Evolution and function in serotonergic systems

Serotonergic systems of invertebrate and vertebrate centralnervous systems (CNS) are functionally similar in multiple characters.Serotonin (5-HT) neurons dispersed throughout the CNS of lophotrochozoaninvertebrates (molluscs and leeches) are analogous to vertebrate5-HT neurons concentrated in the raphe nuclei of mid- and hindbrain:they innervate specific central pattern generators and othercircuits of the CNS, receive feedback from them, and supportgeneral behavioral arousal. In both groups 5-HT regulates excitatorygain of CNS circuitry and uses similarly diverse 5-HT receptors.Marked contrast, however, exists for roles of 5-HT in regulationof appetite. Where invertebrate 5-HT neurons promote an appetitivestate, this role is supplanted in the vertebrates by a peptidergicnetwork centered around orexins/hypocretins, to which the roleof 5-HT in arousal is subordinate. In the vertebrates, 5-HThas appetite-suppressant properties. This is paralleled by differingcomplexities of mechanisms that bring about satiety. Lophotrozoansappear to rely on simple stretching of the gut, with no obviousfeedback from true nutrient stores. In contrast, vertebrateappetite is regulated by hypothalamic sensitivity to hormonalsignals reporting separately on the status of fat cells anddigestive activity, and to blood glucose, in addition to gutstretch. The simple satiety mechanism of a mollusc can be usedin value-based foraging decisions that integrate hunger state,taste, and experience (Gillette and others 2000). For vertebrates,where appetite and arousal are regulated by signals from long-livednutrient stores, decisions can be based on resource need goingfar beyond simple gut content, enabling value estimation andrisk assessment in the longer-term. Thus, connection of nutrientstorage depots to CNS circuitry mediating appetite may supplycritical substrate for evolving complexity in brain and behavior.This hypothesis may be tested in expanded comparative studiesof 5-HT and peptidergic functions in appetite and arousal.