# Bi-directional, task-dependent control of thalamic input gain, in layer 4c of the primary visual cortex, by the cholinergic and serotonergic neuromodulatory systems.

> **NIH NIH R01** · DUKE UNIVERSITY · 2021 · $451,040

## Abstract

PROJECT SUMMARY / ABSTRACT
Controlling the input that arrives at the primary visual cortex (V1) from the eyes is a powerful means for altering
the outcome of all subsequent processing of visual information. That the strength (or gain) of this visual input to
cortex can be dynamically modified is not controversial, but debate continues regarding the means by which
that gain control is achieved. Currently, there are well-described mechanisms for modifying the strength of
visual input based on other visual input (such as contrast gain control and normalization). However,
modification of cortical processing by behavioral and cognitive states (such as attention) almost certainly arises
from circuits outside the visual pathway, and we know far less about how this extra-retinal control of vision is
achieved. Anatomical studies in macaque monkeys indicate that modulation by the cholinergic and
serotonergic systems is strongly directed toward the site of visual input to cortex – the thalamic-recipient layer
(4c) in V1. This localization positions the cholinergic and serotonergic systems to control the extent to which
information from the eyes gets processed, and therefore whether and how it is perceived. We hypothesize that
acetylcholine and serotonin bi-directionally control the “gate” to cortex, such that acetylcholine increases (and
serotonin decreases) the strength of the input from the eyes. We will causally manipulate this modulatory
control of layer 4c during active vision, and determine the resulting effects on both neural responses and
behavior. At the neural level, we will determine the extent to which gain changes induced in layer 4c propagate
to other layers, including the conditions under which propagation occurs, and the form the propagated signal
takes. We will also determine the impact of these gain effects on behavior. Understanding how
neuromodulators allow state variables (such as arousal and motivation) to dynamically rebalance cortical
processing is critically important: Eight of the ten most-prescribed psychiatric drugs target neuromodulatory
systems, as does the only approved drug treatment for dementia. Thus, it is through controlling
neuromodulators that we (and the brain) modify perception, cognition, and behavior. It is generally assumed
that these drugs act by altering late-stage cortical processing, but the anatomy points us towards a concurrent
early modification of cortical input. We will elucidate the mechanism(s) behind, and determine the
consequences of, that early control upon which all later processing depends.

## Key facts

- **NIH application ID:** 10146401
- **Project number:** 5R01EY029663-03
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Anita A Disney
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $451,040
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10146401

## Citation

> US National Institutes of Health, RePORTER application 10146401, Bi-directional, task-dependent control of thalamic input gain, in layer 4c of the primary visual cortex, by the cholinergic and serotonergic neuromodulatory systems. (5R01EY029663-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10146401. Licensed CC0.

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