Neuroanatomy, Nucleus Raphe

Excerpt

The raphe nuclei are positioned midline in the brainstem throughout the midbrain, pons, and medulla. These nuclei contain primarily serotonergic neurons, which release serotonin (5-hydroxytryptamine) with autocrine and paracrine effects, as well as synaptic connections. Serotonin generation comes from L-tryptophan via a two-step process catalyzed by tryptophan hydroxylase and L-aromatic amino acid decarboxylase. Upon release, serotonin binds a 5-HT receptor postsynaptically, subtypes of which exert different physiologic effects. Presynaptic 5-HT autoreceptors modulate the subsequent release of serotonin. The serotonin reuptake transporter (SERT) is responsible for presynaptic reuptake. Serotonin primarily metabolized by monoamine oxidase.

The more rostral nuclei located in the midbrain and rostral pons – caudal linear nucleus, dorsal raphe, and median raphe – have projections which extend to forebrain structures. These projections modulate behavioral and emotional functioning, including mood regulation, memory, and sleep-wake cycle. The caudal nuclei of the caudal pons and medulla– raphe magnus, raphe obscurus, and raphe pallidus – primarily project to spinal cord structures; this occurs via parallel projections to ventral, intermediate, and dorsal columns. They modulate nociception and movement.

A decrease of serotonergic input to the limbic system has been the longstanding and primary model for the pathogenesis of major depression. Decreased synthesis of serotonin, low-affinity binding to post-synaptic receptors, increased the response of presynaptic autoreceptors, and rapid degradation of serotonin all carry links to clinical depression. These differences in physiology are often due to genetic polymorphisms, explaining increased susceptibility in patients with a family history of depression. While the pathogenesis of depression is understood to be multifactorial in most patients, augmentation of serotonergic transmission with selective serotonin reuptake inhibitors (SSRIs) has been the longstanding first-line treatment for depression.