Structural and functional impairment of adrenergic input to intraocular cerebellar grafts during thyroid hormone...

Embryonic cerebellae were transplanted to the anterior eye chamber of normal and thyroidectomized adult rats and were left in the eye to mature for 5 weeks. The cerebellar grafts received adrenergic innervation from the sympathetic ground plexus of the host iris. The density of adrenergic fibers innervating the grafts was reduced by approximately 50% in all thyroidectomized groups, without any effect on the fluorescence intensity or the morphology of individual nerve fibers. The reduction in adrenergic ingrowth was entirely prevented in grafts raised in similarly thyroidectomized recipients, which were substituted daily with thyroxine (100 micrograms/kg, SC). Electrophysiologically, there was no difference between the groups in terms of spontaneous firing rate of Purkinje neurons, recorded extracellularly from cerebellar grafts. However, there was a 10-fold decrease in the potency of catecholamines to inhibit the spontaneous neuronal activity in thyroidectomized hosts as compared to controls when applied either locally by micropressure ejection or by superfusion. Similar to the observed histologic changes in catecholamine innervation, the abnormal responsiveness of hypothyroid cerebellar neurons to locally applied catecholamines could be prevented by daily substitution with thyroxine in these animals. It is thus concluded that there is both structural and functional impairment of the adrenergic innervation of intraocular cerebellar grafts that underwent development under conditions of thyroid hormone deficiency.