# Patterned, Stimulus-Independent Neuronal Activity In the Developing Drosophila Visual System: Origin and Contribution to Synaptic Maturation

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $28,873

## Abstract

Research and Career Plan
Summary of Parent Award
 Synaptic connections determine how neural circuits process information. Understanding how the strength
and specificity of these connections is established is a central challenge in neurobiology. In many parts of the
developing mammalian brain, stereotyped patterns of stimulus-independent neuronal activity precede sensory-
driven responses. Whether and how this developmental activity guides synapse assembly at the level of defined
cell types and circuits is not well-understood. Here, much of the challenge is due to the size and complexity of
the mammalian brain itself: Even in the retina, where developmental activity is best characterized, the technical
barriers to pursuing synapse level questions are significant. We recently discovered analogous patterned,
stimulus-independent neural activity (PSINA, pronounced ‘see-nah’) in the developing Drosophila brain. With the
ever-growing knowledge of its neurobiology, spanning the connectome to behavior, the fly is unmatched in its
promise for cell type- and circuit- level studies. PSINA is globally coordinated with brain-wide, periodic active
and silent phases. In the visual system, each cell type participates in PSINA with distinct and stereotyped spatio-
temporal patterns of activity. These developmental activity patterns are correlated between pairs of neurons
known to be synaptic partners in the adult. Our long-term goal is to test the hypothesis that the cell-type-specific
activity patterns of PSINA refine the emerging connectome to generate wild-type synaptic strength and
specificity. Here, we will work toward this goal by leveraging a new genetic handle on PSINA: Trpγ, a cation
channel with a weak preference for Ca2+, is required for wild-type PSINA. In trpγ mutants, the amplitude of activity
is reduced by >50% across the whole brain, and cell-type-specific activity patterns and synapse numbers are
altered. Trpγ is expressed in <1.5% of the neurons in the brain. Notably, silencing only these neurons by
overexpressing a hyperpolarizing channel attenuates PSINA by >90%. This indicates that some or all of this
diverse group of ~2,000 Trpγ-expressing (i.e., Trpγ+) neurons are critical to coordinating PSINA in the developing
brain. We hypothesize that Trpγ+ neurons are the source of the cell-type-specific activity patterns. In Aim 1, we
will identify individual Trpγ+ neurons that innervate the visual system and test if these neurons specify the activity
patterns of their post-synaptic partners. Determining the origin of these patterns will allow us to ask whether they
are the cause or consequence of synapse and circuit maturation. In Aim 2, we will focus on a specific neuron
that is part of the well-studied motion detection circuit and ask if the strengths of its post-synaptic contacts are
altered in trpγ mutants. Identifying the cellular origin of the activity patterns and understanding the effect of PSINA
on synaptic development will allow us to rever...

## Key facts

- **NIH application ID:** 10570671
- **Project number:** 3R01NS123376-01S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Orkun Akin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $28,873
- **Award type:** 3
- **Project period:** 2022-04-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10570671

## Citation

> US National Institutes of Health, RePORTER application 10570671, Patterned, Stimulus-Independent Neuronal Activity In the Developing Drosophila Visual System: Origin and Contribution to Synaptic Maturation (3R01NS123376-01S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10570671. Licensed CC0.

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