Deficits in the attentional control of posture and complex movements in a rat model of early state, multisystem Parkinson’s disease

Parkinson’s disease (PD) is increasingly recognized as a multisystem neurodegenerative disorder. Loss of basal forebrain cholinergic neurons occurs as early as the loss of midbrain dopaminergic neurons and is hypothesized to contribute to the cognitive deficits in PD. PD patients also suffer from a propensity for falls and associated impairments in posture control and movement efficacy; these symptoms do not benefit from L-DOPA treatment. Our research hypothesizes that attentional deficits caused by loss of cholinergic neurons interact with limitations in posture control and movement efficacy caused by dopaminergic cell loss to cause falls. We therefore generated rats with a 50-70% loss of the cortical cholinergic input system and a mild loss of dopaminergic afferents of the dorsal striatum (‘dual’ lesions) to model the individual and combined loss of neurons in these two key neuronal systems affected early in PD. To assess posture control and complex movements demanding attentional supervision, we developed the Michigan Complex Motor Control Test (MCMCT). In addition to several control procedures, the core element of this test battery consists of 2-m long rotating (10 rpm) square or round rods, placed at zero, 22.5° or 45° angles to the vertical plane. Animals are trained to traverse these rods to enter the home cage. Performance was assessed using the Mobility Error Index (MEI) that assigns point-scale values for missteps, limb slips and falls. Traversing these rods requires continuous attention to rotation speed, posture and limb coordination. Furthermore, and importantly, the ability of an olfactory distractor (almond extract, placed 10 cm below the rod at about the 1-m mark) to evoke freezing and falls was assessed. To obtain an independent measure of their attentional capacity rats also practiced daily the Sustained Attention Task (SAT). Dual lesions resulted in near chance SAT performance. The lesions did not produce impairments in motor functions as tested by standard rodent neurological tests, a ladder task, and the vermicelli test. MCMCT testing revealed that dual lesions resulted in a greater number of falls and higher MEI scores relative to shams. Presentation of the olfactory distracter caused missteps and transient lower body imbalances that duals were unable to overcome leading to increased falls. Collectively, this evidence supports the usefulness of the MCMCT for research concerning the neuronal basis of falls and associated impairments in movement control, and indicates that limited dual loss in cholinergic and striatal dopamine systems disrupt posture control and movement efficacy in conditions requiring attentional supervision.