Title:
|
Medial prefrontal cortex synaptic connectivity in disrupted-in-schizophrenia-1 mouse models
|
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.
|