Applying optogenetic techniques to study the microcircuitry of the subthalamic nucleus

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dc.contributor.advisor Freestone, P en
dc.contributor.advisor Lipski, J en
dc.contributor.advisor Trew, M en Lui, Si Yin en 2019-07-21T22:00:15Z en 2019 en
dc.identifier.uri en
dc.description Full Text is available to authenticated members of The University of Auckland only. en
dc.description.abstract The subthalamic nucleus (STN) is the only glutamatergic nucleus in the basal ganglia, receiving input from multiple brain regions, but most importantly from the cortex. This cortical innervation is of particular interest because a brief cortical input transforms into a prolonged and amplified STN output. This “reverberating” effect suggests there is a local microcircuitry among STN neurons within the STN. Previous studies have alluded to this, but there has yet to be a combination of anatomical and functional evidence to explicitly prove synapses occur between STN neurons. The aim of our study is to investigate the microcircuitry in the STN. The optogenetic technique of channelrhodopsin-assisted circuit mapping (CRACM) was achieved by photostimulating channelrhodopsin-2 (ChR2)-expressing mouse brain slices in a grid pattern and monitoring electrophysiological current responses (“events”) in the recorded neurons. An event detection algorithm analysed the data in a high throughput manner to detect potential synaptic connections as “events clusters”. CRACM detected event clusters representing connections between STN neurons and application of glutamate receptor blockers confirmed that these events were mediated by a mixture of AMPA/kainate and NMDA glutamatergic receptors. Through pharmacological investigation, imaging and varying LED intensities, event clusters were verified to be presynaptic somas in the STN. The 2D spatial information that CRACM provided alluded to a rostromedial-to-caudolateral directionality in synaptic transmission between distal regions of the STN. Our findings provide the first direct evidence for a microcircuit of neurons within the STN, possibly providing the framework for the “reverberating” function. We also suggest a mechanism for the integration and processing of the various input the STN receives. en
dc.publisher ResearchSpace@Auckland en
dc.relation.ispartof Masters Thesis - University of Auckland en
dc.relation.isreferencedby UoA99265166313902091 en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri en
dc.title Applying optogenetic techniques to study the microcircuitry of the subthalamic nucleus en
dc.type Thesis en Biomedical Science en The University of Auckland en Masters en
dc.rights.holder Copyright: The author en
pubs.elements-id 776999 en Medical and Health Sciences en Medical Sciences en Physiology Division en
pubs.record-created-at-source-date 2019-07-22 en

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