Visual Experience is Necessary for Maintenance but not Development of Lateral Inhibition in Superior Colliculus

Author

Christine M. Otfinoski, University of Massachusetts AmherstFollow

Author ORCID Identifier

https://orcid.org/0000-0002-2248-7986

AccessType

Campus-Only Access for Five (5) Years

Document Type

dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Molecular and Cellular Biology

Year Degree Awarded

2024

Month Degree Awarded

February

First Advisor

Sarah L. Pallas

Subject Categories

Cell Biology | Molecular and Cellular Neuroscience

Abstract

Visual receptive fields (RFs) are composed of both excitatory and inhibitory areas, with lateral inhibition reducing the excitatory area and thus RF size. During development, RFs start out large and are then refined by a reduction in excitatory inputs and an increase in lateral inhibition. In some rodents, unlike cats and monkeys, sensory experience is not necessary for receptive field (RF) refinement but is required to maintain GABAergic inhibition and thus refined receptive fields throughout adulthood. In long-term dark-reared animals (LTDR), RF refinement is lost between post-natal (P) days 60 and 90. In LTDR animals, there is a reduction in the density of GABA-immunoreactive neurons compared to normally-reared (NR) animals post-P90. The loss of refinement can be prevented through light exposure prior to P60 or visual circuit activation between P33 and P40. Visual circuit activation using activation of TrkB, the receptor for brain derived neurotrophic factor (BDNF) results in maintained RF size through adulthood and increased levels of GAD (the rate-limiting enzyme for GABA production) protein levels. In this thesis work, we provide evidence of a strong temporal connection between neural activity and inhibition in sSC, lending support for the critical role of GAD- and GABA-immunoreactive (-ir) neurons in the long-term maintenance of RF refinement. We first interrogate the timeline in which GAD-ir and GABA-ir neuron density changes in NR and LTDR animals between P60 and P90. Immunohistochemistry is used to visualize and quantify the density and proportions of GABA-ir and GAD-ir neurons in sSC of NR and LTDR animals across ages between P40 and >P90. In long-term dark-reared (LTDR) animals, there is a decrease in GAD-ir and GABA-ir neuron density in the superior colliculus (SC) that occurs over the same time period (P60-P90) as a loss of RF refinement. This data suggests that there is a temporal connection between development and maintenance of lateral inhibition and receptive field size. Next, we investigate the mechanism by which LTDR animals given brief light exposure during a juvenile critical period (DR+) maintain RF size through adulthood. Immunohistochemistry is used to visualize and quantify the density and proportions of GAD-ir and GABA-ir neurons in DR+ animals during the light exposure period (P33-P40) compared to LTDR animals. In DR+ animals, there is an increase in GAD-ir neuron density that stabilizes GABA-ir neuron density throughout adulthood. When RFs are refined (in normally reared animals (NR) and animals briefly exposed to light as juveniles) the GAD-ir and GABA-ir neuron densities are stable, in contrast to densities in LTDR animals, in which RF refinement is lost and GAD-ir and GABA-ir neuron densities are reduced. These findings demonstrate temporal control over RF refinement by GAD and GABA, illustrating a critical role of inhibitory signaling in RF refinement development and maintenance and neural plasticity in adulthood.

DOI

https://doi.org/10.7275/36482841

Recommended Citation

Otfinoski, Christine M., "Visual Experience is Necessary for Maintenance but not Development of Lateral Inhibition in Superior Colliculus" (2024). Doctoral Dissertations. 3077.
https://doi.org/10.7275/36482841 https://scholarworks.umass.edu/dissertations_2/3077

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This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License