Synchronous oscillations and phase reorganization in the basal ganglia during akinesia induced by high-dose haloperidol

Abstract

Movement disorders such as tremor and akinesia observed in Parkinson's disease have been attributed to dopamine (DA) depletion in the basal ganglia. The changes in subcortical neuronal discharge patterns that follow DA depletion have been a matter of much discussion. Here, we implanted rats with chronic recording electrodes bilaterally in the striatum (CPu) and external globus pallidus (GPe), and induced both acute and repeated DA blockade by administration of high-dose haloperidol. Recordings were made in baseline states, as well as before and after haloperidol injections, which rendered rats akinetic. The immediate physiological effect of pharmacological DA blockade was the development of prominent oscillatory firing in the 6-8 Hz range in both CPu and GPe. Importantly, this oscillatory pattern was not accompanied by consistent changes in the firing rate of either CPu or GPe neurons. Cross-correlation analysis further indicated that neurons within the CPu and GPe fired synchronously after DA blockade. Furthermore, although phase lags between neuronal discharges in the GPe and CPu were uniformly distributed prior to haloperidol administration, CPu significantly lagged GPe discharges after repeated DA blockade. Our results demonstrate that acute DA blockade is sufficient to produce synchronous oscillatory activity across basal ganglia neuron populations, and that prolonged DA blockade results in phase lag changes in pallidostriatal synchrony.