# Aggression in Drosophila: circuitry involved; learning and memory accompanying aggression; and establishing the circuitry of high-level aggression in the brain

> **NIH NIH R35** · HARVARD MEDICAL SCHOOL · 2022 · $491,550

## Abstract

Project Summary:
Aggression is a normal innate behavior utilized for access to food, territory and mates by essentially all
species of animals, including humans. Levels of display of aggression vary widely among individuals,
however, and generally it is not known how much of this heterogeneity is genetic and how much is socially
induced. Probably both mechanisms influence the expression of the behavior in all organisms, with the
proportions of each varying widely between individuals. Unbridled aggression, in the form of violence, is a
peculiarly human manifestation of this behavior, and when one adds the use of weapons capable of inflicting
deadly damage to individuals and masses of individuals, it is a serious problem in society. Indeed weapons
allow the least fit of individuals to become dominant protagonists in our society. In animal species,
conspecifics sometimes kill opponents as well, but more commonly members of the same species engage
in ritualistic stepwise-increasing-intensity-displays of fighting abilities. The roots of aggression are biological
but there is little concrete information of how and where in the nervous system the seeds of violence are
sown. In this application we use a Drosophila model of aggression that we pioneered the use of. Of all the
available models, the Drosophila system offers the greatest ease and reproducibility of genetic manipulation
within the nervous system down to single identified neuron levels. These manipulations can readily be
combined with quantifiable behavioral measures in attempts to understand this complex behavior. Recently,
using an intersectional genetics strategy, we identified and manipulated single amine neurons in living
animals that are involved in aggression. For example, a single pair of serotonergic (5HT) neurons found via
this technique, facilitated going to higher levels of aggression during fights. With the first cycle of this
application, we unraveled some of the complex circuitry involved with this facilitation. This neuron innervates
a small visual area of a sensory integration center in the fly brain. The output of that region is a “switch” the
either enhances or reduces higher level aggression, and activation of that “switch” by 5HT release is the
enhancer element. Other recent studies showed that female flies also can fight at high intensity levels
(previously we thought that females fought only at low intensities) and two pairs of cholinergic neurons were
found only in female brains that are the keys to that decision. Other recent studies showed the flies, as
expected, use sensory cues in deciding how to behave (e.g., fight or court), but also watch and observe
what other animals are doing behaviorally in their decision making. In this proposal we continue these
studies by asking: how is high-level aggression triggered in male and female flies; how does the circuitry
differ in the two sexes; and how are the observed differences in sex-selective behavioral patterns generated....

## Key facts

- **NIH application ID:** 10488182
- **Project number:** 5R35GM118137-07
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Edward A Kravitz
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $491,550
- **Award type:** 5
- **Project period:** 2016-05-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10488182

## Citation

> US National Institutes of Health, RePORTER application 10488182, Aggression in Drosophila: circuitry involved; learning and memory accompanying aggression; and establishing the circuitry of high-level aggression in the brain (5R35GM118137-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10488182. Licensed CC0.

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