# Mechanisms regulating the maturation of prefrontal top-down circuitry in control of attentional behavior

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $551,473

## Abstract

Cognitive function relies on the cohesive activity of large-scale networks. Long-range cortico-cortical
projections facilitate such network activities by integrating information from various inputs and then relaying it
to other cortical regions. Of particular significance is the evolutionarily conserved top-down projection from
prefrontal cortex (PFC) to sensory visual cortex (VIS) which integrates sensory, motor, and cognitive
information to modulate sensory processing. Conserved PFC->VIS projections regulate VIS responses to
visual stimuli in attention based tasks in macaque, and optogenetic manipulation in mice shows that this circuit
can enhance visual discrimination sensitivity. Notably, deficits in PFC modulation of VIS activity are pervasively
reported in neurodevelopmental and psychiatric disorders, and often emerge following childhood and
adolescence. Yet limited knowledge of processes governing long-range cortical circuit development hinders
further pathophysiological insight into these conditions. The goal of this study is to identify the developmental
mechanisms of PFC circuitry that mediate top-down control of attentional network and behavior. Here we test
the hypothesis that top-down PFC->VIS cortical circuits require a Lynx1, developmentally regulated nicotinic
modulator,-dependent adolescent shift in the balance of local/long-range inputs to coordinate temporal
dynamics between PFC and VIS modulate attentional behavior, and that Lynx1 modulation can ameliorate top-
down circuit deficits in mice with a risk gene of neurodevelopmental disorders. We will test his hypothesis by
integrating techniques to measure and manipulate neural activity and gene expression within specific circuits of
mice tested in a translationally-relevant touchscreen system to assess attention during naturalistic freely-
moving behavior.

## Key facts

- **NIH application ID:** 10155558
- **Project number:** 5R01MH119523-03
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Hirofumi Morishita
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $551,473
- **Award type:** 5
- **Project period:** 2019-07-05 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10155558

## Citation

> US National Institutes of Health, RePORTER application 10155558, Mechanisms regulating the maturation of prefrontal top-down circuitry in control of attentional behavior (5R01MH119523-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10155558. Licensed CC0.

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