Functional contribution of L-type calcium channels to basolateral amygdala excitability and pathophysiology
department or school: Medicine, Faculty of
data provider: DSpace
degree campus: UBCV
creator: Zhang, Yiming
issued: 2021-01-04T18:13:49Z
issued: 2020
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: Calcium influx via neuronal L-type calcium channels (LTCCs) has been implicated in regulating activity-dependent gene transcription, synaptic plasticity, and synaptogenesis. While gain-of-function mutations in neuronal LTCCs have been linked to neurodevelopmental diseases, including autism spectrum disorders (ASDs), the role of LTCCs in regulating neuronal electrophysiological properties during early development remains unclear. The amygdala complex contributes toward emotional processes such as fear, anxiety and social cognition and studies suggest that increased excitability of basolateral amygdala (BLA) principal neurons underlie certain neuropsychiatric disorders. While LTCCs are expressed throughout the BLA, direct evidence for increased LTCC activity affecting BLA excitability and potentially contributing to disease pathophysiology is lacking. In Chapter Ⅰ of my study I investigated the contributions of LTCCs to the excitability and synaptic activity of BLA principal neurons at early developmental stages (postnatal day 7 (P7) and P21). By directly applying LTCC agonist (S)-Bay K8644 (BayK) onto brain slices, I found that BLA principal neurons displayed distinct alterations between P7 and P21 in intrinsic excitability properties, including firing frequency response, spike-frequency adaptation and altered spontaneous neurotransmission. These results suggested the possibility that the functional increase of LTCC activity at different stages of neurodevelopment may lead to alterations to BLA neuronal network activity. To investigate the effects of increased LTCC activity as it might relate to the underlying mechanism of developmental disorders such as ASD, in Chapter Ⅱ I examined the effects of increased LTCC function in early development on long-lasting neuronal excitability, synaptic plasticity and behavioral phenotypes. Bilateral injection of BayK into the BLA at different early stages (P7 or P14) followed by recovery and testing at P28 showed enhanced BLA neur…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/76928
note: FUNCTIONAL CONTRIBUTIONS OF L-TYPE CALCIUM CHANNELS TO BASOLATERAL AMYGDALA EXCITABILITY AND PATHOPHYSIOLOGY by Yiming Zhang B.Sc., Henan Agricultural University, China, 2009 M.Sc., Soochow University, China, 2012 A DISSERTATION SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in The Faculty of Graduate and Postdoctoral Studies (Neuroscience) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) December 2020 © Yiming Zhang, 2020 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled: Functional contributions of L-type calcium channels to basolateral amgydala excitability and pathophysiology Submitted by Yiming Zhang in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Neuroscience Examining Committee: Terrance P. Snutch, Neuroscience, UBC Supervisor Brian MacVicar, Neuroscience, UBC Supervisory Committee Member Anthony Phillips, Psychiatry, UBC University Examiner Filip Van Petegem, Biochemistry, UBC University Examiner Additional Supervisory Committee Memmbers: Shernaz Bamji, Cellular and Physiological Sciences, UBC Supervisory Committee Member Yu-Tian Wang, Neurology, UBC Supervisory Committee Member iii Abstract Calcium influx via neuronal L-type calcium channels (LTCCs) has been implicated in regulating activity-dependent gene transcription, synaptic plasticity, and synaptogenesis. While gain-of-function mutations in neuronal LTCCs have been linked to neurodevelopmental diseases, including autism spectrum disorders (ASDs), the role of LTCCs in regulating neuronal electrophysiological properties during early development remains unclear. The amygdala complex contributes toward emotional processes such as fear, anxiety and social cognition and studies suggest that increased excitability of basolateral amygdala (BLA) principal neurons underlie certain neuropsychiatric disorders. While LTCC…
has type: Thesis/Dissertation
date issued: 2021-05
is shown at: 10.14288/1.0395439
language: eng
degree discipline: Neuroscience
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/76928