Unilateral dopamine denervation blocks corticostriatal LTP

The nigrostriatal dopaminergic projection is crucial for the striatal proce ssing of motor information received from the cortex. Lesion of this pathway in rats causes locomotor alterations that resemble some of the symptoms of Parkinson's disease and significantly alters the excitatory transmission i n the striatum. We performed in vitro electrophysiological recordings to st udy the effects of unilateral striatal dopamine (DA) denervation obtained b y omolateral nigral injection of 6-hydroxydopamine (6-OHDA) in the formatio n of corticostriatal long-term potentiation (LTP). Unilateral nigral lesion did not affect the intrinsic membrane properties of striatal spiny neurons . In fact, these cells showed similar pattern of firing discharge and curre nt-voltage relationship in denervated striata and in naive controlateral st riata. Moreover, excitatory postsynaptic potentials (EPSPs) evoked by stimu lating corticostriatal fibers and recorded from DA-denervated slices showed a pharmacology similar to that observed in slices obtained from controlate ral intact striata. Conversely, in magnesium-free medium, high-frequency st imulation (HFS) of cortico-striatal fibers produced LTP in slices from nond enervated striata but not in slices from 6-OHDA-denervated rats. After dene rvation, in fact, no significant changes in the amplitude of extra- and int racellular synaptic potentials were recorded after the conditioning HFS. Th e absence of corticostriatal LTP in DA-denervated striata might represent t he cellular substrate for some of the movement disorders observed in Parkin son's disease.