Project

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Structure, Function and Plasticity of the Barrel Cortex

Applicant Petersen Carl
Number 127289
Funding scheme Sinergia
Research institution Brain Mind Inst., Faculty of Life Sciences SV-BMI-BMI-GE EPFL
Institution of higher education EPF Lausanne - EPFL
Main discipline Neurophysiology and Brain Research
Start/End 01.01.2010 - 31.12.2013
Approved amount 1'000'000.00
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Keywords (11)

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

Lay Summary (English)

Lead
Lay summary
Sensory information is actively gathered by animals. For example, we make eye movements to look at points of interest in the world around us. Through these self-generated movements we therefore determine a large part of the sensory information falling upon the retina. Similarly for touch, we actively move our fingers to explore the shape of objects and to feel their textures. Normal sensory perception therefore clearly involves important coordination of sensory processing with motor control.Important aspects of sensory perception depend upon the neocortex and the activity of neurons within the neocortical microcircuits is thought to underlie the impressive processing power of the mammalian brain.In this project we will explore how primary and secondary somatosensory cortices interact together with motor cortex in order to further our understanding of sensorimotor integration in the mouse. Studying mice enables investigation of underlying genetic determinants, which will be of increasing importance over the next decades as we begin to understand causal mechanisms of brain function and brain diseases.We will focus our research on cortical areas involved in processing tactile information from the mystacial vibrissae, which form an important sensory modality for mice. We will develop techniques for multicolor fluorescent labelling of neurons in primary somatosensory barrel cortex, with one color for neurons projecting to secondary somatosensory cortex and another color for neurons projecting to motor cortex. We will study the structure of these neurons in terms of somatic locations, dendritic structure, axonal structure and synaptic structure. We will also study the functional operation of these different classes of neurons to investigate if they have different activities during different behaviours. Finally, we will examine if they change their structure and function in different ways following experimental manipulations to induce plasticity.The project is therefore aimed at deepening our understanding of sensorimotor coordination in the mammalian brain through highly specific and detailed investigations. The research will shed light on fundamental aspects of brain function, processes which may well be affected by a large number of brain diseases.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Membrane potential dynamics of neocortical projection neurons driving target-specific signals.
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.
Peripheral deafferentation-driven functional somatosensory map shifts are associated with local, not large-scale dendritic structural plasticity.
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, 33(22), 9474-87.
Spike-timing-dependent potentiation of sensory surround in the somatosensory cortex is facilitated by deprivation-mediated disinhibition.
Gambino Frederic, Holtmaat Anthony (2012), Spike-timing-dependent potentiation of sensory surround in the somatosensory cortex is facilitated by deprivation-mediated disinhibition., in Neuron, 75(3), 490-502.

Associated projects

Number Title Start Funding scheme
131089 Synaptic Mechanisms of Sensory Perception and Associative Learning 01.04.2010 Project funding (Div. I-III)
139229 Platform for integrated mouse behavior (PIMB) 01.12.2011 R'EQUIP
153448 Activity-dependent functional and structural plasticity in the somatosensory cortex in vivo 01.04.2014 Project funding (Div. I-III)
139219 Multi-user two-photon microscope facility for advanced neuron imaging in-vivo and in-vitro 01.07.2012 R'EQUIP
120685 Experience-dependent structural plasticity of synapses in vivo 01.04.2008 Project funding (Div. I-III)
108246 Structural basis for neuronal plasticity in the adult somatosensory cortex 01.04.2005 Project funding (Div. I-III)
116027 Synaptic mechanisms of sensory perception and associative learning 01.04.2007 Project funding (Div. I-III)
135631 Long-term potentiation and the modification of synaptic structures in vivo 01.04.2011 Project funding (Div. I-III)

Abstract

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.
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