Specific functions of grafted locus coeruleus neurons in the kindling model of epilepsy

Grafts of fetal noradrenaline (NA)-rich locus coeruleus (LC) tissue implanted bilaterally into the hippocampus in 6-hydroxydopamine (6-OHDA) treated, hyperexcitable rats retard seizure development in hippocampal kindling. We report that bilateral intrahippocampal LC grafts failed to affect the severity of seizures when implanted in 6-OHDA-treated, already kindled rats. Furthermore, a noradrenergic hyperinnervation of the hippocampus, produced by grafting fetal LC tissue into the intact brain, did not influence hippocampal kindling development. Kindling leads to long-term reduction in basal hippocampal NA release from the intrinsic locus coeruleus system as monitored using intracerebral microdialysis. This deficit could be reversed by intrahippocampal LC grafts implanted into previously kindled rats. However, these unilateral grafts had no effect on the severity of the kindled convulsions despite a noradrenergic hyperinnervation of the hippocampus around the grafts. In conclusion, these data show a distinct functional specificity of intrahippocampal LC grafts in the kindling model of epilepsy. Similar to the intrinsic noradrenergic system, the grafted neurons have a major inhibitory influence on seizure development but are ineffective against established convulsions.