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Title: Medial prefrontal cortex synaptic connectivity in disrupted-in-schizophrenia-1 mouse models
Author: Kurihara, Mai
ISNI:       0000 0004 5914 6637
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2015
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Neuropsychiatric disorders arise from a combination of genetic susceptibilities and environmental factors. Disrupted cognitive functions are often observed in these illnesses and despite many years of research, are still poorly understood. Disrupted-in-Schizophrenia-l (DISC1) is a gene implicated in the susceptibility to mental illnesses. The work presented here examines the prelimbic cortex (PrL), an area linked with cognitive processes, in both its local connectivity and interaction with the hippocampus, HPC (long-range connectivity). The first results chapter studies the neuronal diversity in the deep layers of the PrL of C57Blf6 mice. Three neuronal subtypes were identified based on neuronal excitability patterns: Regular spiking, intrinsically bursting and fast-spiking putative interneurons. Investigations of regular spiking neurons in the DISC1-Q31L and -Ll00P exon 2 point mutation models showed no changes in the PrL local and long-range connectivity. On the other hand, regular spiking neurons in the BAC-DISCl truncated mouse model, overexpressing a truncated form of DISC1, had altered frequency of spontaneous postsynaptic currents, changes in inhibitory decay and increased short-term facilitation in the HPC-PrL pathway at 10 Hz stimulation frequency. Furthermore, studies in vivo demonstrated altered coherence in the gamma frequency band between the dorsal HPC and ventral HPC during wake/sleep states and between the ventral HPC and PrL during performance of an anxiety-related task. These findings provide novel insights into the effect of mutant DISCl on the PrL local and long-range connectivity, its implications in neuropsychiatric disorders and normal function of the PrL and HPC-PrL pathway.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available