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Tom Mrsic-Flogel"Mapping synaptic connectivity between functionally characterised neurons in the neocortex"

Abstract :

Neuronal connectivity is fundamental to information processing in the brain.
Understanding the mechanisms of sensory processing, therefore, requires uncovering how connection patterns between neurons relate to their function. This has not been attempted with existing approaches, because neuronal functionality has to be assessed in the intact brain (electrode recordings, two-photon calcium imaging), while synaptic connectivity mapping is only feasible in brain slices (paired whole-cell recordings). To provide a solution to this problem, we have combined three powerful techniques that enable us first to visualise and characterise response properties of hundreds of neurons in the cortex with two-photon calcium imaging, then to identify the same neurons in slices of the same tissue using custom 3D image registration algorithms, and finally assay synaptic connections between a subset of these neurons with multiple whole-cell recordings. Applying this approach to mouse visual cortex, we found that connection probability was related to the similarity of visually driven neuronal activity. Neurons with the same preference for oriented stimuli connected at twice the rate of neurons with orthogonal orientation preferences. Neurons responding similarly to naturalistic stimuli formed connections at very high rates, while those with uncorrelated responses were rarely connected. Bidirectional synaptic connections were found more frequently between neuronal pairs with strongly correlated visual responses. Our results reveal a high degree of functional specificity of synaptic connections in local cortical circuits, and point to the existence of fine-scale subnetworks dedicated to processing related sensory information.

Selected publications

Optimization of population decoding with distance metrics.Hofer SB, Mrsic-Flogel TD, Horvath D, Grothe B, Lesica NA.Neural Netw. 2010 Aug;23(6):728-32. Epub 2010 May 5.

Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window. Holtmaat A, Bonhoeffer T, Chow DK, Chuckowree J, De Paola V, Hofer SB, Hübener M, Keck T, Knott G, Lee WC, Mostany R, Mrsic-Flogel TD, Nedivi E, Portera-Cailliau C, Svoboda K, Trachtenberg JT, Wilbrecht L. Nat Protoc. 2009;4(8):1128-44. Epub 2009 Jul 16.PMID: 19617885

A genetically encoded calcium indicator for chronic in vivo two-photon imaging. Mank M, Santos AF, Direnberger S, Mrsic-Flogel TD, Hofer SB, Stein V, Hendel T, Reiff DF, Levelt C, Borst A, Bonhoeffer T, Hübener M, Griesbeck O. Nat Methods. 2008 Sep;5(9):805-11.PMID: 19160515

Experience leaves a lasting structural trace in cortical circuits. Hofer SB, Mrsic-Flogel TD, Bonhoeffer T, Hübener M. Nature. 2009 Jan 15;457(7227):313-7. Epub 2008 Nov 12.PMID: 19005470

Massive restructuring of neuronal circuits during functional reorganization of adult visual cortex. Keck T, Mrsic-Flogel TD, Vaz Afonso M, Eysel UT, Bonhoeffer T, Hübener M. Nat Neurosci. 2008 Oct;11(10):1162-7. Epub 2008 Aug 31.PMID: 18758460

Valentin Nagerl