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The neurofilament triplet protein and other neurochemical markers in rat neocortex


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Kirkcaldie, Matthew 2001 , 'The neurofilament triplet protein and other neurochemical markers in rat neocortex', PhD thesis, University of Tasmania.

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Evidence for intrinsic modularity in the mammalian neocortex is difficult to reconcile in a
single coherent scheme of organisation. Instead, it appears that certain characteristics of
neuronal morphology and interconnection produce a cortex with an intrinsic columnar
bias, formed and regionally differentiated under the influence of subcortical afferents, and
that the cortex as a whole is more homogeneous than may have been expected. Against
this background, a growing set of characteristic biochemical markers expressed by
individual neurons has emerged as an important prospect for recognising the mix of
neuronal subgroups in individual regions, and several studies have made progress in
associating these "chemical phenotypes" with the morphologies, connectional
preferences, distributions and electrophysiological qualities of the neurons exhibiting
them. Most chemical phenotypes are expressed by subgroups of GABAergic neurons.
Immunohistochemical labelling of the neurofilament triplet (NF) intermediate
filament proteins allows subpopulations of the largest neuronal group, the pyramidal
cells, to be identified throughout the brain. Characterisation of the properties associated
with cellular expression of NFs would permit phenotypic groupings of most cortical
neurons, enabling the evaluation of neuronal populations in wide regions of the brain
using simple techniques. This thesis comprises studies of NF-associated properties in the
context of several key chemical phenotypes.
The overall distribution of immunolabelling produced by SMI32, an antibody
recognising perikaryal neurofilament, was examined and characterised in the rat cortex.
Retrograde tracing studies evaluated the possibility that the presence of NF enables
longer projections in corticocortical neurons. Ultrastructural examination of cortical
axons was used to examine the relationship between axonal neurofilaments, myelination
and axon calibre in the rat cortex. The developmental emergence of SMI32 labelling was
examined, and comparisons with the appearance of key GABAergic phenotypes was used
to correlate NF expression with the changing environment of developing cortex. Finally,
the usefulness of cultured embryonic rat neurons for studying the development and
intracellular distribution of NFs and GABAergic phenotypes was examined using several
timepoints during a three week development in vitro. SMI32-labelled NFs were found in around 10% of neurons in several regions;
characteristic laminar patterns of labelling were observed in the cortex as a whole,
consistently appearing in particular cortical areas. SMI32 labelling in retrogradely
labelled cells was found not to correlate with estimates of the projection distances
involved, although some evidence for regionally specific differences in NF proportions of
projection neurons was observed. Presumed NFs in cortical axons of the corpus callosum
exhibited a strong correlation with axon calibre and myelination, while differences
observed in regional NF distribution were found to correlate with obvious ultrastructural
differences in the cortex. The emergence of SMI32 labelling correlated with changes in
the expression of other chemical markers in vivo, whereas the environmental differences
of in vitro culture produced significant alterations in the observable chemical phenotypes,
notably the early absence of NFs recognised by the SMI32 antibody.
The role played by neurofilaments in the cells which express them remains
mysterious, but it is clear that there are major variations in their regional and intracellular
expression and modification. They remain a strong prospect for subtyping pyramidal
cells, since they are probably expressed by neurons whose axons are myelinated.

Item Type: Thesis - PhD
Authors/Creators:Kirkcaldie, Matthew
Keywords: Neurochemistry, Neurophysiology, Neurons, Neocortex
Copyright Holders: The Author
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Copyright 2001 the Author - The University is continuing to endeavour to trace the copyright
owner(s) and in the meantime this item has been reproduced here in good faith. We
would be pleased to hear from the copyright owner(s).

Additional Information:

Thesis (Ph.D.)--University of Tasmania, 2001. Includes bibliographical references

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