Evidence for functional contact between cografted locus coeruleus and spinal cord in oculo: electrophysiological studies

Abstract

The functional consequences of the locus coeruleus innervation of the spinal cord are not yet clearly understood. In a recent histological study it was shown that intraocular spinal cord grafts will become innervated by tyrosine hydroxylase-positive nerve fibers from a cografted locus coeruleus. In the present study we use this intraocular model of the descending coeruleo-spinal pathway to investigate functional contact between locus coeruleus and the spinal cord. We have pharmacologically characterized the receptor mediation of norepinephrine-induced, as well as locus coeruleus-mediated depressions of spinal cord neurons grafted in oculo. We found that electrical stimulation of the locus coeruleus part of the double grafts predominantly caused an inhibition of cografted spinal cord neurons. Norepinephrine-induced inhibition of the firing rate of single grafted spinal cord neurons was antagonized by phentolamine, an α-adrenergic antagonist, but was unaffected by timolol, a β-adrenergic antagonist. Similarly, inhibition of the firing rate of grafted spinal cord neurons by stimulation of cografted locus coeruleus was antagonized by phentolamine but not by timolol. Interestingly, single spinal cord grafts were more sensitive to the depressant effects of perfused norepinephrine than was the spinal cord cografted with locus coeruleus. We conclude that spinal cord grafts can be functionally innervated by cografted locus coeruleus and that the noradrenergic inputs to spinal cord from cografted locus coeruleus are α-adrenergically mediated. Furthermore, the postsynaptic receptors in single spinal cord grafts appear to be supersensitive to norepinephrine application.