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Optogenetic investigation of neuronal excitability and sensory-motor function following a transient global ischemia in mice

University of British Columbia

Global ischemia occurs during cardiac arrest and has been implicated as a complication that can occur during cardiac surgery. It induces delayed neuronal death in human and animal models, particularly in the hippocampus, while it also can affect the cortex. Other than morphology and measures of cell death, relatively few studies have examined neuronal networks and motor-sensory function following reversible global ischemia in vivo. Optogenetics allows the combination of genetics and optics to control or monitor cells in living tissues. Here, I adapted optogenetics to examine neuronal excitability and motor function in the mouse cortex following a transient global ischemia. Following optogenetic stimulation, I recorded electrical signals from direct stimulation to targeted neuronal populations before and after a 5 min transient global ischemia. I found that both excitatory and inhibitory neuronal network in the somatosensory cortex exhibited prolonged suppression of synaptic transmission despite reperfusion, while the excitability and morphology of neurons recovered rapidly and more completely. Next, I adapted optogenetic motor mapping to investigate the changes of motor processing, and compared to the changes of sensory processing following the transient global ischemia. I found that both sensory and motor processing showed prolonged impairments despite of the recovery of neuronal excitability following reperfusion, presumably due to the unrestored synaptic transmission. Interestingly, motor processing recovered faster and more completely than sensory processing. My results suggest a uniform suppression of synaptic transmission, both in excitatory and inhibitory network, despite the rapid recovery of neuronal excitability and morphology, following a global ischemia and reperfusion. This prolonged suppression of synaptic transmission might impede the recovery of sensory and motor processing with differential severity. Besides, I extended tools for mesoscopic imaging using novel optogenetic sensors, including genetically encoded Ca2+ indicators - GCaMPs, and extracellular glutamate sensor - iGluSnFR. I found that iGluSnFR has fastest kinetics for reporting both sensory and spontaneous activity in the cortex, which can resolve temporal features of sensory processing that were not readily observed with GECIs. I suggest that iGluSnFR tools have potential utility in normal physiology, and neurologic pathologies in which abnormalities in glutamatergic signaling are implicated, such as stroke.

Text

2015-12-19

Attribution-NonCommercial-NoDerivs 2.5 Canada

http://hdl.handle.net/2429/55954

Neuroscience

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/2.5/ca/