Electrophysiological analysis of synaptic transmission between intraocular hippocampus/locus coeruleus co-transplants

We have examined the establishment of functional connectivity between hippocampal and locus coeruleus co-transplants in oculo. Co-transplants were allowed to mature in oculo for 8-54 weeks following grafting and were subsequently removed from the anterior eye chamber for in vitro electrophysiological studies. Single hippocampal transplants in oculo have been shown to exhibit prolonged synaptic responses to local electrical stimulation, and similar responses were observed in hippocampal neurons following stimulation of the hippocampal portion of hippocampus-locus coeruleus co-transplants. Electrical stimulation of the locus coeruleus attenuated the afterhyperpolarization in hippocampal neurons elicited by the injection of depolarizing current, an effect that has been described previously in hippocampal slices following direct application of norepinephrine, and this effect was antagonized by pretreatment with the beta-adrenergic antagonist timolol. Stimulation of the locus coeruleus also produced both hyperpolarizing and depolarizing changes in the resting membrane potential in hippocampal neurons in 2- and 6-month-old co-transplants. In the 2-month-old co-transplants the responses were primarily depolarizing, and appeared to be mediated by a beta-adrenergic receptor, whereas in the 6-month-old co-transplants the responses were more varied. The results suggest that functional alpha- as well as beta-adrenergic receptors develop in oculo, and that the release of norepinephrine at nerve terminals in double grafts produces effects in the hippocampal neurons which are similar to those observed during superfusion of the hippocampal slice preparation with exogenous norepinephrine.