# CRCNS: Gradients of receptors underlying distributed cognitive functions

> **NIH NIH R01** · NEW YORK UNIVERSITY · 2020 · $155,806

## Abstract

A key goal of the NIMH is to define the mechanisms of complex behaviors. This necessitates an approach
that spans biological scales, but we have been lacking a single theoretical framework that links
neurotransmitter receptor function, large-scale patterns of brain activity and cognition. Working memory is a
key building block of cognition, but our understanding of why working memory emerges in sorne parts of
cortex, but not others, is limited. The macaque is an important model for studying higher cognitive function
with relevance to psychiatric disease, due to their intelligent behavior and relatively similar brains. We
propose the creation of a high-resolution 3D atlas of the macaque brain, and use it to create data-driven
neural circuit models that will give us key insights into the relationship between regional variations in
receptor densities and the emergence of distributed working memory. The atlas will enable quantification of
the regional and laminar distribution of 14 types of receptors (receptor fingerprints) and cell densities
across the entire macaque cortex. This will allow for interrogation of receptor fingerprints and cell densities
with submillimeler precision. It will be accompanied by a novel parcellation scheme based on the gradients
of cyto- and receptor-architecture across cortex. This atlas will be registered lo the NIMH Macaque
Template for easy integration with macaque /MRI data. We will identify the principal gradients that underlie
the distribution of receptors across cortex and compare these to hierarchies of sensory systems and
cognitive networks using open-access laminar tract-tracing and /MRI data. This approach will uncover the
receptor signature underlying distinct functional hierarchies. We will use the idea of bifurcations from
mathematics to interrogate how changes lo the density of receptors across cortex may lead to the
emergence of working-memory like persistent activity in particular regions of cortex. Crucially, we will allow
the experimentally measured receptor densities lo scale the effects of each receptor in each cortical area
and layer. We hypothesize that the pattern of working memory activity observed across cortical areas and
lamina depends critically on the regional distribution of the receptors. Further, we will expand our model to
include inter-areal connectivity data and investigate how release of neuromodulators can shift cortical
activity between cognitive networks. The results of our proposed research are likely to significantly advance
this area of research, with broad implications. The highly promising preliminary results have confirmed the
validity of the approach, ensuring that all aspects of the program have a high likelihood of success.
RELEVANCE (See instructions):
Cognitive symptoms of mental illnesses are difficult to treat, but can be the biggest impediment to patients
living independently. Cognitive functions rely on many brain areas communicating through chemicals and
receptors, ...

## Key facts

- **NIH application ID:** 10003395
- **Project number:** 5R01MH122024-02
- **Recipient organization:** NEW YORK UNIVERSITY
- **Principal Investigator:** XIAO-JING WANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $155,806
- **Award type:** 5
- **Project period:** 2019-08-27 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10003395

## Citation

> US National Institutes of Health, RePORTER application 10003395, CRCNS: Gradients of receptors underlying distributed cognitive functions (5R01MH122024-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10003395. Licensed CC0.

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