# Mechanisms regulating formation and maintenance of sensory circuits

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $375,430

## Abstract

Presynaptic inhibitory synapses positioned across axon terminals of sensory neurons critically regulate
information flow across sensory circuits, allowing meaningful interactions of an organism with its external
environment. Whereas much is known about the functional role of presynaptic inhibitory synapses across
sensory circuits; little is known about the mechanisms that regulate the development, maturation and
maintenance of these inhibitory synapses. Using the well-characterized dim-light (rod) visual circuit of the
mammalian retina we uncovered a synaptic reorganization during assembly of GABAergic presynaptic inhibitory
synapses that regulate dim-light retinal output. The current proposal aims to determine the cell-autonomous and
non-cell autonomous mechanisms that regulate this developmental plasticity during assembly of inhibitory
feedback circuits that regulate the gain of sensory (retinal) signal transfer. Our research will yield fundamental
information about: (i) retinal circuit assembly (ii) organization of sensory circuits and mechanisms that regulate
sensory feedback, and (iii) principles that regulate receptor plasticity during establishment of inhibitory circuits
across the CNS. We will combine murine transgenic approaches with high resolution light microscopy, 3D
electron microscopy and electrophysiology to address the following three Aims. In Aim 1 we will determine if cell-autonomous alterations in chloride transporter expression across developing retinal rod bipolar neurons drive
and regulate the timing and/or occurrence of the developmental GABAA receptor reorganization. Aim 2 will
determine the contribution(s) of excitatory and inhibitory neurotransmission onto the retinal rod bipolar neuron in
regulating the developmental GABAA receptor plasticity. Aim 3 will determine the role of early visual experience
in regulating GABAA receptor reorganizations and assembly of feedback inhibitory synapses of the dim-light
retinal circuit. Our research will reveal the interplay between cell-autonomous mechanisms, synaptic input,
network activity and environmental cues during establishment and maturation of feedback inhibitory circuits that
regulate sensory output. Our study will also reveal circuit plasticity motifs that can be recruited to ameliorate
dysfunction during retinal diseases. Furthermore, our findings will determine the developmental sequence of
maturation during assembly of invivo presynaptic inhibitory circuits to compare with exvivo retinal assembly such
as when pluripotent stem cells are used for retinogenesis.

## Key facts

- **NIH application ID:** 10891471
- **Project number:** 5R01EY031677-05
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Mrinalini Hoon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $375,430
- **Award type:** 5
- **Project period:** 2020-09-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10891471

## Citation

> US National Institutes of Health, RePORTER application 10891471, Mechanisms regulating formation and maintenance of sensory circuits (5R01EY031677-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10891471. Licensed CC0.

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