Numerous human central nervous system disorders, particularly those involving higher cognitive functions, are poorly understood. The use of rodent models of such disorders has greatly advanced knowledge of the pathophysiological mechanisms underlying these diseases, but many questions remain unanswered. The present study examines the neurophysiology of neurons in the hippocampal formation in transgenic mouse models of two human CNS disorders, namely Alzheimer's disease and schizophrenia. The rTg4S1 0 mouse model over-expresses a mutant form of the microtubule associated protein tau, a protein involved in the formation of neurofibrillary tangles, which are a major pathological hallmark of Alzheimer's disease and a number of other dementi as collectively known as tauopathies. Profound age-dependent alterations in the intrinsic and synaptic properties of hippocampal CAl pyramidal neurons were observed in rTg4Sl0 mice. These mice also displayed alterations in the intrinsic properties of stellate neurons in layer IIIIII of the medial entorhinal c0l1ex. Both the hippocampus and the entorhinal c0l1ex are intimately involved in memory functions, so these results point to potential cellular correlates for the memory deficits observed in rTg4S1 0 mice, and may have implications for the memory impairments in Alzheimer's disease and other tauopathies. The DISCl mouse model expresses a truncated form of the Disrupted-in Schizophrenia- l gene, which has been implicated in psychiatric illnesses including schizophrenia. In DISCl mice, only subtle changes in the intrinsic properties of hippocampal CAl pyramidal neurons were observed, but distinct alterations in plasticity of synaptic transmission onto these neurons were revealed. These findings may have implications for the working memory deficits observed in schizophrenia.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:681563 |
| Date | January 2013 |
| Creators | Booth, Clair |
| Publisher | University of Bristol |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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