The behavioral and neurophysiologic effects of acute dopamine receptor blockade in the macaque striatum

摘要: The pathophysiology of Parkinson's disease (PD) has long been attributed to dopamine (DA) loss in the striatum. However, it remains unclear whether simple underactivation striatal DA receptors is sufficient induce parkinsonian signs. To test this hypothesis, we performed unilateral infusions cis-flupenthixol (cis-flu; D1/D2 antagonist) into macaque putamen, while a reaching task. Twenty-six cis-flu and three saline were across hemispheres two macaques. Neuronal local field potential activity was recorded simultaneously from cortex, globus pallidus externa (GPe), interna (GPi) during most infusions. task required each make visually-cued movements target for reward. then return its hand home position without external cues. Injection-related slowing movement initiation or execution thought reflect akinetic- bradykinetic-like effects, respectively. Following 8/26 infusions, macaques exhibited marked self-generated (95% increase). This severe behavioral effect externally-cued also prolonged following 9/26 6/26 injections, but only by 20% 15% In general, akinetic-like effects occurred twice as often (p<0.05, 2= 4.1). Interestingly, akinetic bradykinetic could be elicited independently. addition affecting behavior, intrastriatal receptor blockade reduced resting peri-movement cortex suppressed GPe activity. Burstiness, synchrony, oscillatory increased well. Oscillatory GPi. conclusion, suppression signs, severely movements. Furthermore, distinct parkinsonian-like signs independently, suggesting that separate may have unique pathophysiologic substrates. Intrastriatal induced changes cortical BG consistent with findings state. many these neuronal specific implicating an important role development