M1SYNC · Circuit mechanisms underlying dynamic spike time synchronization in mouse motor cortex

Circuit mechanisms underlying dynamic spike time synchronization in mouse motor cortex

The scientific objective of the CIG project was to determine the mechanisms underlying network oscillations in mouse motor cortex, and how this rhythmic activity gates the integration of whisker-evoked sensory inputs within sensorimotor circuits. Understanding the mechanisms and functions of motor cortex oscillations is clinically important, as these brain rhythms are disturbed in multiple brain disorders, including the enhanced beta-frequency oscillations associated with the loss of voluntary movement in Parkinson’s Disease, the acceleration of high-frequency oscillations that can occur at the onset of motor seizures, and the global breakdown of sleep-related slow wave oscillations in Alzheimer’s Disease. Interpreting sensory evidence from a moving sensory organ requires a combination of both sensory and motor information. The initial results suggested that activation of vibrissal motor cortex could synchronize slow activity across sensorimotor networks, and enable a phase-to-rate transformation for spike encoding of subsequent whisker contacts. To dissect the underlying circuitry, it was necessary to establish the state-of-the-art methodologies for cell type-specific ChR2 expression, multielectrode array recordings and whole-cell patch-clamp techniques, both in acute brain slices in vitro and anesthetized mice in vivo. The successful application of these techniques enabled the group to demonstrate that motor cortex modulates whisker-evoked responses via cortifugal projections from layer V and VI to sensory thalamus. This data has been disseminated at national and international neuroscience meetings, and is currently being written up for publication after the finalization of the CIG project. The CIG funding was critical for establishing and supporting these methodologies in Dr Mann’s laboratory, and attracting students from the Wellcome Trust-funded OXION and Neuroscience courses to undertake the experimental work. Overall, this involved training 7 European students in the techniques for in vitro and/or in vivo electrophysiology (from Germany, Switzerland, Austria, Netherlands, Republic of Ireland, Denmark and England). During the CIG project, Dr Mann also contributed to knowledge transfer by providing seminar and practical demonstrations on electrophysiological techniques for students on the Wellcome Trust-funded OXION and Neuroscience courses, and on multielectrode recordings at the Plymouth Microelectrode workshop (http://www.mba.ac.uk/microelectrode-techniques-for-cell-physiology/). Dr Mann received the CIG award following his appointment as an Associate Professor of Neuroscience at the Department of Physiology, Anatomy & Genetics, University of Oxford, in association with a Tutorial Fellowship in Medicine & Biomedical Sciences at St Hugh’s College, Oxford. This position involves providing undergraduate lectures and tutorials, in addition to establishing a research group. The CIG award has been a key step for Dr Mann to secure further research funding from the BBSRC and MRC, expand his research group (currently 8 researchers), and integrate with the Departmental and University research community.

Data: CORDIS, © European Union