Early Cognitive Impairment in a Parkinson's Rat Model

"Basal ganglia are involved in selecting between competing signals, in particular when a dominant behaviour becomes inappropriate and a . new course of action is needed. In early stages of Parkinson's disease (PD) there is an unbalanced capability to manage self-paced . versus externally driven movements, or automatic-associated movements with respect to the intended voluntary movements. . Here, we examined the ability to switch form freely-selected, or internally driven (ID), to sensory-triggered, or externally cued (EC), . habituated motor acts, and vice versa, both in intact and in a PD rat model. The switching imposed after habituation evidenced an . interference action, or a main recruitment, of EC cerebello-cortical circuitry upon ID striatal-cortical circuit building. Such a recruitment . became almost exclusive following unilateral dopamine (DA) depletion of the striatal-cortical circuitry. In IEC transition, rats had to learn to . select the cued motor response and to inhibit the free choice habit. In EID transition, the novel demand to freely select motor acts, dependent . on striatal-prefrontal activity, interfered with well-learned EC behaviour, dependent on cerebello-cortical activity. The unilateral DA . striatal depletion enhanced the switch-induced performance differences in favour of IEC transition, DA depleted rats, in fact, were impaired . to produce an alternative motion when task switching required to change from an habitual behaviour, towards an alternative self paced . response. We hypothesize that EC behaviours have a more rigid imprinting on neuronal circuitry elicited with practice. Through . the somatosensory integration, the cerebello-cortical circuit marks EC circuit with information contained in the cue and induces a cue-based . action bias that interfere with, cue-free, ID striatal-cortical circuit building. . Brain MRI scans analysis revealed a lesion-dependent shrinkage of the right striatum, and an enlargement of the ipsilateral ventricle. . The comparative analysis of behavioural, TH+ and MRI data, could provide useful markers for monitoring pathological changes occurring . during early stages of PD. . "