This thesis describes the developmental expression and anatomical distribution of Copine-6, a neuron specific member of the Copine family of calcium-dependent phospholipid-binding proteins, in rodent brain. A polyclonal antibody targeting the full Copine-6 sequence has been characterised prior to its employment for the immunohistochemical analysis of rodent embryonic and adult brain tissue. Several different Copine-6 labelled neuron populations in the neocortex, hippocampus and olfactory bulbs were discovered, and one of these with an unusual ‘spiny’ morphology in the adult rodent corpus callosum, bordering the neurogenic subventricular zone and rostral migratory stream, was studied in detail. A full molecular characterisation of these Copine-6 ‘spiny’ neurons showed that these cells are mature, GABAergic, axonless interneurons with putative synaptic communication, unusual for their location in the white matter close to the region of adult neurogenesis. A full bromodeoxyuridine (BrdU) birth-dating analysis was performed, which indicated an early embryonic birthdate for the Copine-6 spiny cells. This timeframe is typical of cortical GABAergic interneurons suggesting that their unusual positioning is programmed from embryogenesis. Furthermore, electron microscopic analysis of these Copine-6 interneurons in Chapter 5 confirms that indeed these cells contain vesicles and are synaptically integrated as postsynaptic recipients. The presence of vesicles in the architecturally dendritic processes is suggestive of dendro-dendritic signalling by these cells. Observations from electron microscopic nanoparticle labelling also showed that the Copine-6 protein is restricted to the plasma membrane, smooth endoplasmic reticulum, and multi-vesicular bodies. These embryonically generated Copine-6 labelled axonless interneurons are a novel neuron population in the corpus callosum, and the presence of vesicles in the dendritic processes of these cells suggests that they might have a novel communication mechanism.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:627778 |
| Date | January 2013 |
| Creators | Faram, Ruth Helen |
| Contributors | McIlhinney, R. A. Jeff |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://ora.ox.ac.uk/objects/uuid:0af499ea-1a02-4ab8-9b88-bc5526b67421 |
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