# Beyond the classic VTA:  extended amygdala influence on DA subcircuits in primate

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2021 · $370,305

## Abstract

PROJECT SUMMARY
 Emotional dysregulation and altered dopamine (DA) function occur in many psychiatric disorders. A
central goal of our research program has been to understand how the amygdala, a key regulator of emotion,
afferently influences DA function at the cellular level in primates. In the previous funding period, we found that
amygdala-central extended amygdala (CEA) paths target DA subpopulations that lie mainly outside the ‘classic
ventral tegmental area (VTA)’, with downstream effects on ‘limbic-associative’ striatum.
 The CEA mediates various stress-induced behaviors, and has a high content of neuropeptides,
including corticotropin releasing factor (CRF). Stress-induced activation of the CEA and/or manipulation of
CRF in the CEA, has downstream effects on DA cells, and precipitates lasting changes in goal-directed
responses such as drug seeking, social responses, and compulsive behavior. Very little work has been done
on understanding this model in higher primates, in part because of lack of a detailed circuit map at the ‘meso-
anatomic’ level. In mapping the CEA-DA-striatal path in nonhuman primates we found that the CEA has a
strong input to parabrachial pigmented nucleus (PBP) and A8 neurons (i.e. DA subgroups outside midline
(‘classic’) VTA). While usually not a subject of research, these DA neuronal groups are disproportionately
expanded in human and nonhuman primates. We also found that 1) the CEA projection is subdivision-specific,
2) CRF is highly expressed in CEA-DA afferent inputs, and, 3) CEA-DA afferent paths are associated with
specific efferent paths to striatal regions outside the ‘classic’ nucleus accumbens. Thus, a CRF-enriched CEA-
DA circuit projects largely outside the ‘classic (medial) VTA’ (mesolimbic) path, to modulate central/caudal
ventromedial (‘limbic-associative’) striatum.
 In this proposal, we will examine the on CEA-DA-striatal circuit at a more ‘high resolution’ level to
understand cell-type specific connections to and from the key DA neuronal populations that are involved in the
nonhuman primate: the PBP and A8 subgroups. After quanitifying CRF contacts (from all sources) on DA
versus non-DA cells (AIM 1a), we will examine 1) the extent to which glutamate, GABA, or both exist in the
CEA-DA path, and their co-expression with CRF (AIM 1b), 2) the extent to which the CEA targets DA neurons,
non-DA neurons, or both (AIM 2), 3) whether striatal-projecting neurons in the PBP and A8 receive direct CEA
contacts (AIM 3).

## Key facts

- **NIH application ID:** 10114331
- **Project number:** 5R01MH115016-04
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** JULIE L. FUDGE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $370,305
- **Award type:** 5
- **Project period:** 2018-06-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10114331

## Citation

> US National Institutes of Health, RePORTER application 10114331, Beyond the classic VTA:  extended amygdala influence on DA subcircuits in primate (5R01MH115016-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10114331. Licensed CC0.

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