CHAPTER 1.3 - The Neuronatomy of the Serotonergic System

Abstract

Abstract Neurons using serotonin as a neurotransmitter in the central nervous system are restricted to the brainstem, centered on the midline raphe nuclei, extending into the subnuclei of the lateral reticular formation. These neurons divide into two populations. A rostral group resides in the midbrain and rostral pons (caudal linear, dorsal and median raphe nuclei), with a major projection targeted to the forebrain. A caudal group located in the caudal pons and the medulla (raphe magnus, obscurus and pallidus nuclei, lateral medullary reticular formation) has a major projection targeted to the spinal cord. Both groups have projections to the brainstem. Subnuclei of the serotonergic system have distinctive afferent and efferent connections, with some entities more specifically linked to the sensory, motor or limbic systems. Serotonergic neurons segregate, based on their axonal morphology, into neurons with large varicose or small varicose axons, the latter being selectively sensitive to neurotoxins derived from amphetamines. This is the basis for a dual serotonergic projection system, which partially overlaps in certain structures such as the cerebral cortex. Small varicose axons form wide axonal arborization of various densities of synaptic boutons, sustaining a system of volume transmission. Large varicose axons form pericellular arrays of synaptic terminals surrounding the soma and proximal dendrites of selected neurons. Median raphe, raphe obscurus and raphe pallidus nuclei are the sources for serotonergic neurons with large varicose axons. As one of the diffuse aminergic systems of the brain, the serotonergic system segregates clearly into different entities, with subnuclei holding their own efferent and afferent connections, serotonergic neurons having different axonal morphologies and synaptic connections, and, finally, numerous serotonin receptor subtypes having different expression patterns across the brain.