# Investigating abnormalities in top-down cortical processing and behavior in a model of the 22q11.2 deletion

> **NIH NIH R21** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2024 · $210,000

## Abstract

SUMMARY
Schizophrenia is a neuropsychiatric disorder that causes cognitive deficits and impairments in basic sensory
processing. Structural and functional imaging studies in schizophrenia patients suggest that a main structural
signature of schizophrenia is reduced long-range connectivity and disconnection between brain areas, however
how such reduced connectivity affects specific circuit components and cortical function remains largely unknown.
In this project, we will combine in vivo linear probe recordings with optogenetic modulation in the visual system
of the mouse model of 22q11 deletion syndrome to study altered bottom-up and top-down modulation of sensory
processing. In addition, recent transcriptomics studies have found that neurogliaform cells, a distinct class of
GABAergic inhibitory neurons, are the most affected class of neurons in schizophrenia. Neurogliaform cells
primarily reside in superficial layer 1 of the cortex and receive inputs from corticocortical axons, including
prefrontal cortical regions, from the thalamus and higher-order thalamic nuclei, and from subcortical
neuromodulatory populations, however the in vivo function of neurogliaform cells in health and their dysfunction
disease remains largely unknown due to lack of tools to specifically target them. To clarify the role of
neurogliaform cells in bottom-up and top-down processing, we will manipulate activity in neurogliaform cells
optogenetically in wild type and 22q11.2 mice and measure their effect on sensory processing. The research
proposed in this application is conceptually innovative and significant because it will give us a better
understanding of how bottom-up and top-down cortical processing and neural circuits involved in schizophrenia.
This work is also technically innovative because of the novel approaches to specifically target neurogliaform cells
and investigating their role in sensory processing in health and in the context of 22q11.2. Ultimately, such
knowledge has the potential to offer new opportunities for identification of biomarkers of disease and for
therapeutic interventions that target specific circuits.

## Key facts

- **NIH application ID:** 10832095
- **Project number:** 5R21MH133097-02
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Renata Batista-Brito
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $210,000
- **Award type:** 5
- **Project period:** 2023-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10832095

## Citation

> US National Institutes of Health, RePORTER application 10832095, Investigating abnormalities in top-down cortical processing and behavior in a model of the 22q11.2 deletion (5R21MH133097-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10832095. Licensed CC0.

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