Our research group is focused on elucidating the complex brain circuitry underlying the pathophysiology of Parkinson’s disease (PD). Emphasis is placed on the analysis of the position of the thalamus within the basal ganglia model. In this regard, the caudal intralaminar nuclei are likely to play a key role as transversal circuits that exert a powerful modulation of basal ganglia function. Besides the thalamic modulation of basal ganglia circuits, ongoing projects are mainly dealing with: (i) characterization of pallidothalamic projections in animal models of PD, (ii) characterization of the thalamic innervation arising from the pedunculopontine nucleus and (iii) plastic changes induced within the striatal microcircuits after dopaminergic depletion.

A second project is dealing with the design of neurorestorative treatments for Parkinson’s disease by using the glial cell line-derived neurotrophic factor (GDNF). Although the potential usefulness of GDNF in PD is well known, there is a strong ongoing debate looking for the best way affording both an effective and safe GDNF brain delivery. In this regard, we are currently working on two different strategies: One strategy is focused on performing a controlled, long-term release of GDNF taking advantage of microspheres as drug delivery systems. In this regard, this project is carried out in close collaboration with the Department of Technical Pharmacology from the University of Navarra (contact person: Maria J. Blanco Prieto). Another feasible choice (to be soon implemented) is to undergo the controlled brain release of GDNF using regulatable AAV vectors.

Finally, a third research interest is represented by the study of a variety of striatal receptors with a heterodimeric architecture. Besides identifying pairs of these receptors as potential therapeutic targets, we will soon be conducting the validation of these targets by using a number of drugs specifically designed for approaching their respective targets. This is a collaborative project conducted under the guidance of Dr. Rafael Franco, from the University of Barcelona.

Basal ganglia circuits underlying the pathophysiology of PD.

Controlled release of the neurotrophic factor GDNF in animal models of PD.

Heterodimeric receptors in animal models of PD. Target selection and validation.