# Manipulating cellular excitability and CREB expression in CA1 to restore spatial processing in aged mice to young-like levels

> **NIH NIH F32** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $7,499

## Abstract

Project Abstract
Aging is inevitable, but maybe age-related cognitive decline does not have to be. Mild cognitive impairment
and dementia are prevalent in the elderly population, and even normal aging causes subtle decline in episodic
memory, making normal cognitive aging arguably the most widespread mental health issue in the developed
world. Spatial memory is an integral component of episodic memory and is particularly impacted by aging, but
the causes behind this deficit are unknown. Without understanding the mechanisms behind age-related spatial
memory decline, society will lack the means to overcome this obstacle to healthy aging or mitigate potential
risk factors for more serious disorders such as Alzheimer's disease. This proposal will pursue two possible
factors related to spatial memory dysfunction in a mouse model of aging and its conclusions could help
translate to potential avenues of intervention in humans. Preliminary data from the Cai lab and published data
has shown that, in CA1 of the hippocampus, cellular excitability and the transcription factor cAMP response
element binding protein (CREB) are reduced in aged rodents, impacting memory function. In these
experiments, increasing CA1 excitability and CREB expression ameliorated the memory deficits of these
animals. However, these studies were unable to verify whether the underlying neural memory representations
were improved by those manipulations. The overarching goal of this proposal is determine whether increasing
CA1 cellular excitability and CREB can restore spatial memory and neural representations to young-like levels.
In the first aim, I will use designer receptors exclusively activated by designer drugs (DREADDs) to increase
excitation coming into CA1 pyramidal cells in aged mice. Simultaneously, I will perform in vivo calcium imaging
during running on different linear tracks with specific reward locations for each track to quantify the accuracy of
neural spatial representations and spatial memory. In the second aim, I will use a viral approach to
overexpress CREB in CA1 pyramidal cells of aged mice while performing calcium imaging on the same task.
The findings from these aims will allow me to conclude whether increasing CA1 excitability or CREB can
improve spatial memory representations and deficits that arise from aging. By combining chemogenetics, viral
manipulations of protein expression, and in vivo imaging, this proposal will illuminate the neural mechanisms
behind age-related spatial memory decline.

## Key facts

- **NIH application ID:** 10428587
- **Project number:** 5F32AG067640-03
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** William Mau
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $7,499
- **Award type:** 5
- **Project period:** 2020-06-01 → 2022-06-10

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10428587

## Citation

> US National Institutes of Health, RePORTER application 10428587, Manipulating cellular excitability and CREB expression in CA1 to restore spatial processing in aged mice to young-like levels (5F32AG067640-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10428587. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*