Date on Master's Thesis/Doctoral Dissertation

8-2018

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Anatomical Sciences and Neurobiology

Degree Program

Anatomical Sciences and Neurobiology, PhD

Committee Chair

Guido, William

Committee Co-Chair (if applicable)

Bickford, Martha

Committee Member

Bickford, Martha

Committee Member

Krimm, Robin

Committee Member

Mellen, Nicholas

Committee Member

Borghuis, Bart

Committee Member

Lundy, Robert

Author's Keywords

dorsal lateral geniculate nucleus; thalamic reticular nucleus; acetylcholine; nicotinic; muscarinic

Abstract

Cholinergic signaling plays a vital role in modulating the flow of sensory information through thalamic circuits in a state-dependent manner. In the dorsal lateral geniculate nucleus (dLGN), the thalamic visual relay, release of acetylcholine (ACh) contributes to enhanced thalamocortical transfer of retinal signal during behavioral states of arousal, wakefulness, and sleep/wake transitions. Moreover, ACh modulates activity of the thalamic reticular nucleus (TRN), a structure which provides inhibitory input to dLGN. While several cholinergic nuclei have been shown to innervate dLGN and TRN, it is unclear how projections from each area are organized. Furthermore, little is known of how or when cholinergic fibers arrive and form functional synapses during development. To address these questions, we used a genetically modified mouse (ChAT-Cre) mouse to selectively visualize cholinergic projections to dLGN and TRN. We conducted anterograde viral tracing, demonstrating a mainly contralateral cholinergic projection from the parabigeminal nucleus to dLGN. In addition, we saw a sparse ipsilateral projection from the rostral pedunculopontine tegmentum to dLGN and TRN. Next, we used a fluorescent reporter line (Ai9) to visualize cholinergic innervation in dLGN and TRN during early postnatal life. In dLGN, innervation began by the end of the first week, increased steadily with age, and reached an adult-like state by the end of the first month. Furthermore, using a model of visual deafferentation (math5-/-), we showed that the absence of retinal input resulted in disruptions in the trajectory, rate, and pattern of cholinergic innervation in dLGN. In TRN, innervation began during week 1 in the ventral non-visual sectors, proceeded into the dorsal visual sector during week 2, and reached adult-like levels by week 3. To assess the functional maturation of cholinergic synapses within TRN, we used a channelrhodopsin-2 reporter and selectively stimulated cholinergic afferents while conducting recordings from TRN neurons. Postsynaptic responses appeared in non-visual sectors of TRN during the first postnatal week, and in the visual sector by week 2. By the end of the first month, all sectors of TRN exhibited adult-like biphasic responses. Together, these studies shed light on the organizational pattern and developmental progression of cholinergic input to the visual thalamus.

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