Project 1 [ended]

Cellular plasticity during high frequent stimulation in the subthalamic nucleus in mouse model of Parkinson’s disease

Deep brain stimulation (DBS) induces changes in the basal ganglia that can be regarded as a system of coupled plasticity mechanisms. Based on our previous experience in the analysis of developmental plasticity in sensory systems, we study a relatively wide spectrum of possible alterations during and after high frequency stimulation of the subthalamic nucleus (STN).

This project focuses on changes in the intrinsic functional properties of neurons and astrocytes in the STN and on glutamatergic and GABAergic synaptic transmission in STN target areas. We use slice preparations that largely conserve the connectivity of the basal ganglia which allows us to analyse pathophysiological processes on several levels, i.e. at subcellular level, in single neurons, neuron pairs and in neuronal nets. To this end, we apply electrical and optical stimulation techniques as well as patch clamp recording and vital imaging.

Currently, we compare DBS-related changes in the STN itself as opposed to changes in the substantia nigra pars reticulata (SNr). We have discovered two mechanisms that may account for STN depression: i) an increased failure rate in the action potential generation and ii) vesicle depletion in the axons of glutamatergic STN neurons. The latter mechanism takes place in the STN itself (axon collaterals) and in the target area. So far there is little evidence for a long term depression of the STN-nigral pathway.

Prof. Dr. Rosemarie GrantynProf. Dr. Rosemarie Grantyn, Principal Investigator
Charité – Campus Mitte
Cluster of Excellence NeuroCure & Department of Experimental Neurology
Synaptic Dysfunction Group
Robert-Koch-Platz 4
10115 Berlin
Tel.: +49-30-450 528 101
Fax: +49-30-450 528 952
E-mail: rosemarie.grantyn@charite.de