# CRCNS: Theory-guided studies of cortical mechanisms of multi-input integration

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $386,514

## Abstract

A fundamental goal for understanding the brain and mammalian and human intelligence, and to understand
how processing goes awry in genetic and developmental diseases, is to understand the principles of
operation of cerebral cortex. A key step is to understand "canonical" operations carried out by cortex. Here
we will explore the operations of cortical circuitry in experiments guided by a new theory of a candidate
canonical circuit operation. Sensory cortex must globally integrate localized sensory input to parse objects
and support perception. In individual neurons, this manifests as modulation of responses to local stimuli by
context or top-down influences such as attention and as interactions between local stimuli in driving
responses ("normalization"). These interactions tend to be suppressive for stronger stimuli but more weakly
suppressive or facilitative for weaker stimuli. Recent theoretical work in Dr. Miller's lab has proposed a
novel cortical circuit motif, the stabilized supralinear network (SSN), that provides a simple unified
explanation for a wide variety of neural responses related to global integration. The model serves as a
guide for new experimental explorations of cortical circuitry in Dr. Van Hooser's laboratory, using both
traditional experimental recording techniques and his recently developed novel optical methods for
manipulating cortical activity with high spatial and temporal resolution. The SSN model, if successful, will
be elaborated to best explain experimental results. In Aim 1, the light-activated channel channelrhodopsin2
(ChR2) and an optical stimulation system are used to drive activity of cortical circuits in precise spatial and
temporal patterns to test the contribution of cortical circuits to normalization and contextual modulation
including various SSN predictions about them. In Aim 2, the balance of drive to excitatory (E) vs. inhibitory
(I) cells within the cortex will be altered using viruses that largely restrict expression of ChR2 to E or I cells.
This will test SSN model predictions involving modulation of network gain by modulatory input biased
toward E or I cells, mechanisms of attentional modulation, and the dependence of a "paradoxical" result -­
adding drive to I cells reduces steady-state I responses -- on the spatial pattern of drive to I cells and level
of cortical activation.
RELEVANCE (See instructions):
 We will test the predictions of a powerful framework for understanding how sensory cortex globally
 integrates multiple sources of input, bottom-up and top-down, to produce neuronal responses and
 ultimately perception. Understanding circuit changes that cause breakdown of this cortical operation may
 provide insight into disorders such as autism and schizophrenia, which show deficits in contextual or global
 processing. Understanding global integration will be necessary for the creation of prosthetic devices to treat
 blindness and other disorders.

## Key facts

- **NIH application ID:** 9997942
- **Project number:** 5R01EY029999-03
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** KENNETH D MILLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $386,514
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9997942

## Citation

> US National Institutes of Health, RePORTER application 9997942, CRCNS: Theory-guided studies of cortical mechanisms of multi-input integration (5R01EY029999-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9997942. Licensed CC0.

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