Description
- Abstract:
- Most sensory information destined for the neocortex is relayed there from the thalamus, where considerable transformation occurs. One powerful means of transformation involves interactions between thalamocortical neurons that carry information to cortex and inhibitory neurons of the thalamic reticular nucleus (TRN) that regulate the flow of those data. In this dissertation, I address two topics. First, I describe a novel organizational and operational framework for somatosensory circuits in the mouse TRN. I show that there are two groups of genetically defined TRN neurons that are topographically segregated, physiologically distinct, and innervated by independent thalamic nuclei. My results suggest that these two structurally and functionally distinct cell types make discrete subcircuits in somatosensory TRN. Functionally, the two subcircuits have different properties determined by the two neurons’ intrinsic physiology and the short-term dynamics of their thalamic input synapses. My results suggest that the inhibitory output of each TRN subcircuit appears to be tuned to the temporal characteristics of the signals it preferentially processes. Second, I address how deletion of the Tsc1 gene in thalamocortical neurons affects the structure and function of thalamic circuits. Tsc1 is a regulator of the mTOR signaling pathway and mutations of the gene in humans can cause a neurodevelopmental disorder, Tuberous Sclerosis Complex. I found that selective Tsc1 deletions in thalamic relay neurons of mice affected the cells’ size, dendritic complexity, and membrane and spike-firing properties, and I characterized the biophysical properties of some of key membrane ion currents. I then determine how Tsc1 deletion in relay neurons affects the function of synapses in the thalamus-to-TRN circuit. Finally, I discovered that Tsc1 deletions induced ectopic electrical synapses between relay neurons in the thalamus. Normally, thalamic relay neurons do not express electrical synapses after early postnatal development. Here, I found that electrical synapses in Tsc1-mutated neurons are present and persist through adulthood. I characterized the properties of these ectopic electrical synapses and their influence on thalamic activity. The results of my thesis provide insights on the functions of thalamic circuits and how a genetic deletion observed in a neurodevelopmental disorder impacts neuronal and synaptic structure and function.
- Notes:
- Thesis (Ph. D.)--Brown University, 2019
Access Conditions
- Rights
- In Copyright
- Restrictions on Use
- All rights reserved. Collection is open to the Brown community for research.
Citation
Martinez-Garcia, Rosa I.,
"Functions and genetically induced dysfunctions of neural circuits in the thalamus"
(2019).
Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://doi.org/10.26300/661t-m253
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Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations
Theses and Dissertations for the Molecular Biology, Cell Biology, and Biochemistry department....