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Title: Transgenic and optogenetic manipulation of inhibition in mouse visual thalamus
Author: Ye, Zhiwen
ISNI:       0000 0004 5922 683X
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2014
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This thesis examines GABAA receptor (GABAAR) and GABAB receptor (GABABR) mediated inhibition within the mouse dorsal lateral geniculate nucleus (dLGN) with a particular emphasis on the significance of GABA release from local interneurons. The removal of the gamma2 subunit from thalamic relay neurons of the dLGN in the HDC-gamma2 mouse strain was shown to reduce the overall sIPSC frequency across all relay neurons with an absence of IPSCs in a subset of Y-type thalamic relay neurons. The IPSCs associated with the remaining relay neurons exhibited slower rise-times and decays and were insensitive to diazepam, indicating the absence of the gamma2 subunit. Potentiation of these slower IPSCs by DMCM further suggested that the remaining IPSCs were mediated by gamma1 subunit-containing GABAA receptors. In contrast, removal of the GABAB1 subunit resulted in a complete loss of postsynaptic GABABR responses within the mouse dLGN in all cells so far examined. The baclofen-induced membrane hyperpolarization was lost from HDC-GABAB1 cells and elevated ambient GABA concentrations resulted in a significantly smaller membrane hyperpolarization. Although HDC-GABAB1 mice did not exhibit a major visual deficit in a novel object recognition task, local field potential recordings during the animals sleep period revealed a shift in the power spectrum towards 1-4 Hz delta band of oscillatory activity locally within the visual cortex. I also identified the Sox14 gene as a marker for dLGN interneurons. Channelrhodopsin-2 (ChR2) activation of Sox14 interneurons not only gave rise to time-locked phasic inhibition in the dLGN relay neurons, this stimulation also induced tonic inhibition in an activity-dependent manner, mediated by the activation of extrasynaptic delta-containing GABAARs. However, action potential induced GABA release from interneuron is not a conspicuous feature of simultaneous paired interneuron to relay neuron recordings.
Supervisor: Brickley, Stephen ; Wisden, William Sponsor: China Scholarship Council ; Department for Business ; Innovation and Skills ; Welcome Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available