EMBRYONIC STRIATAL GRAFTS RESTORE NEURONAL-ACTIVITY OF THE GLOBUS-PALLIDUS IN A RODENT MODEL OF HUNTINGTONS-DISEASE

It has been demonstrated in rats that embryonic striatal grafts placed in the excitotoxically lesioned striatum establish neuronal connectio ns with the host globus pallidus. In order to determine whether the mo rphologically verified connections between the grafts and host are fun ctional, the present study investigated the effects of embryonic stria tal grafts on changes in the neuronal activity of the globus pallidus in rats with quinolinic acid-induced striatal lesions. The activity of pallidal neurons was determined by use of quantitative cytochrome oxi dase histochemistry and an electrophysiological technique. Striatal le sions induced an increase in both the cytochrome oxidase activity and the spontaneous firing rate of the globus pallidus ipsilateral to the lesions. Grafts derived from the lateral ganglionic eminence, but not the medial ganglionic eminence, reversed the lesion-induced increase i n the cytochrome oxidase activity of the globus pallidus with concomit ant reduction of apomorphine-induced rotational asymmetry. The lateral ganglionic eminence grafts also attenuate the increase in the firing rate of pallidal neurons in rats with striatal lesions. The present re sults provide evidence that striatal lesions lead to the loss of a ton ic inhibitory input to the globus pallidus with consequent increase in the activity of pallidal neurons, and that intrastriatal striatal gra fts reverse the altered activity of pallidal neurons. The findings str ongly suggest that embryonic striatal grafts functionally repair the d amaged striatopallidal pathway. (C) 1998 IBRO. Published by Elsevier S cience Ltd.