Role of VIP Interneurons in Modulating Hippocampal Circuit Output and Behavior

• Applicant: Professor Dr. Imre Vida
• Subject Area: Experimental and Theoretical Network Neuroscience ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 546685760

The subiculum, a part of the hippocampal formation, serves as the final gate for the hippocampal output and has been implicated in cognitive and emotional deficits. Increased activity in the ventral subiculum has been detected in rodent models of schizophrenia. These models exhibit impaired sensorimotor gating, as tested using the pre-pulse inhibition paradigm, and increased spontaneous locomotor activity, as observed in open-field tests. Dysfunction in GABAergic interneurons (INs) has been shown to contribute to this hyperactivity and the resultant increase in output from the hippocampal formation. However, the neural mechanisms underlying the increased activity in the subiculum are not well understood. Vasoactive intestinal peptide-expressing (VIP+) cells, a class of GABAergic INs that preferentially target other subtypes of GABAergic INs, provide network disinhibition in the hippocampus and neocortex. Although altered VIP signaling has been implicated in schizophrenia pathophysiology, the functional role of subicular VIP+ INs in regulating network activity and behavior is largely unexplored. Our preliminary data revealed that VIP+ INs show a particularly high abundance in the subiculum. Therefore, we hypothesize that VIP+ INs could modulate the output of the hippocampal formation by inhibiting other INs, thereby producing disinhibition of principal neurons. In this proposal, therefore, we aim to employ optogenetic and chemo-genetic manipulation techniques, combined with behavioral, electrophysiological and neuroanatomical approaches, to investigate the structural organization and physiology of VIP+ IN subnetwork and its involvement in behavior. Focusing on the ventral subiculum, we define four specific aims: (1) Analyze the cellular morphology, intrinsic physiological properties and connectivity of ventral subiculum VIP+ INs; (2) To characterize the functional role of VIP+ INs in modulating ventral subiculum output; (3) Map the synaptic and modulatory inputs onto ventral subiculum VIP+ INs; (4) To delineate the activity of ventral subiculum VIP+ INs in behaviors relevant to cognition and emotion.

• DFG Programme: Research Grants
• International Connection: Taiwan
• Partner Organisation: National Science and Technology Council (NSTC)
• Cooperation Partner: Professor Cheng-Chang Lien, Ph.D.