June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
A novel thalamic-centric model for visual critical period plasticity
Author Affiliations & Notes
  • Eric Horstick
    Biology, West Virginia University, West Virginia University, Morgantown, WV, US, academic, West Virginia, United States
  • Footnotes
    Commercial Relationships   Eric Horstick None
  • Footnotes
    Support  P20GM144230 VS-CoBRE
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 4382. doi:
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      Eric Horstick; A novel thalamic-centric model for visual critical period plasticity. Invest. Ophthalmol. Vis. Sci. 2023;64(8):4382.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : During the visual critical period, sensory experience refines the structure and function of visual circuits. Disruption to visual input during the critical period can lead to amblyopia and sustained visual impairment. The basis of this plasticity was long thought to be limited to cortical circuits, yet recently described thalamic ocular dominance plasticity challenges this dogma and demonstrates greater complexity underlying visual plasticity. Yet how visual experience modulates responses of thalamic neurons or how the thalamus modulates CP timing is incompletely understood. The simple visual circuitry and natural absence of a cortex makes zebrafish an ideal thalamus-centric model to understand subcortical mechanisms of critical period regulation and visual plasticity.

Methods : We have developed novel behavioral assays to control visual experience in larval zebrafish and demonstrate a developmental critical period where visual experience drives neural and behavioral change. We combine calcium imaging, glutamatergic imaging, optogenetics, and pharmacology to assess neural physiology in vivo and with neuron level resolution.

Results : In our thalamus-centric model, we show that visual experience leads to sustained changes in a subset of genetically defined thalamus neurons, which we call AMNs, to regulate visually-mediated behavioral performance - specifically the turning direction during an easily screened visually evoked search behavior. Moreover, hemisphere-specific functional changes in AMNs correlate with changes in visuomotor behavior, establishing a role of thalamic plasticity in modulating motor performance. Last, we show that the timing of thalamic plasticity is established by inhibitory signaling.

Conclusions : Together, our work demonstrates that visual plasticity is more broadly conserved and shows that visual experience leads to neuron-level functional changes in the thalamus that require inhibitory signaling to establish critical period timing. Further, our work establishes zebrafish as a powerful model to study thalamuc visual plasticity, which is amendable to high throughput genetic and pharmacological screening, which will pave the way to identity theraptuics to modulate visual plasticity and favor repair.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

 

Model of visual plasticity in zebrafish. Yellow represents visually stimulated eye.

Model of visual plasticity in zebrafish. Yellow represents visually stimulated eye.

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