Project

cerebral cortex; somatosensory system; homeostatic plasticity; barrel; neuronal plasticity; synapse formation¨; sensory information; homeostasis

Lead
Lay summary
Sensory experience determines the way we perceive the world and ourselves. It is a lifelong functionality through which we develop our personality and which allows us during the various phases of our live, to act in accordance with what we learned and what we like to express. It turned out that there is a neuronal basis that allows the brain to adapt to alterations in sensory activity. We study the properties of this adaptation mechanism in a sensory system of the mouse that treats the information gathered by the whiskers on the snout. By the nature of its organization, this system allows modifying sensory activity without major perturbation for the animal and guides the observer's eye to the brain region where alteration can be analyzed in a very precise manner. The part of the brain we particularly study is the cerebral cortex. It is the region where sensory activity is transformed into a perception and where memory traces are induced. In the cortical area receiving the information from the whiskers, multi-neuronal arrangements (named "barrels) can be identified that correspond to single whiskers. We alter sensory activity using an electromagnetic device that induces movements of one or several whiskers for a period up to several days. Mice adapt to this stimulation rapidly, and, for example, maintain a normal sleep cycle during the period of stimulation. We have studied the effect of the stimulation in the cerebral cortex of adult mouse using morphological, neurophysiological, biochemical and molecular techniques. May be the most dramatic result is the demonstration that 24 hours of whisker stimulation induces the formation of synapses in the barrel, resulting in a 30% increase in the density of these connections between neurons. After stopping the stimulation, a part of the newly formed synapses remains forming a lasting trace of the period of modified sensory experience.Although the stimulation paradigm we use does not have a behavioral benefit for the animal, we propose that similar modifications may occur in a natural setting, Using molecular analyses we have identified a number of molecules that are up- or down regulated in the barrel cortex during the period of increased sensory stimulation. In the current series of experiments we will try to find out which type of neuron or glial cell is expressing these identified molecules.This series of investigations will identify who is doing what and may help identifying target cells for pharmacological intervention in diseases where increased neuronal activity leads to neuronal destruction - such as epilepsy or neuronal diseases where neuronal activity is decreased.

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Last update: 21.02.2013

Active participation

Number	Title	Start	Funding scheme

In the adult mouse, layer IV of the barrel cortex consists of excitatory and inhibitory interneurons that, together with the astrocytes react onto increased sensory stimulation in a very robust manner. We have shown that the structural modifications induced by 24 hours of continuous stimulation in the adult mouse include synapse formation (Knott et al., 2002), modified astrocytic coverage of excitatory synapses on spines (Genoud et al., 2006) and lead, at the functional level to a diminished response of the neurons upon deflection of the stimulated whisker (Quairiaux et al., 2007). These observations have led to the notion that layer IV of the adult somatosensory cortex is capable to react to an increased level of neuronal activity to maintain a level of homeostasis. It forms an example that illustrates the partnership between the various cellular elements that together regulate the neuronal network after a perturbation of its level of activity and turns the barrel cortex into a model to study homeostatic plasticity in the adult nervous system.To further contribute to the understanding of the molecular and structural basis for the homeostatic response we here formulated the following goals: i) to characterize the molecular pathways that are involved in the synaptic modifications underlying whisker-stimulation induced plasticity and to investigate how they are expressed in the different neuronal cell types in layer IV; and ii) to study alteration in the synaptic input to GABAergic neurons in stimulated barrels. The first set of experiments will be based on the analysis of the results of the micro-array study that we are currently performing in collaboration with Dr. Markus Ruegg of the Biozentrum of the University of Basel. Using bio-informatics we will identify the molecular pathways involved in the homeostatic process induced by whisker stimulation. Subsequently, we will investigate whether the different neuronal cell types modify gene expression in specific manners. These studies will involve in situ hybridization and immunohistochemistry.In the second set of experiments, serial section EM-analysis will be applied to investigate whether the input to GABAergic neurons is altered by the increased neuronal activity induced by the whisker stimulation paradigm. Two methods will be used to label and reconstruct individual GABAergic neurons: one is based on biocytin injection prior to stimulation; the second, on the use on mouse lines in which different GABAergic cell classes express GFP.