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Josef Aaron Avshalomov

The role of NMDA receptor subunits in the regulation of synaptic plasticity in dorsomedial striatum in a model of paroxysmal dystonia

Universität Rostock, 2007

Abstract: Dystonias are movement disorders whose pathomechanism is largely unknown. The dtsz dystonic hamster mutant represents a model of primary paroxysmal dystonia, where alterations of striatal interneuron density and long term potentiation were described (Köhling et al., 2004, Gernert et al., 2000). In the present thesis, using corticostriatal slices, we explore in more detail whether long-term potentiation (LTP) and long-term depression (LTD) are shifted by a) behavioural stimulation or b) ontogenetic maturation using different stimulation protocols in the cortico-striatal synaptic pathway. The third aim of the thesis was c) to explore the role of NMDA receptors and their subunits in synaptic plasticity changes occurring with dystonia. Field extracellular recordings were conducted in dorsomedial striatum, and white matter was stimulated. Short and long term plasticity as well as input-output relationships were analysed. The main findings were: a. The occurrence of enhanced synaptic plasticity is not dependent on behavioural stimulation, while changes in excitability are. b. Ontogenetic maturation increases the dynamic range of synaptic plasticity under normal conditions, which is infringed in animals with dystonia, even though the symptoms have remitted. c. In dystonic tissue, LTP is dependent on NR2A, wheras in normal tissue, it depends on NR2B receptors. In conclusion, the functional shifts in NR2A vs. NR2B involvement in synaptic corticostriatal plasticity may be instrumental in the pathogenesis of dystonia in the dtsz model.

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