The cellular logic of sensory circuits
Professor of Systems Neuroscience
tel: +44 20 3108 8014
Perhaps the two most compelling features of the brain are its connectivity and myriad cell types. Our lab is focused on studying cell-to-cell diversity within and across different neuronal classes and networks, in the context of local and long-range connectivity. It is our view that only a detailed quantitative understanding of the heterogeneity in connectivity and cellular composition of the network can elucidate key principles underlying the design and operation of neuronal circuits in the normal and diseased brain.
From a technical standpoint, we employ a variety of approaches, some of which are multidisciplinary and/or were developed in our lab. These include 3D electron microscopic analysis, in vitro and in vivo single and multi-cell targeted recordings, whole-brain connectivity mapping of recorded cells, optogenetics, modelling, and behaviour. Our lab works almost exclusively on mice, which offer a tractable experimental system for establishing causal relationships between the functional connectivity of mammalian neuronal circuits and behaviour.
Our lab is focused on dissecting brain function at the cellular level using two model systems. The primary visual cortex is perhaps the most studied cortical area. At a functional level it is highly plastic and contains functionally and biophysically diverse cell types. Many of these receive input from higher-order associational areas, including retrosplenial cortex. We are focused on understanding how the response properties of individual cortical cells emerge from connectivity, with emphasis on the functional relationship between these two cortical areas in the context of visual and non-visual sensory processing.
The glomerular circuit of the olfactory bulb is another model system of choice, as local networks can readily be identified and genetically targeted from one mouse to the next. Compared to cortex, the glomerulus is anatomically and functionally relatively simple; its cellular composition is well understood. However the intrinsic properties of glomerular neurons vary according to the glomerulus in which they receive odour input. This intrinsic biophysical diversity is known to depend on the identity of the receptor neurons that relay sensory information to the glomerulus. We therefore use this system to investigate the functional significance of intrinsic diversity and plasticity in the context of olfactory information processing in the behaving animal.
- Group Members
Zara Allardyce Research Technician
Edward Bracey Research Associate
Lee Cossell Research Associate
Sepi Keshavarzi Research Associate
Chris Puhl Research Associate
Sara Rolle-Sonora PhD student
Charly Rousseau Senior Research Associate
Molly Strom Senior Research Associate
Chryssanthi Tsitoura Research Associate
Mateo Velez-Fort Research Associate
- Selected Publications
- aMAP is a validated pipeline for registration and segmentation of high-resolution mouse brain data. Niedworok CJ, Brown AP, Jorge Cardoso M, Osten P, Ourselin S, Modat M, Margrie TW. Nature Communications 2016 Jul 7;7:11879. doi: 10.1038/ncomms11879.
- Chabrol, F.P., Arenz, A., Wiechert, M.T., Margrie, T.W., DiGregorio, D.A. (2015) Synaptic diversity enables temporal coding of coincident multi-sensory input in single neurons. Nature Neuroscience 18 (5) p718-27.
- Rancz, E.R., Moya, J., Drawitsch, F., Brichta, A.M., Canals, S., Margrie, T.W. (2015) Widespread vestibular activation of rodent cortex. Journal of Neuroscience 35 (15) p5926-34.
- Velez-Fort, M., Rousseau, C., Niedworok, C., Wickersham, I.R., Rancz, ER., Strom, M., Margrie, T.W. (2014) The stimulus selectivity and connectivity of layer 6 principal cells reveals cortical microcircuits underlying visual processing. Neuron 83, p1431-43.
- Chadderton, P., Williams, S.R., Schaefer, A.T., and Margrie T.W. (2014) Sensory-evoked synaptic integration in cerebellar and cerebral cortical neurons. Nature Reviews Neuroscience 15 (2) p71-83.
- Bracey, E., Pichler, B., Schaefer, A.T., Wallace, D.H. and Margrie T.W. (2013) Perceptual judgments and chronic imaging of altered odor maps indicate comprehensive template matching in rodent olfaction. Nature Communications 4:2100 DOI: 10.1038/ncomms3100.
- Osten, P. and Margrie, T.W. (2013) Mapping brain circuitry with a light microscope. Nature Methods 10 (6) p515-23.
- Angelo, K., Rancz, E.A., Pimentel, D., Hundahl, C., Hannibal, J.,
Fleischmann, A., Pichler, B., and Margrie, T.W. (2012) A biophysical
signature of network affiliation and sensory processing in mitral cells.
Nature 488, 7411 p375-8.
- Rancz, E.A., Franks, K.M., Schwarz, M., Pichler, B., Schaefer, A.T., and Margrie T. W. (2011) Transfection via whole-cell recordings in vivo: Bridging single-cell physiology, genetics and connectomics. Nature Neuroscience 14 (4) p527-532.