Molecular mechanisms underlying direction-selective circuit assembly and function in the mouse visual system

Active Project Grant Awarded Last action

Award ID
R01EY032095
Recipient
Awarding agency
Obligated
$6,017,638

Award facts

Assistance listing
93.867 Vision Research
Completion date 87% complete
Originally
Funding
  • $4,630,308.00 Federal
  • $1,387,330.00 Non-federal
Place of performance
Baltimore, MD 21218, USA

Award details come from USAspending.gov.

Description

Abstract
The elaboration of neural circuits involves a complex series of events, including neuronal differentiation, settling of neurons in appropriate locations, neural process outgrowth and pathfinding, target selection, synaptogenesis and synapse refinement. Development of direction-selective (DS) circuits in the mammalian visual system relies on precise execution of each of these steps, however we are only beginning to understand how these connections are established. The central goal of this proposal is to understand the molecular mechanisms that allow components of DS circuits to mediate appropriate visual system responses to image motion. DS responses depend critically on distinct classes of bipolar cells, starburst amacrine cells (sacs), and direction-selective retinal ganglion cells (dsgcs). The development of these neurons, including their differentiation and the regulation of their morphology and synaptic contacts, is integral to the generation of functional DS circuitry. Here, we propose leveraging our recent gene profiling and additional preliminary findings to address key unresolved questions in DS circuit wiring. Subtypes of dsgcs are tuned to motion in distinct preferred directions, and this is due to differences in asymmetric wiring of sacs onto the dendrites of these different dsgc subtypes; however, the underlying basis of this asymmetric SAC-dsgc wiring is unknown. We have identified genes that are differentially expressed in subtypes of dsgcs that are components of the accessory optic system (AOS): on-dsgcs (odsgcs) that differ only in their preferred directional preference-in this case for dorsal VS. Ventral object motion. Analysis of these differentially expressed (DE) genes has the potential to reveal underlying molecular mechanisms governing the development of these odsgcs and the synaptic wiring that determines their directional tuning, since the central difference between dorsal-odsgcs and ventral-odsgcs is the polarity of their preferred directional tuning. This proposal is focused on testing the hypothesis that differential gene expression in odsgcs of the accessory optic system (AOS) tuned to detect either upward or downward motion instructs the development of functional DS circuits.

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Subawards

Subrecipient Amount Awarded
The Regents Of The University Of California. San Francisco Molecular mechanisms underlying direction-selective circuit assembly and function in the mouse visual system $137,320
University Of California, Berkeley $67,058

Quick answers

Who received award R01EY032095?

R01EY032095 was awarded to The Johns Hopkins University by National Eye Institute (National Institutes of Health) on September 1, 2021.

How much is award R01EY032095 worth?

$6,017,638 has been obligated on R01EY032095: $4,630,308 in federal funding and $1,387,330 in non-federal funding.

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