# Decoding the Mechanisms of Oxytocinergic Regulation in the Hippocamposeptal Circuit: Implications for Social Dysfunction in Alzheimer's Disease > **NIH NIH K01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $129,168 ## Abstract Project Summary/Abstract This K01 mentored training grant is designed to support Dr. Jinjing Liu in becoming an independent investigator in the Alzheimer’s disease (AD) field. The proposal’s scientific and training goals center on the study of the neurobiological basis of pathological social aggression in AD. Pathological social aggression appears in 30-50% of AD patients, impacting their quality of life, causing distress for caregivers, and imposing immense socioeconomic burden. Yet the neural mechanisms that contribute to social aggressive behavior, particularly within the context of AD, remain largely unknown and options to treat aggression in AD patients are limited. Under non-disease conditions, socially aggressive behavior is the result of complex signal integration involving information about internal state (social motivation, anxiety) and social stimuli (familiarity/novelty/threat perception). Classical lesion studies as well as more recent neurophysiological studies implicate the lateral septum (LS) in the control of this behavior. However, we do not understand the circuit-level mechanisms, nor do we know how AD-related pathology disrupts its function. This proposal’s overarching goal is to identify these circuits so that we may identify therapeutic targets for social dysfunction associated with AD. Existing literature and preliminary data support a hypothesis that AD-related pathology disrupts a specific extrahippocampal projection (CA2 to LSi pathway) by impairing neuropeptide oxytocin (OXT) function within this circuit. The proposed work will test this hypothesis by (1) establishing the role of the intermediate lateral septum (LSi) as a key integrator of cognitive information coming from the hippocampus (CA2) and OXT- sensitive inputs about internal motivation and anxiety state; (2) determining how AD-related pathology impacts CA2LSi circuitry to disrupt the normal regulation of social aggressive behavior; and (3) exploring the translational potential of enhanced OXT signaling in the LSi to restore circuit function and improve behavioral outcomes. The approach is innovative and achieves technical training goals by leveraging an array of modern neuronal recording and manipulation techniques, including Patch-seq, in combination with neural tracing and the use of a novel optically-sensitive caged OXT reagent developed in our lab that can achieve closed-loop spatiotemporal control over OXT release when combined with large-scale in vivo recording. The mentor team includes experts Dr. Richard Tsien (biophysics and synaptic physiology); Dr. Arjun Masurkar (clinical manifestations and mechanisms of AD); and Dr. György Buzsáki (systems and computational neuroscience). Building off extensive expertise in synaptic and ion channel physiology and animal behavior Dr. Liu will pursue this work under the guidance of her mentors to advance her long-term career goal of establishing an independent research program studying how neuromodulation at the mo... ## Key facts - **NIH application ID:** 10865991 - **Project number:** 1K01AG086573-01 - **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE - **Principal Investigator:** Jingjing Liu - **Activity code:** K01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $129,168 - **Award type:** 1 - **Project period:** 2024-07-01 → 2029-06-30 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10865991 ## Citation > US National Institutes of Health, RePORTER application 10865991, Decoding the Mechanisms of Oxytocinergic Regulation in the Hippocamposeptal Circuit: Implications for Social Dysfunction in Alzheimer's Disease (1K01AG086573-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10865991. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*