Electrical microstimulation of SNr has been shown recently to disrupt
REM sleep with atonia induced by activation of PPN.64 Moreover, activation of different foci within SNr produced variable dissociation of REM sleep and muscular atonia components. Intermingled throughout lateral SNr were microstimulation sites that attenuated REM sleep but not atonia, atonia but not REM sleep, Inhibitors,research,lifescience,medical or both components.64 In PD, degenerative loss of some PPN neurons combined with excessive and oscillatory GABAA-mediated inhibition of the others via the SNr afférents seems a plausible mechanism that may account for the frequent occurrence of RBD is this disease. Studies of experimental parkinsonism have also implicated in PPN in the pathophysiology Inhibitors,research,lifescience,medical of akinesia. Fibersparing lesions, pharmacological inactivation, and highfrequency stimulation of PPN in normal monkeys result in akinesia.65-67 The akinesia in PD might result from excessive GABAergic inhibitory outflow from GPi/SNr to PPN. This is suggested by the observation that akinesia in M.PTP-induced parkinsonism can be reversed by microinjection of the GABAA antagonist bicuculline into PPN.68 Basal forebrain
Inhibitors,research,lifescience,medical cholinergic neurons Loss of cholinergic neurons of the basal nucleus of Meynert (nBM) is common in PD, and can be associated with dementia.49,69,70 Of course, depletion of nBM. neurons is also seen – characteristically so – in Alzheimer’s disease (AD), which is by far the most common neurodegenerative disorder. The prevalence of AD exceeds that of PD by more than an order of magnitude.71 Reports linking dementia with ostensibly PD-induced cell loss in nBM Inhibitors,research,lifescience,medical have been appropriately careful to include only those cases in which Inhibitors,research,lifescience,medical the neurodegenerative changes in nBM were characteristic of PD rather than AD, ie, where LBs were demonstrable in surviving neurons and signs of AD – senile plaques and neurofibrillary tangles – were
minimal or absent.72 Amygdala: basolateral and cortical nuclei Pathological involvement of the basolateral these nucleus of the amygdala is also frequent in PD, although cell loss here is typically minimal despite extensive LB pathology.73,74 The glutamatergic neurons of this nucleus have linkages with both ventromedial prefrontal MLN8237 in vivo cortex and ventral striatum, and are believed to play significant roles in memory and learning.75,76 In PD patients with visual hallucinations, the proportion of basolateral neurons containing LB s was reported to be roughly twice that of patients who were free of hallucinations.73 An additional factor that may contribute to hyposmia in PD is the neuron loss and associated LB pathology that typically affects the cortical nucleus of the amygdala.73,74 The nucleus has powerful reciprocal connections with olfactory structures.