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WIN Wednesday Works In Progress

Pre-clinical imaging of a rare variant transgenic rodent model for schizophrenia

Speaker: Jeffery Stedehouder

Abstract: Schizophrenia is a major debilitating psychiatric disorder for which the underlying neurobiology has remained elusive. Recent years have seen the identification of various rare, single-gene protein-truncating variants (frequency < 0.1%) which convey high risk for the disease (odds ratios 3-60). In an attempt for unbiased unraveling of schizophrenia neurobiology, we are currently performing large-scale in vivo electrophysiological recordings using multiple, simultaneous Neuropixel probes across rodents containing such a rare transgenic variant.

Here, as a translational pilot study, I propose to perform a preclinical rodent 7T imaging study of an independent cohort of these rare variant transgenic mice. I plan to perform a single time-point, structural and functional imaging (structural MRI, diffusion MRI, rs-fMRI) approach in a sufficiently powered, matched adult group of transgenic mice of both sexes as well as littermate control mice. The first aim would be to examine differences between transgenic mice and littermate controls in any imaging modality. The second aim would be to examine whether regional correlations can be observed between large-scale in vivo electrophysiological approaches (from parallel experiments) and imaging modalities in either transgenic and/or wildtype mice.

Together, large-scale in vivo electrophysiology (single-cell, single action potential resolution) and pre-clinical imaging (translational power) in our transgenic mouse lines could present a particularly powerful combination to start elucidating schizophrenia pathophysiology.




WIN-MRS event - Functional Magnetic Resonance Spectroscopy: a dynamic read out of Glutamate and GABA?

Speaker: Helen Barron

Abstract: Proton-Magnetic Resonance Spectroscopy (MRS) is a non-invasive brain imaging technique used to measure the concentration of different neurochemicals. MRS data is typically acquired across several minutes, before individual transients are averaged through time to give a measurement of neurochemical concentrations. However, this approach is not sensitive to more rapid temporal dynamics of neurochemicals, including those that reflect functional changes in neural computation relevant to perception, cognition, motor control and ultimately behaviour. In this talk I will show how functional MRS (fMRS) can be used to obtain event-related measures of neurochemicals. Event-related fMRS involves presenting different experimental conditions as a series of trials that are intermixed. Critically, this approach allows spectra to be acquired at a time resolution in the order of seconds. I will first show how we can use this approach to characterise the shape of the glutamate response function in primary visual cortex, in response to visual stimulation. I will then show how recall of a visual cue from a paired associate is accompanied by a transient increase in the ratio between glutamate and GABA in visual cortex, where these excitatory-inhibitory fluctuations are predicted by activity in the hippocampus. These data show how event-related fMRS can be used to measure dynamic changes in neurochemicals at a temporal resolution relevant to computations that support human cognition and behaviour.