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IBCS Seminar

Disrupted spatial coding in hippocampal and cortical circuits in mouse models of dementia Abstract

Dr Jon Brown Senior Lecturer Exeter University

Event details

Dementias, such as Alzheimer’s disease, are associated with severe spatial memory deficits which likely arise due to dysfunction in hippocampal and parahippocampal circuits. These circuits rely on precise encoding of spatial, directional and velocity information for spatially-sensitive neurons, such as place cells in the hippocampus and grid cells in the medial entorhinal cortex (mEC), to faithfully represent the environment.
In this seminar I will present some of our recent published and unpublished studies in which we have probed neural circuit dysfunction in mouse models of dementia-like pathology, using a range of in vitro and in vivo electrophysiological techniques. Specifically we have examined place, grid, head-direction and speed encoding in the rTg4510 mouse model of tau pathology. Alongside an analysis of neuronal network oscillations at a local field potential (LFP) level, taken together, the data I will present strongly suggest a profound deficit in locomotor speed encoding in the hippocampal formation.
Furthermore, I will also present evidence from a mouse model of amyloid pathology, a model of β-amyloid deposition, which also displays a context-specific deficit in locomotor speed encoding in the entorhinal cortex.
These deficits in locomotor speed encoding are likely to severely impact the ability of animals to continuously update positional information and thus will disrupt path integration systems. Ultimately, this is likely to result in substantial impairments to egocentric spatial processing, which, may contribute to the serious spatial memory processing deficits observed in clinical dementias.

Dr Jon Brown graduated from University of Manchester with a BSc and then an MRes in Neuroscience. Subsequently, he obtained a PhD from the University of Bristol (working Profs Ceri Davies and Graham Collingridge FRS), whilst based in the Neurology Centre of Excellence for Drug Discovery at GlaxoSmithKline. He went on to take up postdoctoral positions both at GSK and University of Bristol (working with Prof Andy Randall) before being appointed Senior Research Fellow and then Senior Lecturer at the University of Exeter Medical School.
He currently runs a research group which uses experimental neurophysiological approaches focussed on exploring how neuronal function is affected in neurological disease. His lab is funded by Alzheimer’s Research UK, Alzheimer’s Society, NC3Rs, MRC and BBSRC as well as pharmaceutical companies such as Eli Lilly and Janssen.

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