagging were conducted, revealing a subset of neurons responding with inward whole-cell currents to NGF administration. Complementary MEA recordings demonstrated both inhibition and excitation of IPN neurons after NGF application. The resident-intruder test revealed increased c-Fos expression in the group exposed to resident’s smell and after social defeat, identifying the activation of a distinct neuronal population in IPR.
CONCLUSIONS: Our findings unveil direct innervation of the vHPC by IPN subnuclei, along with NGF-mediated modulation of a subset of IPN neurons. Notably, the IPR appears to be selectively activated by social stress.
FINANCIAL SUPPORT: National Science Centre, Poland (UMO 2021/41/N/NZ4/04499; UMO- 2023/49/B/NZ4/01885) RSM grant, UJ (U1U/W18/NO/28; U1U/W18/NO/28.55)