Muscarinic Cholinergic Modulation of Neuronal Excitability and Dynamics via Ether-a-go-go-Related Gene Potassium Channel in Rodent Neocortical Pyramidal Cells
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Case Western Reserve University School of Graduate Studies / OhioLINK
2019
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=case1559904265174505 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-case15599042651745052021-08-03T07:11:21Z Muscarinic Cholinergic Modulation of Neuronal Excitability and Dynamics via Ether-a-go-go-Related Gene Potassium Channel in Rodent Neocortical Pyramidal Cells Cui, DongBo Neurosciences Neurobiology Biology Biophysics Ether-a-go-go-Related Gene Potassium Channel ERG Neocortex Pyramidal Cells Neuronal Excitability Persistent Activity Muscarinic Cholinergic Receptors Spike Frequency Adaptation SFA Signal Correlation Working Memory Schizophrenia Acetylcholine (ACh) is a neurotransmitter well-known to play essential roles in modulating sensory and higher cognitive functions. The basal forebrain is a major source of ACh to the neocortex and its activity is heightened during cognitive processes. Activation of muscarinic acetylcholine receptors (mAChR) has several functional consequences in the neocortex. At the behavioral level, it is required for attention maintenance and working memory. At the circuit level, it facilitates long term potentiation and enhances the coding capacity of a population of neurons. At the cellular level, it increases neuronal excitability by modulating a constellation of ionic currents. It also allows the cell to maintain its activity beyond the stimulus, a phenomenon termed “persistent activity”, which is often seen as the cellular hallmark of working memory. In spite of the extensive observations made with respect to mAChR activation at different levels, the cellular mechanisms of these phenomena are not well understood. In this work, I used electrophysiological, optogenetic, and imaging methods to investigate the cellular basis of various phenomena of mAChR activation.In the first part of my results, I investigated the ionic mechanism of persistent activity triggered by depolarizing stimuli following mAChR activation, and found that Ether-a-Go-Go Related Gene (ERG) Potassium channel was down-modulated post-stimuli, which, in turn, depolarized the cell and increased neuronal excitability. ERG blockers abolished persistent firing in temporal and prefrontal association cortices. Next, I investigated what ionic current was responsible for the increase in excitability upon mAChR activation. With optogenetic tools, I stimulated cholinergic fibers originating from the basal forebrain in the neocortex, and found that mAChR activation increased neuronal excitability during the stimulus by down-modulating a component of spike frequency adaptation (SFA) mediated by ERG. I found that SFA reduced by mAChR activation is responsible for the decrease in inter-neuronal correlative activity previously observed in vivo. Thus, a variety of neurodynamic phenomena of mAChR activation can be traced back to its modulation of the biophysical properties of neurons. 2019-08-26 English text Case Western Reserve University School of Graduate Studies / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=case1559904265174505 http://rave.ohiolink.edu/etdc/view?acc_num=case1559904265174505 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
| collection |
NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Neurosciences Neurobiology Biology Biophysics Ether-a-go-go-Related Gene Potassium Channel ERG Neocortex Pyramidal Cells Neuronal Excitability Persistent Activity Muscarinic Cholinergic Receptors Spike Frequency Adaptation SFA Signal Correlation Working Memory Schizophrenia |
| spellingShingle |
Neurosciences Neurobiology Biology Biophysics Ether-a-go-go-Related Gene Potassium Channel ERG Neocortex Pyramidal Cells Neuronal Excitability Persistent Activity Muscarinic Cholinergic Receptors Spike Frequency Adaptation SFA Signal Correlation Working Memory Schizophrenia Cui, DongBo Muscarinic Cholinergic Modulation of Neuronal Excitability and Dynamics via Ether-a-go-go-Related Gene Potassium Channel in Rodent Neocortical Pyramidal Cells |
| author |
Cui, DongBo |
| author_facet |
Cui, DongBo |
| author_sort |
Cui, DongBo |
| title |
Muscarinic Cholinergic Modulation of Neuronal Excitability and Dynamics via Ether-a-go-go-Related Gene Potassium Channel in Rodent Neocortical Pyramidal Cells |
| title_short |
Muscarinic Cholinergic Modulation of Neuronal Excitability and Dynamics via Ether-a-go-go-Related Gene Potassium Channel in Rodent Neocortical Pyramidal Cells |
| title_full |
Muscarinic Cholinergic Modulation of Neuronal Excitability and Dynamics via Ether-a-go-go-Related Gene Potassium Channel in Rodent Neocortical Pyramidal Cells |
| title_fullStr |
Muscarinic Cholinergic Modulation of Neuronal Excitability and Dynamics via Ether-a-go-go-Related Gene Potassium Channel in Rodent Neocortical Pyramidal Cells |
| title_full_unstemmed |
Muscarinic Cholinergic Modulation of Neuronal Excitability and Dynamics via Ether-a-go-go-Related Gene Potassium Channel in Rodent Neocortical Pyramidal Cells |
| title_sort |
muscarinic cholinergic modulation of neuronal excitability and dynamics via ether-a-go-go-related gene potassium channel in rodent neocortical pyramidal cells |
| publisher |
Case Western Reserve University School of Graduate Studies / OhioLINK |
| publishDate |
2019 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=case1559904265174505 |
| work_keys_str_mv |
AT cuidongbo muscariniccholinergicmodulationofneuronalexcitabilityanddynamicsviaetheragogorelatedgenepotassiumchannelinrodentneocorticalpyramidalcells |
| _version_ |
1719455586977841152 |