# Plasticity of cortical circuits in health, aging, and Alzheimer's disease

> **NIH NIH F99** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $46,752

## Abstract

Project Summary/Abstract
 Comprised of six distinct layers, the cerebral cortex is the key brain structure for all of our cognitive
abilities, ranging from sensation to decision making to movement. Each layer contains distinct cell types differing
in their genes, biophysical properties, and connectivity with other parts of the nervous system. Yet how these
diverse cortical layers and cell types are involved in any given behavior remains unresolved. Moreover, we
currently lack insight into how aging impacts interactions between cortical layers, which severely limits our
understanding of how aging alters cortical circuit function. At the most basic level, the cortex can be divided into
deep and superficial layers, each of which receives a complete copy of sensory information from the thalamus.
This suggests that the two sets of layers constitute different processing systems, which begs the question: what
are the possible purposes of these parallel networks? Because these processing streams differ in input, output,
intrinsic membrane, synaptic integration, and spike generation properties, I hypothesize that deep and superficial
layers have unique, independent functions. This also raises the intriguing possibility that these pathways are
differentially susceptible to aging. I hypothesize that aging leads to layer-specific changes that ultimately lead to
unique age-related deficits in cortical circuit function.
 Investigating the functions and age-related changes in deep and superficial cortical networks requires a
cortex-dependent task. In Dr. Bruno’s lab at Columbia University (F99), I developed a whisker-mediated texture
discrimination task for head-fixed mice, demonstrated that this behavior requires the cortex, and revealed that
both deep and superficial layers are involved in processing texture information (Aim 1.0, progress report). I
propose to characterize the sensorimotor strategies required for this behavior (Aim 1.1) and how layer-specific
manipulations alter texture representation in the deep and superficial layers (Aim 1.2). Understanding the
computations performed by individual layers will not only expand our understanding of the complex cortical
circuitry, but will also provide insight into how aging and neurodegeneration – which often involve dysfunction of
specific cortical cell types, layers, and their pathways – may be mitigated through the development of targeted
therapies. In Dr. Tsai’s lab at Massachusetts Institute of Technology (K00), I will develop a novel therapy that
galvanizes the brain’s own mechanisms to noninvasively improve cognitive and behavioral health in aged and
Alzheimer’s disease (AD) model mice. To do so, I will first identify how aging and AD alter learning, performance,
sensorimotor strategies (Aim 2.1), and sensory processing across cortical circuits (Aim 2.2) on my texture
discrimination task. These findings will inform the development of a noninvasive therapy that stimulates cortical
circuits to protect se...

## Key facts

- **NIH application ID:** 10488227
- **Project number:** 5F99AG073558-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Jung Man Park
- **Activity code:** F99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 5
- **Project period:** 2021-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10488227

## Citation

> US National Institutes of Health, RePORTER application 10488227, Plasticity of cortical circuits in health, aging, and Alzheimer's disease (5F99AG073558-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10488227. Licensed CC0.

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