Role of corticostriatal neurons in provoking the imbalance between the direct and indirect striatal output pathways after dopamingergic degeration

The striatum receives massive excitatory inputs from the cortex and is densely innervated by dopamine. Striatal projection neurons belong either to the direct or indirect pathways. Models of Parkinson's disease propose that dopaminergic degeneration imbalances both pathways. Indeed, in a previous study we showed that striatonigral neurons (direct pathway) are inhibited whereas striatopallidal neurons (indirect pathway) are activated in the striatum of rats rendered hemi-parkinsonian by a specific toxin. A sustained synaptic excitation originating from the cortex is required to enable discharge activity of striatal projection neurons. Therefore, imbalanced cortical activities may contribute to the imbalance between the direct and indirect pathways caused by dopaminergic denervation.

In preliminary experiments we were able to identify cortical neurons (IT-type), which preferentially innervate striatonigral neurons, versus cortical neurons (PT-type), which preferentially innervate striatopallidal neurons. We observed that the discharge activity of IT-type neurons is significantly decreased in the cortex ipsilateral to dopaminergic lesion. Therefore, the decreased activity of the direct pathway, observed in the parkinsonian brain, might be caused by a cortical imbalance and not only by the lack of dopamine in the striatum.

The aim of the present project is 1) to confirm this cortical imbalance with additional electrophysiological experiments, 2) to test whether antiparkinsonian therapy (apomorphine, levodopa) reverse it, 3) to develop anatomo-functional approaches to study it.