Cortical inputs and GABA interneurons imbalance projection neurons in the striatum of parkinsonian rats

N. Mallet
Journal of Neuroscience. 2006-04-05; 26(14): 3875-3884
DOI: 10.1523/jneurosci.4439-05.2006

Read on PubMed

1. J Neurosci. 2006 Apr 5;26(14):3875-84.

Cortical inputs and GABA interneurons imbalance projection neurons in the
striatum of parkinsonian rats.

Mallet N(1), Ballion B, Le Moine C, Gonon F.

Author information:
(1)Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5541,
Université Victor Segalen Bordeaux 2, 33076 Bordeaux, France.

The striatum receives massive cortical excitatory inputs and is densely
innervated by dopamine. Striatal projection neurons form either the direct or
indirect pathways. Models of Parkinson’s disease propose that dopaminergic
degeneration imbalances both pathways, although direct electrophysiological
evidence is lacking. Here, striatal neurons were identified by
electrophysiological criteria and Neurobiotin labeling combined with either
immunohistochemistry or in situ hybridization. Their spontaneous discharge
activity and spike response to cortical stimulation were recorded in vivo in
anesthetized rats rendered hemi-parkinsonian by 6-hydroxydopamine. We showed that
striatonigral neurons (direct pathway) were inhibited whereas striatopallidal
neurons (indirect pathway) were activated by dopaminergic lesion. We also
identified, with antidromic stimulations, corticostriatal neurons that
preferentially innervate striatonigral or striatopallidal neurons and showed that
dopaminergic depletion selectively decreased the spontaneous activity of the
former. Therefore, dopamine degeneration induces a cascade of imbalances that
spread out of the basal ganglia and affect the whole basal
ganglia-thalamo-cortical circuits. Fast-spiking GABA interneurons provide potent
feedforward inhibition of striatal projection neurons. We showed here that these
interneurons narrowed the time window of the responses of projection neurons to
cortical stimulation. In the dopamine-depleted striatum, because the intrinsic
activity of these interneurons was not altered, their feedforward inhibition
worsened the striatal imbalance. Indeed, the time window of the evoked responses
was narrower for striatonigral neurons and wider for striatopallidal neurons.
Therefore, after dopaminergic depletion, cortical inputs and GABA interneurons
might imbalance striatal projection neurons and represent two novel
nondopaminergic mechanisms that might secondarily contribute to the
pathophysiology of Parkinson’s disease.

DOI: 10.1523/JNEUROSCI.4439-05.2006
PMID: 16597742 [Indexed for MEDLINE]

Know more about