# Neuron-glia interactions in Drosophila visual neuropiles

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2020 · $418,750

## Abstract

ABSTRACT
The long-term goal of the proposed research is to reveal how electrically non-excitable glial cells modulate
synaptic transmission in response to neuronal inputs using fly visual system as a model. Previous studies
on vision mostly have been focused on the visual transduction cascades and the neuronal circuits, whereas
our knowledge about the role of glial cells in vision is very limited. Neurobiological research in the last
decade has found that, In addition to their supportive role in neuron survival and function, the central
neuropil glia astrocytes can respond to various neurotransmitters, and likely modulate neuronal synaptic
transmissions. Neurotransmitter receptors are also detected in visual glia including Müller cells. However,
it remains to be elucidated how glia modulate synaptic transmission in visual system, and how this glial
function is controlled conversely by neurons.
To study this function of perisynaptic glia, we plan to use the Drosophila visual system as a novel model,
which allows genetic manipulation of signaling molecules specifically in glia or neuron, as well as
subsequent observation of neuronal activities via reporters in live animals with intact glial networks. In the
first visual neuropil region (lamina) of fly, photoreceptor axons release histamine upon light stimulation to
hyperpolarize projective large monopolar cells (LMC). All neuronal processes are wrapped laterally by three
epithelial glia cells (EG) in each laminar cartridge. We have previous found that EG concentrate a
glutamate-gated chloride channel GluCl in special membrane processes abutting terminals of T1
interneuron. Our preliminary study showed that loss of GluCl diminished the Ca2+ response of LMC to light
change, and impaired fly locomotion vision in dim conditions. Both dark-vision and electroretinogram
defects of the GluCl mutant were phenocopied by downregulation of a glutamate transporter EAAT1 in T1,
suggesting the involvement of T1 neuron and EAAT1 in the stimulation of GluCl. Finally, a cation channel
NA in T1 appeared to function upstream of GluCl as well. Based on these observations, we propose to test
a voltage-dependent, non-vesicular mechanism of neuron-glia communication, in which T1 neuron releases
glutamate through EAAT1 to open a GluCl-gated Cl- pool in EG, thereby facilitating the inhibition of LMC by
photoreceptors. This model may represent a general mechanism for interneuron to modulate synaptic
weight through glia in both flies and mammals, and may occur in central brain as well. Using a combination
of molecular and cell biological, genetic, histological, electrophysiological and in vivo imaging approaches,
we will specifically demonstrate that 1) a GluCl-gated glial Cl- pool is essential for the inhibitory visual
transmission; 2) T1 neuron releases glutamate through EAAT1 to open glial GluCl channel; and 3)
depolarization of T1 is required for EAAT1 to release glutamate.

## Key facts

- **NIH application ID:** 10000099
- **Project number:** 5R01EY027826-04
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** HONG-SHENG LI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $418,750
- **Award type:** 5
- **Project period:** 2017-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000099

## Citation

> US National Institutes of Health, RePORTER application 10000099, Neuron-glia interactions in Drosophila visual neuropiles (5R01EY027826-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10000099. Licensed CC0.

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