Transplantation of mesencephalic cell suspension in dopamine-denervated striatum of the rat .2. Effects on corticostriatal transmission

The present study has been designed to investigate whether intrastriatal implantation of mesencephalic dopamine (DA)-synthetizing neurons into the striatum (ST) of rats whose substantia nigra (SN) was previously destroyed by 6-hydroxydopamine (6-OHDA) restores the pattern of corticostriatal transmission from the medial prelimbic and sensorimotor cortices. In 6-month-old normal animals electrical stimulation of these two functionally unrelated cortices evoked a short latency and brief excitation in 81.6% of neurons recorded in the dorsolateral ST. This percentage decreased significantly (70.6%) in age-matched animals whose dopaminergic nigrostriatal pathway was unilaterally destroyed by 6-OHDA 3 months before recording. However a significant increase in neurons (36.9%) which could be simultaneously activated from the two cortices in comparison to intact rats was noted. In addition the lesion caused a significant decrease in the threshold current required to evoke activation of striatal neurons from the sensorimotor cortex. The increase in the number of striatal neurons responding simultaneously to cortical stimulations demonstrates that destruction of the dopaminergic nigrostriatal pathway causes st loss of the focusing action of DA on corticostriatal transmission. Transplantation of embryonic mesencephalic neurons appears to reestablish this action since the number of convergent responses was significantly decreased in grafted animals (23.5%) in comparison to denervated (36.9%) and sham-grafted (35.1%) animals. Furthermore, the grafts showed a trend to increase current intensities required to evoke activation of striatal cells from both cortices. The action of grafted mesencephalic neurons over prelimbic and sensorimotor cortical inputs to the dorsal ST could be involved in recovery of grafted animals in the correct execution of complex sensorimotor tasks requiring integration of different cortical signals within the ST. (C) 1997 Academic Press.