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Dissertation
Thalamic inputs differently regulate the adolescent development of excitatory and inhibitory neurons in the mPFC
Doctor of Philosophy (Ph.D.), Drexel University
Aug 2021
DOI:
https://doi.org/10.17918/00000860
Abstract
GABAergic interneurons (INs) are essential for the performance of prefrontal cortex (PFC)-dependent complex behaviors which are found abnormal in neurodevelopmental and psychiatric disorders. However, what triggers the abrupted activity of GABAergic INs during critical adolescent development is unknown. The present study downregulated the activity of the mediodorsal thalamus (MD), a major upstream regulatory center of the mPFC, during adolescence and investigated its function in controlling the development of prefrontal somatostatin (SST)- and parvalbumin (PV)-INs. We found that MD inhibition in adolescence increased the MD excitability in adults and induced compensatory downregulation of the excitatory neurons in the PFC. Our results also showed an increase in E/I ratio shortly after MD inhibition, and this change is attributable to the weakened inhibitory transmission mediated by GABAergic INs. Importantly, MD inhibition in adolescence facilitated the developmental increase of membrane excitability and decrease of synaptic NMDAR components in SST-INs, promoting their maturation during adolescence. In contrast, MD inhibition induced relatively mild changes in PV-INs, including a delayed and transient increase in cell excitability and a decreased AMPAR- but not NMDAR- mediated currents, as well as long-lasting short-term plasticity. For the first time, this study shows that inhibiting MD activity in adolescence could induce more numerous changes on the developmental trajectories of SST-INs than PV-INs, although the latter widely-reported more sensitive during adolescence in the mPFC. This finding provides novel insights into a fundamental question of how the MD afferents differentially regulate the development of prefrontal GABAergic signaling involved in the two major subtypes of INs, emphasizing the importance of SST-INs in prefrontal function related to neurodevelopmental disorders.
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Details
- Title
- Thalamic inputs differently regulate the adolescent development of excitatory and inhibitory neurons in the mPFC
- Creators
- Shasha Yang
- Contributors
- Wen-Jun Gao (Advisor)Kimberly J. Dougherty (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xi, 132 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- College of Medicine; Neurology; Drexel University
- Other Identifier
- 991015473892204721