# Development and Regulation of Emotion in Primates

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $739,797

## Abstract

PROJECT SUMMARY
Anxiety disorders can be severely debilitating, are prevalent in females, and represent a significant public
health burden. These disorders often begin with early-life dispositional anxiety that can lead to the
development of anxiety and depressive disorders and co-morbid substance abuse. New treatment strategies
aimed at early-life anxiety are needed and have the potential to prevent this life-long suffering. The nonhuman
primate (NHP) model of early-life anxious temperament (AT) is ideal because of similarities between rhesus
monkeys and humans in the development of socio-emotional behavior and its underlying neural circuits. Our
work, and that of others, strongly implicates altered function of the extended amygdala as a core feature of AT
and anxiety disorders. The extended amygdala includes the central nucleus of the amygdala (Ce) and the bed
nucleus of the stria terminalis (BST). The extended amygdala integrates threat-relevant information from
cortical and subcortical inputs, and initiates behavioral and physiological responses to threat. Of particular
interest are the orbitofrontal “regulatory” influences on extended amygdala function and anxiety. In considering
the development of new treatments, there are a number of critical questions. Advances in molecular
technologies for reversibly and bi-directionally controlling brain function are beginning to make some of these
questions tractable. Designer receptors exclusively activated by designer drugs (DREADDs) are ideal for
examining early-life AT in NHPs because they can modulate critical brain regions for long periods of time (i.e.
hours) -- particularly relevant for uncovering mechanisms related to mood and anxiety dysregulation. The
DREADDs technique involves infecting a brain region with a viral vector that expresses a receptor that does
not naturally occur in the brain, which is then combined with a pharmacological intervention, an otherwise
“inert” drug that selectively activates DREADDs. Importantly, DREADDs can be used to chronically alter circuit
function to model long-term brain alterations associated with psychopathology. We established a Cre-Lox
recombination strategy to express DREADDs in NHP amygdala neurons that project to select effector sites.
This allows unprecedented control of specific projections in the brains of freely behaving NHPs during
exposure to ethologically relevant contexts. This proposal will use DREADDs in young female NHPs to
understand how, early in life, projections in the extended amygdala drive sustained anxiety-related behavior
and how this circuit is modulated by direct projections from caudal orbitofrontal cortex. It will also explore
whether chronic early-life activation of the Ce is sufficient to induce extreme anxiety accompanied by the
functional and structural brain changes associated with stress-related psychopathology. Lastly, the proposed
studies will identify molecular markers of projection-specific anxiety-modulating neurons ...

## Key facts

- **NIH application ID:** 9851957
- **Project number:** 5R01MH046729-26
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Ned H Kalin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $739,797
- **Award type:** 5
- **Project period:** 1990-07-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851957

## Citation

> US National Institutes of Health, RePORTER application 9851957, Development and Regulation of Emotion in Primates (5R01MH046729-26). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9851957. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*