Date on Master's Thesis/Doctoral Dissertation

12-2025

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Anatomical Sciences and Neurobiology

Degree Program

Anatomical Sciences and Neurobiology, PhD

Committee Chair

Bickford, Martha

Committee Member

Guido, William

Committee Member

Krimm, Robin

Committee Member

Cang, Jianhua

Committee Member

Borghuis, Bart

Author's Keywords

neuroscience; superior colliculus; mouse

Abstract

The visual thalamus is influenced by a diverse array of cortical and subcortical inputs that shape how information is transmitted to cortex. Using a variety of anatomical, optogenetic, and in vitro physiological techniques I investigated the differential impacts of modulation and integration of first and higher-order thalamic nuclei, while relying on influential concepts on the general organization of thalamic nuclei. In the first data chapter, I determined how GABAergic pretectum (PT) projections to the dorsal lateral geniculate nucleus (dLGN) and visual thalamic reticular nucleus (vTRN) can influence retinogeniculate signal transfer. We found that the PT provides over 75% of the GABAergic, and over 30% of the total synaptic input to the vTRN. Optogenetic activation of PT terminals reduced the firing frequency of vTRN neurons as well as the amplitudes of their postsynaptic responses to primary visual cortex (V1) input. In the dLGN, synaptic terminals originating from the PT targeted interneurons more frequently than thalamocortical (relay) cells, and optogenetic activation of PT input had a greater impact on interneuron firing frequency compared to relay cells. This cell type specific impact of PT input to the dLGN resulted in the disinhibition of relay cells and an increase in the amplitude of their postsynaptic responses to retinal input. In the second data chapter, we show that WFV inputs to the pulvinar (PUL) define two subregions; a caudal medial region (Pcm) that receives bilateral nontopographic WFV input and a lateral region (Pl) that receives ipsilateral topographic WFV input. Electron microscopy revealed that terminals arising from WFV neurons are similar in size across both PUL subdivisions; they are significantly larger than terminals originating from cortical layer 6 (L6) and significantly smaller than terminals originating from cortical layer 5 (L5). Optogenetic activation of WFV terminals in the Pcm evoked responses that displayed short-term synaptic facilitation, similar to responses to photoactivation of L6 inputs, whereas responses in the Pl displayed short-term synaptic depression similar to responses to photoactivation of L5 inputs. Finally, employing dual-opsin optogenetics, we found a high degree of convergence of ipsilateral and contralateral WFV and L5 and L6 input on individual PUL neurons in both the Pcm and Pl. Collectively, these studies reveal complementary mechanisms by which subcortical inputs to the visual thalamus interact with cortical pathways: excitatory convergence in the PUL integrates spatially and functionally distinct inputs, while inhibitory PT projections to the dLGN and vTRN enhance retinal signal throughput via targeted disinhibition. Both mechanisms highlight the thalamus as an active processor, rather than a passive relay, of visual information.

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