LETTER TO NEUROSCIENCE IMPACT OF D1-CLASS DOPAMINE RECEPTOR ON STRIATAL PROCESSING OF CORTICAL INPUT IN EXPERIMENTAL PARKINSONISM IN VIVO K. Y. TSENG,* L. A. RIQUELME AND M. G. MURER Departamento de Fisiologı ´a, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Buenos Aires 1121, Argentina Abstract—Recent in vivo electrophysiological studies suggest that chronic dopamine depletion alters profoundly the firing pattern of basal ganglia neurons. These changes may disrupt the processing of cortical information flow from the striatum to the output nuclei, and presumably underlie the clinical manifes- tations of Parkinson’s disease. We have recently reported that chronic nigrostriatal lesions induce changes in the functional state of striatal medium-spiny neurons (MSNs) that could facil- itate spreading of cortical synchronous activity (approximately 1 Hz) to striatal target nuclei. Here we show that systemic administration of D1 dopamine agonists was sufficient to re- store the changes induced by chronic nigrostriatal lesions on striatal neuronal activity into the normal state. Following sys- temic administration of SKF38393 or SKF81279 the membrane potential of striatal MSNs was upheld into a more hyperpolar- ized value and action potential firing probability decreased. D1 agonists also increased the latency to the cortically driven pla- teau depolarization and reduced the peak potential of the short latency depolarizing postsynaptic response to a more hyperpo- larized value. The present study provides in vivo evidence indi- cating that pharmacological stimulation of D1-class dopamine receptors can modulate the flow of cortical information through the striatum in the parkinsonian state. © 2003 IBRO. Published by Elsevier Ltd. All rights reserved. Key words: striatum, D1 dopamine receptor, in vivo intracel- lular recordings, 6-OHDA, basal ganglia, Parkinson’s dis- ease. It is conventionally accepted that part of the influence of dopamine (DA) on sensoriomotor and cognitive functions is related to its modulation on striatal processing of cortical input (Albin et al., 1989; Hollerman et al., 2000). Both DA containing fibers and cortical glutamatergic inputs con- verge at the dendrites of striatal projections cells, the me- dium-spiny neurons (MSNs) (Smith et al., 1998). Striatal MSNs recorded in vivo exhibit spontaneous depolarizing– hyperpolarizing membrane potential fluctuations (namely “up states” and “down states” respectively; Wilson, 1993), which are tightly coupled to cortical synchronous activity (approximately 1 Hz; Mahon et al., 2001; Tseng et al., 2001a). The strength of this cortical–striatal correlation was not affected after chronic nigrostriatal lesions (Tseng et al., 2001a). However, striatal neurons recorded from chronic nigrostriatal lesioned rats display a more depolar- ized membrane potential, and a significant increase in the probability of firing during the up states (Tseng et al., 2001a). Because the “up states” are perceived as “en- abling events,” during which synchronously depolarized MSNs can decode afferent activity into sequences of ac- tion potentials, these changes in the membrane potential of striatal MSNs may facilitate the transmission of slow synchronous cortical activity to the basal ganglia output nuclei (Tseng et al., 2001a). Indeed, single unit recordings performed in animal models of Parkinson’s disease re- vealed that basal ganglia output nuclei neurons tend to discharge in bursts and to show periodic oscillations in the firing rate (Sanderson et al., 1986; MacLeod et al., 1990; Burbaud et al., 1995; Murer et al., 1997; Wichmann et al., 1999; Raz et al., 2000; Tseng et al., 2001b). Although the mechanisms resulting in this oscillatory activity have so far been speculated, there is evidence indicating that stimu- lation of striatal D1-class DA receptors restores activity in the output nuclei into the normal state (Tseng et al., 2000). Thus, it is possible that the changes induced by chronic nigrostriatal lesions on striatal neuronal activity would be reverted to the normal state by pharmacological activation of D1-class DA receptor. Here, the effects of systemic administration of D1 agonists (1-phenyl-2,3,4,5-tetrahydro- (1H)-3-benzazepine-7,8-diol [SKF38393] and SKF81297) on both the spontaneous membrane potential fluctuation of striatal neurons and their response to frontal cortical stim- ulation were studied by in vivo intracellular recordings in 6-hydroxydopamine (6-OHDA)-lesioned rats. EXPERIMENTAL PROCEDURES Lesions The animals were maintained on a 12-h light/dark cycle, with food and tap water available ad libitum. Unilateral lesion of mesence- phalic dopaminergic neurons was obtained following a published protocol (Murer et al., 1997). Briefly, male adult Sprague–Dawley rats weighing 190 –220 g were anesthetized with pentobarbital *Correspondence to: K. Y. Tseng, MD, PhD, Center for Neurophar- macology and Neuroscience, Office TSX-110A, Albany Medical Col- lege, MC-136, Albany, NY 12208, USA. Tel: +1-518-262-5903 or 0688; fax: +1-518-262-5799. E-mail address: tsengky@mail.amc.edu (K. Y. Tseng). Abbreviations: DA, dopamine; dPSP, depolarizing postsynaptic potential; LLD, long-lasting depolarization; LLH, long-lasting hyperpolarization; MSNs, medium-spiny neurons; SKF38393, 1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol; SKF81279, 6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine; 6-OHDA, 6-hydroxydopamine. Neuroscience 123 (2004) 293–298 0306-4522/04$30.00+0.00 © 2003 IBRO. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.neuroscience.2003.10.005 293