# Cortical Synaptic Circuitry Underlying Visual Processing

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $412,500

## Abstract

Project Summary
This supplement is requested in response to NOT-AG-20-008 “Notice of Special Interest: Alzheimer's-focused
administrative supplements for NIH grants that are not focused on Alzheimer's disease”. The PI's parent grant
investigates the synaptic mechanisms, especially excitatory and inhibitory synaptic circuit mechanisms
underlying visual cortical processing in the mouse primary visual cortex (V1), using challenging techniques such
as in vivo whole-cell patch clamp recording and two-photon imaging guided patch recording, in normal healthy
mice. In the proposed extended research, we will apply the same techniques to disease models related to
Alzheimer's disease (AD). Malfunctioning of the blood-brain barrier (BBB) has been strongly implicated in
contributing to the onset and progression of AD. Since BBB is important for maintaining normal functioning of
neural circuits in the brain, pericyte diseases that cause BBB malfunction may result in abnormal neural circuit
computation and information processing even before neuronal degeneration, which is a hallmark of AD. Using
awake mouse visual cortex as a model system, we will test a central hypothesis that pericyte degeneration
initiates disruption of cortical information processing by selectively injuring some specific types of
cortical inhibitory neurons, resulting in alterations of the balance between excitatory (E) and inhibitory
(I) synaptic circuits and weakening of coordinated control of brain activity prior to neurodegenerative
changes. In collaboration with Dr. Berislav Zlokovic who is a renowned scientist in the field of pericyte
biology, BBB and AD, we will test this hypothesis in two BBB deficiency mouse models: inducible
pericyte-ablation model, and pericyte deficiency and rescue model. We will examine functional spiking
responses of excitatory and inhibitory neurons in V1 of these mouse models, as well as visually evoked
excitatory and inhibitory synaptic inputs to individual cortical neurons, at different disease progression stages.
Through the propose studies, we hope to generate an understanding of how changes in the E/I balance
contribute to the disruption of neural circuit computation in AD disease progression.

## Key facts

- **NIH application ID:** 10123775
- **Project number:** 3R01EY019049-13S1
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Huizhong Whit Tao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $412,500
- **Award type:** 3
- **Project period:** 2008-09-30 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123775

## Citation

> US National Institutes of Health, RePORTER application 10123775, Cortical Synaptic Circuitry Underlying Visual Processing (3R01EY019049-13S1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10123775. Licensed CC0.

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