neocortex; synaptic circuits; pyramidal neurons; barrel cortex; primary somatosensory cortex; motor cortex; secondary somatosensory cortex; two photon microscopy; whole-cell recordings; electron microscopy; sensorimotor integration
Yamashita Takayuki, Pala Aurélie, Pedrido Leticia, Kremer Yves, Welker Egbert, Petersen Carl C H (2013), Membrane potential dynamics of neocortical projection neurons driving target-specific signals., in Neuron
, 80(6), 1477-90.
Schubert Vanessa, Lebrecht Daniel, Holtmaat Anthony (2013), Peripheral deafferentation-driven functional somatosensory map shifts are associated with local, not large-scale dendritic structural plasticity., in The Journal of neuroscience : the official journal of the Society for Neuroscience
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Gambino Frederic, Holtmaat Anthony (2012), Spike-timing-dependent potentiation of sensory surround in the somatosensory cortex is facilitated by deprivation-mediated disinhibition., in Neuron
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Neocortical microcircuits are thought to contribute significantly to the sophisticated computational ability of the mammalian brain. The mouse barrel cortex has emerged as a key model system for studying the structure, function and plasticity of synaptic circuits organised into neocortical columns. A single whisker deflection evokes neocortical activity, which at first is localised to its homologous barrel column. However, within the next milliseconds, sensory signals can propagate to other cortical areas, such as motor cortex (MI) and secondary somatosensory cortex (SII). Sensory information is therefore processed in a highly distributed manner in the neocortex allowing sensorimotor integration and the binding of polymodal sensory information, which are likely to be critical events during sensory perception and learning. Pyramidal neurons may be key drivers of such integrative processes, since they generate the primary output of the barrel cortex projecting to many cortical and subcortical targets. In this collaborative research project we will specifically investigate the C2 barrel column, a region known to process tactile information relating to the C2 whisker. Our experiments in this cortical column will define the structure, function and plasticity of supragranular pyramidal neurons with unprecedented precision. We will differentiate between pyramidal neurons projecting to MI and SII. First we will develop and refine methods for reliable dual fluorescent labelling of specific classes of pyramidal neurons based on classic retrograde tracers and recent developments in viral technology. Using these techniques, we will define the overall structural organisation of these projections from the barrel cortex. We will make complete three-dimensional reconstructions of local and long-range axonal arborisations together with the dendrites of the two classes of pyramidal neurons. The spatial distribution of synaptic boutons of the local axonal arbors will be analysed in relationship to the map of the whisker representation in the barrel cortex in order to shed light on their contribution to the local microcircuit. Serial section electron microscopy will be applied to determine the targets of these projections, as well as the innervation of the cell bodies and dendrites of the two classes of pyramidal neurons. Functional differences between these same classes of pyramidal neurons in the mouse barrel cortex will be studied through whole-cell recordings targeted through in vivo two-photon microscopy to fluorescently labelled neurons in awake mice and we will correlate the activity of these specific types of neurons in relationship to quantified sensorimotor behaviour. The synaptic connectivity of the neurons will be studied in vitro through a combination of multiple simultaneous whole-cell recordings and optogenetic methods applied to brain slices. Finally, we will investigate the differential synaptic plasticity of these two specific classes of pyramidal neurons through in vivo long-term two photon imaging of spine dynamics. We will measure spine turnover and investigate if specific manipulations differentially affect the two classes of pyramidal neurons.Together the data collected will provide a highly quantitative analysis of neocortical microcircuits, which will be essential in order to understand the synaptic mechanisms underlying behaviour and a variety of brain diseases. Besides providing an integrated data set on an identified sub-population of pyramidal neurons, the grant will allow a collective effort to develop new techniques both in structural and functional analyses of neocortical circuits.