Date on Master's Thesis/Doctoral Dissertation

5-2023

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department (Legacy)

Department of Anatomical Sciences and Neurobiology

Department

Anatomical Sciences and Neurobiology

Degree Program

Anatomical Sciences and Neurobiology, PhD

Committee Chair

Bickford, Martha

Committee Co-Chair (if applicable)

Guido, William

Committee Member

Guido, William

Committee Member

McGee, Aaron

Committee Member

Magnuson, David

Committee Member

Borghuis, Bart

Author's Keywords

neuroscience; parabigeminal nucleus; neuroanatomy; synaptic properties; visual neuroscience; sensory neuroscience

Abstract

Subcortical structures of the visual system have been the subject of intense study in recent years, but there remain some important unanswered questions regarding the synaptic relationships linking the nuclei that comprise this important sensory network within the brain. In these studies, we use several modern and traditional approaches, including viral tract tracing, in vitro slice physiology, immunohistochemistry, optogenetics, and electron microscopy to characterize the circuits linking the superior colliculus (SC), parabigeminal nucleus (PBG), and lateral geniculate nucleus (LGN), with particular focus on GABAergic and cholinergic cell types. We found that the SC, an important visuomotor structure with connections to the LGN, PBG, pretectum, and pulvinar nucleus (among others), hosts a large and diverse population of GABAergic neurons that is composed primarily of interneurons labeled in the GAD67-GFP reporter mouse. Among these GABAergic cells residing within stratum griseum superficiale (SGS) of the SC, we found that GABAergic projection cells targeting the PBG exhibit unique characteristics, distinguishing them from other GABAergic projection populations as well as parvalbumin positive SC-PBG cells that exert opposing effects on postsynaptic cells in the PBG. Utilizing optogenetics in conjunction with whole-cell patch-clamp slice physiology, we additionally demonstrate a high degree of convergence between these opposing tectal inputs onto PBG neurons. Our electron microscopy experiments and lightlevel immunohistochemistry in GAD67 reporter mice also revealed a previously unidentified extra-tectal souce of GABAergic input to the PBG, where these inhibitory synapses were observed to account for almost half of its inputs. Finally, using MATH5-/- mutant mice that lack retinofugal projections, we identify the largely cholinergic inputs from the PBG as the likely source of “retinal replacement terminals” observed in the LGN in previous studies utilizing animal models of retinofugal input loss.

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