# Development and Regulation of Emotion in Primates

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $766,910

## Abstract

PROJECT SUMMARY –
New treatments for anxiety disorders are critically needed as numerous individuals fail to respond to current
treatments. A more complete understanding of pathological anxiety at the molecular, cellular and circuit levels
will provide a foundation for new treatment development. In this regard, nonhuman primate (NHP) models are
invaluable for understanding mechanisms underlying maladaptive anxiety relevant to stress-related
psychopathology. An important recent advance is the use of chemogenetic methods to modulate the primate
amygdala. This work serves as an initial foundation for treatment development directed at the regulation of
subcortical regions relevant to the pathophysiology of psychiatric disorders.
 As a translational bridge, our laboratory employs methods that provide an in-depth mechanistic
understanding of brain alterations associated with extreme anxiety, including behavioral phenotyping, functional
and structural neuroimaging, RNA sequencing and viral vector-mediated gene delivery. Findings from our
chemogenetic studies using Designer Receptors Exclusively Activation by Designer Drugs (DREADDs) point to
basolateral amygdala (BLA) neurons as potential treatment targets. The BLA processes threat-related
information received from cortical and subcortical sources and transmits this information to the extended
amygdala (central nucleus of the amygdala (Ce) and bed nucleus of the stria terminalis), which activates threat-
related responses via its downstream targets. Within the BLA, inhibitory interneurons modulate the function and
output of longer-range projecting excitatory neurons, which project to the Ce, other subcortical structures, and
posterior orbitofrontal cortex (pOFC). The overall aims of this proposal are to further understand the implications
of amygdala modulation in relation to treatment development focusing on BLA neurons. Neuroimaging and RNA
sequencing (RNA-Seq) will provide insights into mechanisms related to therapeutic efficacy. Additionally, these
studies will serve as a proof-of-concept to understand the feasibility of developing chemogenetic approaches for
the future treatment of severe and refractory psychiatric disorders.

## Key facts

- **NIH application ID:** 10445802
- **Project number:** 2R01MH046729-28
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Ned H Kalin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $766,910
- **Award type:** 2
- **Project period:** 1990-07-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10445802

## Citation

> US National Institutes of Health, RePORTER application 10445802, Development and Regulation of Emotion in Primates (2R01MH046729-28). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10445802. Licensed CC0.

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