Betreuer: Prof. Dr. Rüdiger Köhling
MSc Josef Avshalomov
(e-mail: long_term_potentiation_forever@yahoo.com.au )
The role of NMDA receptor subunits in the regulation of synaptic
plasticity in dorsomedial striatum in a model of paroxysmal dystonia.
Dystonias are movement
disorders whose pathomechanism is largely unknown. The dtsz dystonic hamster
mutant represents a model of primary paroxysmal dystonia, where alternations 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) is 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 subnunits 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.