Cholinergic innervation and function in the mammalian pineal gland

Besides the noradrenergic sympathetic system originating from the superior cervical ganglion, a cholinergic innervation of the mammalian pineal gland has been studied over the past three decades. In 1961, it was shown that lesion of the parasympathetic greater superficial petrosal nerve of the monkey resulted in degeneration of nerve fibers in the pineal gland. This was supported by ultrastructural studies of nerve terminals within the pineal gland, demonstrating the presence of cholinergic terminals containing small clear transmitter vesicles. Biochemical studies further showed the presence of the enzyme acetylcholinesterase in several mammalian species. During the last decade, several advanced and more elaborate technologies have been developed, allowing pinealogists to establish the presence of cholinergic fibers and their receptors. Thus, choline acetyltransferase was shown in bovine pineal by immunohistochemistry. Muscarinic and nicotinic receptors were identified, characterized, and localized. Gene expression of receptors was visualized, and the receptor-mediated effector systems and functions were elucidated. Taken together, the present data suggest the presence of a cholinergic innervation of the mammalian pineal gland originating in peripheral parasympathetic ganglia. However, some of the neuronal projections to the pineal gland with origin in the brain (the central innervation) might also be cholinergic. The cholinergic nerve fibers enter the gland, where they are located both in the perivascular spaces and between the pinealocytes. Some of the terminals make synapses on pinealocytes or intrapineal neurons. The released acetylcholine from the terminals interacts with the receptors, then alters the cascade of receptor-mediated events, which results in decreased N-acetyltransferase enzyme activity, thus leading to decreased melatonin synthesis. This counterbalance mechanism between the sympathetic noradrenergic and the cholinergic systems maintains the homeostasis of pineal functions.