Deficit of striatal parvalbumin-reactive GABAergic interneurons and decreased basal ganglia output in a genetic rodent model of idiopathic paroxysmaldystonia
M. Gernert et al., Deficit of striatal parvalbumin-reactive GABAergic interneurons and decreased basal ganglia output in a genetic rodent model of idiopathic paroxysmaldystonia, J NEUROSC, 20(18), 2000, pp. 7052-7058
The underlying mechanisms of various types of hereditary dystonia, a common
movement disorder, are still unknown. Recent findings in a genetic model o
f a type of paroxysmal dystonia, the dt sz mutant hamster, pointed to stria
tal dysfunctions. In the present study, immunhistochemical experiments demo
nstrated a marked decrease in the number and density of parvalbumin-immunor
eactive GABAergic interneurons in all striatal subregions of mutant hamster
s. To examine the functional relevance of the reduction of these inhibitory
interneurons, the effects of the GABA(A) receptor agonist muscimol on seve
rity of dystonia were examined after microinjections into the striatum and
after systemic administrations. Muscimol improved the dystonic syndrome aft
er striatal injections to a similar extent as after systemic treatment, sup
porting the importance of the deficiency of striatal GABAergic interneurons
for the occurrence of the motor disturbances. The disinhibition of striata
l GABAergic projection neurons, as suggested by recent extracellular single
-unit recordings in dt(sz) hamsters, should lead to an abnormal neuronal ac
tivity in the basal ganglia output nuclei. Indeed, a significantly decrease
d basal discharge rate of entopeduncular neurons was found in dt(sz) hamste
rs. We conclude that a deficit of striatal GABAergic interneurons leads by
disinhibition of striatal GABAergic projection neurons to a reduced activit
y in the entopeduncular nucleus, i.e., to a decreased basal ganglia output.
This finding is in line with the current hypothesis about the pathophysiol
ogy of hyperkinesias. The results indicate that striatal interneurons deser
ve attention in basic and clinical research of those movement disorders.