Lab Projects

Here you can read an introduction to our scientific projects:

Cell type - specific impairment of structural plasticity related to motor activity and motor learning in primary motor cortex

One major hallmark of ALS is the degeneration of upper motor neurons, a feature that is currently not well understood. To address the question whether neurons in motor cortex of ALS transgenic mice are impaired, we monitor their structural plasticity related to motor activity and to motor learning (Fig. 1A-D). To this end we use transgenic mice that sparsely label a subset of pyramidal neurons in cortex and cross them with known mouse models for ALS. We then employ in vivo two-photon imaging to monitor the dynamics of dendritic spines of neurons in motor cortex, both during short intervals in behaving mice and chronically over weeks, while mice perform a learning task. We furthermore ask whether different cell populations in motor cortex, based on their projection areas, are affected to a similar degree.

Response properties of astrocytes

The major glial cell type in the brain are astrocytes. These important glia cells are known serve a myriad of supportive roles and have been proposed to contribute to non cell - autonomous processes causing neurodegeneration in ALS. In this project we address the question whether physiological response properties of cortical astrocytes are altered during the course of the disease and by what molecular and cellular mechanism these changes are caused (Fig. 1 E,F).

Cell type - specific functional impairment in primary motor cortex of ALS transgenic mice

Changes in neuronal structural plasticity are very likely to result in functional alterations. We, hence, chronically monitor neuronal response properties associated with a number of behavioural parameters using two-photon calcium imaging in behaving mice (Fig. 1G). We then ask whether certain molecular changes result in alterations of these neuronal response properties, thereby aiming at unraveling the sequence of molecular events leading to motor neuron degeneration in vivo. This approach enables to link molecular changes to functional impairment at single cell - and high temporal resolution. These experiments are not only key to the characterization of upper motor neuron degeneration but, moreover, lay a foundation for future interventional approaches, as they allow us to comprehensively assess the efficacy of interventions in a multiparametric and cell type - specific manner in vivo.
 
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Director

Prof. Dr.

Reinhard Hohlfeld

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Prof. Dr.

Martin Kerschensteiner

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Group Leader

Dr.

Sabine Liebscher

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