# Functional role of dual neurotransmission in aggression

> **NIH NIH R01** · MONTANA STATE UNIVERSITY - BOZEMAN · 2024 · $384,641

## Abstract

ABSTRACT
Dual neurotransmission has the potential to transform the way we consider neuronal signaling and the
transmission of information within circuits and networks. The importance of dual transmission is evident by
the large and increasing number of identified dual transmitting neurons in every system. However we still
have only limited insight into the regulation and functional effects of co-transmission. During our previous
funding period, we established: 1) the majority of octopamine (OA, the invertebrate analogue of
norepinephrine), neurons co-express glutamate, 2) OA and glutamate have overlapping, as well as distinct,
roles in reproductive and aggressive behaviors, and 3) manipulation of a glutamate-OA neuronal subset leads
to high intensity aggression. Although aggression is a critical component of social behavior observed across
species, when expressed at elevated levels aggression in humans can threaten lives and incur economic
burdens on society. Given the importance of maintaining a critical balance of aggression and
understanding the implications of dual transmission signaling in general, in this proposal we are
identifying the molecular and physiological mechanisms that constrain aggression as well as
dynamically regulate the release of co-transmitters. Leveraging our deep understanding of aggression-
promoting neurons, genetic tools, and functional imaging, we will test our hypothesis in three specific aims.
First, using fluorescent biosensors to visualize neurotransmitter release and Ca2+ imaging to quantify neuron
activity, we will test the hypothesis that glutamatergic and adrenergic receptors expressed by glutamate-OA
neurons are required for the regulation of co-transmission. Second, using epitope-tagged vesicular
transporters and antibodies we will test the hypothesis that sexually dimorphic glutamate-OA neurons exhibit
dynamic age-related changes in VGLUT levels. Finally, we will determine if VMAT-VGLUT terminal
phenotypes are dependent on external cues from postsynaptic neurons. The significance of our study is that
it addresses a fundamental neuroscience question, namely the molecular and potentially sexually dimorphic
regulation of the dual transmission phenomenon, as well as potentially leading to the targeting of the
glutamatergic system within glutamate-monoamine neurons as a therapeutic strategy for unchecked
aggression.

## Key facts

- **NIH application ID:** 10802317
- **Project number:** 5R01GM115510-07
- **Recipient organization:** MONTANA STATE UNIVERSITY - BOZEMAN
- **Principal Investigator:** Sarah J Certel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $384,641
- **Award type:** 5
- **Project period:** 2015-09-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10802317

## Citation

> US National Institutes of Health, RePORTER application 10802317, Functional role of dual neurotransmission in aggression (5R01GM115510-07). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10802317. Licensed CC0.

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