Neurodegenerative Disease

A major research focus in the lab at the moment is on understanding what happens to brain circuits (and specifically, hippocampal and neocortical circuits) during neurodegenerative disorders such as Alzheimer's Disease. We are utilising and developing a number of platform technologies to this end, including tools to image the activity of populations of neurons in the neocortex and hippocampus while an animal is performing a spatial memory task, tools to perform targeted whole-cell patch-clamp electrophysiological recording from specific cell types, and advanced tools for analysis of the datasets thus obtained. We are applying these tools to characterise both amyloid and tau based mouse models of Alzheimer’s Disease, as well as using them to better understand the effect that proposed therapies have on restoration of information processing in hippocampal-neocortical circuits.

Optical Neurotechnology

The use of light to probe and manipulate brain tissue is one of the core experimental activities in the lab. Ongoing projects include: the two-photon targeted robotic patch clamp, a platform for imaging calcium signals in populations of neurons in the hippocampus during performance of memory tasks, a platform for mapping cortical circuits using two photon temporally focused multifocal imaging and genetically encoded voltage indicators.
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Left: A video frame taken while imaging neural activity in hippocampal region CA1 of an awake mouse performing a spatial exploration task. The region of tissue was virally transfected with GCaMP6-mRuby; mRuby allows us to visualise cell structure and location in red, with GCaMP6 showing green flashes of activity around the membrane.
Information Theoretic Tools for Studying Cortical Circuit Function

New optical tools for probing neural circuit functionality require the development of new signal processing and data analysis algorithms. On the signal processing end, we have developed advanced image segmentation algorithms capable of automatically pulling out regions of interest from calcium imaging movies, and a calcium transient detection framework based on Finite Rate of Innovation theory, which performs extremely well. To analyse the resulting data, we continue to work on information theoretic algorithms for studying multivariate time series, and in particular tools for dissecting out distinct statistical components of the neural code, as well as dimensionality reduction approaches necessary to deal with large-scale neural recording technology.

Neural Coding

We have worked extensively on neural coding of sensory information, in systems ranging from the visual and somatosensory cortices, to the lateral geniculate nucleus of the thalamus, to the cerebellum. Current work focuses on quantifying encoding and retrieval of spatial information in the hippocampus., and on information processing by ON and OFF pathways in the mouse dorsal LGN.
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