# Septohippocampal circuit deep brain stimulation for selective RDoC aspects of cognition

> **NIH NIH K08** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2023 · $196,326

## Abstract

Project Summary
The septohippocampal circuit plays a crucial role in multiple cognitive Research Domain Criteria (RDoC) domains,
including memory, attention, anxiety, and sensorimotor processing. This circuit is comprised primarily of the medial
septal nucleus (MSN), hippocampus and medial prefrontal cortex (mPFC). Pharmacological and genetic models targeting
glutamate N-methyl-D-aspartate (NMDA) receptor hypofunction within this circuit result in memory deficits, difficulty
with attention, and social interaction impairments. Therefore, we are studying the relationship between MSN-mPFC-
hippocampal oscillatory activity in NMDA receptor hypofunction models to better create treatments for disrupted theta
and gamma oscillations which are altered in a variety of psychiatric disorders. Recent evidence suggests that deep brain
stimulation (DBS) may be one such promising treatment modality for circuit disorders. This NIMH K08 Career
Development Award will provide the necessary foundation for Darrin J. Lee, MD, PhD to pursue the development of
novel DBS techniques for septohippocampal circuit disorders. The project and training plan are rooted in the
electrophysiological and molecular underpinnings of NMDA receptor hypofunction, while concomitantly enabling the
candidate to collaborate with and learn from his mentors and consultants. This program will enable him to supplement his
current skillsets in areas where he has identified gaps in his knowledge base, including relevant research methodology,
study design, machine learning, and structural connectivity. The proposed research will focus on 1) characterizing neural
oscillations within the septohippocampal circuit in two complementary models of NMDA receptor hypofunction
(pharmacological: chronic MK-801 administration and genetic: parvalbumin interneuron-selective NR1 knockout); 2)
evaluating the cognitive effects of DBS in these rodent models, and 3) evaluating the relationship between
electrophysiological biomarkers and behavior using machine learning. The interpretation of data from this research will
improve understanding of specific electrophysiological aspects of impaired brain function in septohippocampal circuit
disorders and serve as a catalyst for a research program centered on neuromodulation for these disorders. Moreover, data
collected, skills procured, and collaborations developed will enable Dr. Lee to seek R01 funding and obtain career
independence. Taken together, the data collected, and training developed will ultimately facilitate development of an
investigator with unique skills in service of ameliorating suffering caused by septohippocampal circuit disorders.

## Key facts

- **NIH application ID:** 10652984
- **Project number:** 5K08MH121757-04
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Darrin Jason Lee
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $196,326
- **Award type:** 5
- **Project period:** 2020-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10652984

## Citation

> US National Institutes of Health, RePORTER application 10652984, Septohippocampal circuit deep brain stimulation for selective RDoC aspects of cognition (5K08MH121757-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10652984. Licensed CC0.

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