Role of zincergic neurons in cortical function and plasticity

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dc.contributor.advisorDyck, Richard H.
dc.contributor.authorBrown, Craig E.
dc.date.accessioned2005-08-16T17:37:58Z
dc.date.available2005-08-16T17:37:58Z
dc.date.issued2004
dc.descriptionBibliography: p. 155-184en
dc.description.abstractZinc ions are essential for life as they regulate the function of numerous structural, transcriptional and enzymatic proteins. In addition to its role in basic cellular functioning, zinc is contained within and released from the nerve terminals of a subset of glutamatergic neurons in the central nervous system. Physiological studies have shown that synaptically-released zinc can powerfully modulate synaptic transmission by regulating the activation of numerous voltage and ligand gated ion channels and intracellular signaling proteins. Consequently, the goal of this thesis was elucidate the anatomical organization and functional significance of zinc-releasing (ie. zincergic) neurons in the mammalian forebrain, particularly within the cerebral cortex. To do this, we first describe a novel procedure for staining the cell bodies of zincergic neurons that eliminates background staining of zinc within synaptic terminals, thereby enabling a clear and accurate description of these neurons. Using this method, we found that zincergic neurons were typically pyramidal in shape and densely populated telencephalic structures such as the cerebral cortex, hippocampus and amygdala. In addition, labeled neurons were found in the lateral ventricle, lateral septum, zona incerta, as well as select regions of the hypothalamus, a region previously thought to be devoid of neurons with a zincergic phenotype. In order to implicate zincergic neurons in cerebral cortical plasticity, we characterized zincergic innervation of the mouse barrel cortex, our model system. Utilizing a zinc-specific retrograde labeling method, we found that the majority of zincergic projections to the barrel cortex originated from ipsilateral and callosal neurons situated within layers 2/3 and 6 of the cerebral cortex. Given that zinc is potent modulator of synaptic transmission, and that intracortical circuits drive experience-dependent reorganizations in the adult cortex, we then examined the effect of tactile stimulation or deprivation on the homeostatic regulation of zinc within barrel cortex synapses. Our data indicate that levels of synaptic zinc in layer 4 were rapidly and bi-directionally regulated by tactile experience. Furthermore, we found that the experience-dependent regulation of synaptic zinc was highly dependent on age, with aged animals no longer showing this capability. In summary, these results suggest that zincergic circuits comprise a chemospecific associative network that reciprocally interconnects telencephalic structures. Furthermore, our data implicate zincergic circuits in rapid, experience-dependent plasticity in the adult cerebral cortex, as well decrements in this plasticity that accompany senescence.en
dc.format.extentxiv, 184 leaves ; 30 cm.en
dc.identifier.citationBrown, C. E. (2004). Role of zincergic neurons in cortical function and plasticity (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/24443en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/24443
dc.identifier.isbn0494038543en
dc.identifier.lccAC1 .T484 2004 B765en
dc.identifier.urihttp://hdl.handle.net/1880/42200
dc.language.isoeng
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.titleRole of zincergic neurons in cortical function and plasticity
dc.typedoctoral thesis
thesis.degree.disciplinePsychology
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
ucalgary.item.requestcopytrue
ucalgary.thesis.accessionTheses Collection 58.002:Box 1492 520492009
ucalgary.thesis.notesUARCen
ucalgary.thesis.uarcreleaseyen
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