# INJURY-INDUCED SPATIAL MEMORY IMPAIRMENTS ARE LINKED TO UNCOORDINATED HIPPOCAMPAL NEURONAL FIRING

> **NIH NIH R01** · CHILDREN'S HOSP OF PHILADELPHIA · 2024 · $426,800

## Abstract

PROJECT SUMMARY
Traumatic brain injury (TBI) is the primary cause of death and disability in children and young adults1. TBI
afflicts more than two million people annually in the United States, with an estimated 5.3 million TBI survivors
living with lasting neurological impairments2,3. Mild TBI (mTBI) or concussion, accounts for nearly 90% of TBIs,
with symptoms including deficits in learning and memory that profoundly affect the daily life and overall health
of TBI survivors. Although TBI survivors suffer a range of cognitive impairments, deficits in learning and
memory are most common4–6. The hippocampus is critically involved in both of these phenomena and highly
susceptible to damage by TBI. Little is known about the precise mechanisms by which hippocampal damage
produces memory deficits. Our preliminary data indicate that spatial memory (a type of episodic memory
required for the discrimination of a spatially moved object), requires coordinated hippocampal theta and
gamma rhythms in the local field potential and neuronal firing time-locked to those rhythms (Figures 7-9 and
Innovation section below). Both of these required components are critically dependent on the activity of
inhibitory neurons, and specific inhibitory neurons in hippocampal area CA1 and the dentate gyrus (DG) are
significantly altered after TBI7,8. Based on these results we hypothesize that altered synaptic transmission
in specific hippocampal inhibitory neuron populations alters the balance between excitation and
inhibition (E/I balance), leading to local circuit dysfunction and significant weakening of the
coordinated hippocampal oscillations and neuronal firing required for normal spatial memory. To test
this hypothesis, in vivo and in vitro recordings together with chemogenetic manipulation of specific
subpopulations of inhibitory neurons in area CA1 and DG will be used to determine whether restoring normal
inhibitory neuron function will reinstate normal rhythms, time-locked action potential firing, and normal spatial
memory.

## Key facts

- **NIH application ID:** 10747862
- **Project number:** 5R01NS120099-03
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Akiva S Cohen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $426,800
- **Award type:** 5
- **Project period:** 2022-01-15 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10747862

## Citation

> US National Institutes of Health, RePORTER application 10747862, INJURY-INDUCED SPATIAL MEMORY IMPAIRMENTS ARE LINKED TO UNCOORDINATED HIPPOCAMPAL NEURONAL FIRING (5R01NS120099-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10747862. Licensed CC0.

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