Neural pathways and neurotransmitters affecting melatonin synthesis.

In addition to its sympathetic innervation, a mammalian pineal gland also receives a distinct central pinealopetal innervation. Earlier studies in rat have established that the photic signals originating in the retina pass via the retinohypothalamic tract to the suprachiasmatic nucleus, to the tuberal hypothalamus, over medial forebrain bundle, reticular formation, and upper thoracic interomediolateral cell column to the superior cervical ganglion, whose postganglionic sympathetic fibers, traveling along the tentorium cerebelli, enter the pineal gland via the conarian nerve. Recent electron microscopic analyses of the pineal gland of several mammalian species have revealed intrapineal nerve terminals different from the sympathetic ones. In addition, lesion experiments performed in the habenular nuclei or the posterior commissure support the central origin of these terminals. The intact sympathetic innervation, the functional beta-adrenergic receptors, and the appropriate level of norepinephrine are all essential prerequisites for the circadian pattern of melatonin synthesis. However, other receptors such as alpha-adrenergic, D2-dopaminergic, GABAergic, benzodiazepinergic, and glutamatergic receptors and their agonists are also able to modulate the synthesis of melatonin, and this function depicts dramatic species variation. The impact of pinealopetal projections and intrapineal neurons on the physiological and biochemical aspects of pineal functions awaits clarification.