# Molecular and cellular mechanisms of circuit evolution

> **NIH NIH K99** · ROCKEFELLER UNIVERSITY · 2022 · $100,000

## Abstract

Project Summary
 Regenerative therapies offer the potential to reverse deficits arising from neurodegenerative disease,
stroke, and traumatic brain injury. But the development of such treatments requires a comprehensive
understanding of how to direct neurons to adopt appropriate functional properties and circuit identities. This
proposal seeks to reveal fundamental principles of circuit design by identifying the permissible and
predisposed molecular mechanisms evolution uses to drive changes in the courtship behaviors of
drosophilids. Using a new model for comparative neurobiology that I have developed with my collaborators, I
will compare homologous neurons in the pheromone processing pathways of four closely related Drosophila
species. First, I will take advantage of highly stereotyped, species-specific pheromone preferences and in vivo
neuroimaging to identify the sites of adaptation in pheromone processing circuits. By quantifying the courtship
of each species in high resolution, I will be able to correlate differences in the pheromone preference behaviors
observed between species to the changes observed in how pheromone cues are processed (Aim 1). This will
elucidate the circuit motifs and dynamics that control the differential activation of an essential population of P1
interneurons that gate male entry into courtship across species. Next, to reveal the molecular underpinnings of
adaptations in P1 connectivity and excitability, I will perform RNA sequencing on the P1 neurons of each
species. This analysis will identify differentially expressed genes which I will test to determine how they
regulate the functional properties of P1 and mate preference behaviors (Aim 2). Finally, I will assess when and
how the transcription factor Fruitless–which specifies the male courtship circuitry–acts to organize the sexually
dimorphic anatomy and function of P1 neurons in melanogaster males. Further, taking advantage of genetic
pipelines I have built, I will use Targeted DamID to determine how changes in Fruitless target genes specify
novel courtship behaviors across species (Aim 3). Under the continued mentorship of Dr. Vanessa Ruta, and
supported by the substantial resources of Rockefeller University, I am well poised to complete the proposed
research and shed new light on the molecular and cellular mechanisms that evolution uses to encode novel
behaviors. In addition, a comprehensive career development plan, supported by my advisory committee, will
ensure that I receive the conceptual, technical, and career training I require to successfully transition to
independence at a top research institution.

## Key facts

- **NIH application ID:** 10440251
- **Project number:** 5K99GM141319-02
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Rory Tristan Coleman
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $100,000
- **Award type:** 5
- **Project period:** 2021-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10440251

## Citation

> US National Institutes of Health, RePORTER application 10440251, Molecular and cellular mechanisms of circuit evolution (5K99GM141319-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10440251. Licensed CC0.

---

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