Optogenetic manipulations of cortico-pallidal pathway impact specific aspects of motor behaviour in mice
Résumé
The classical model of basal ganglia (BG) network emphasizes a functional organization centered around the striatum and subthalamic nucleus as the main receiving areas of excitatory cortical inputs. However, recent anatomical studies revealed direct input projections from the cortex to the external globus pallidus (GPe) in many species including humans, suggesting that GPe also provides an entry for cortical information to the BG. When and how top-down cortical control of GPe takes place to support motor and cognitive functions remain an open question. Using an optogenetic approach, we first explored the behavioural effects of the cortico-pallidal pathway activation in normal BL6J mice. The excitatory channelrhodopsin-2 variant, ChR2(H134), was expressed in the secondary motor cortex (M2) area, the predominant source of cortical innervation to GPe. Mice expressing the fluorescent protein alone were used as controls. Unilateral photostimulation of cortical axon terminals in the GPe triggered contralateral circling while bilateral photostimulations improved acoustic sensorimotor gating (pre-attentive information filtering mechanism) and increased locomotor activity. The inhibitory chloride-conducting channelrhodopsin, iC++, was then expressed in M2 cortex to verify whether cortico-pallidal pathway is recruited in physiological conditions. Photoinhibition of cortico-pallidal axon terminals in GPe produced no change of spontaneous locomotor behaviour mice. By contrast, it reduced directed exploration assessed by spontaneous nose-poking behaviour in the operant chambers and delayed motor learning in the rotarod task. Similar behavioural effects were produced by optogenetic GPe modulations. Collectively, these findings provide the first evidence implicating the cortico-pallidal pathway in the modulation of specific aspects of motor function.
Domaines
NeurosciencesOrigine | Fichiers produits par l'(les) auteur(s) |
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