Hormonal and synaptic influences of serotonin on adult neurogenesis

Abstract

New neurons are incorporated into the adult brains of a variety of organisms, from humans and higher vertebrates, to non-vertebrates such as crustaceans. In virtually all of these systems serotonergic pathways appear to provide important regulatory influences over the machinery producing the new neurons. We have developed an in vitro preparation where adult neurogenesis can be maintained under highly controlled conditions, and are using this to test the influence of hormones on the production of neurons in the crustacean (Homarus americanus) brain. Serotonin levels have been manipulated in this in vitro preparation, and the resulting effects on the rate of neurogenesis have been documented. In addition we have compared in vitro influences of serotonin with results acquired from in vivo exposure of whole animals to serotonin. These experiments suggest that there are multiple mechanisms and pathways by which serotonin may regulate neurogenesis in the crustacean brain: (1) serotonin is effective in regulating neurogenesis at levels as low as 10−10M, suggesting that circulating serotonin may have hormonal influences on neuronal precursor cells residing in the proliferation zones; (2) contrasting effects of serotonin on neurogenesis (up- vs. down-regulation) at high concentrations (10−4M), dependent upon whether eyestalk tissue is present or absent, indicate that serotonin elicits the release of substances from the sinus glands that are capable of suppressing neurogenesis; (3) previously demonstrated (Beltz et al., 2001) serotonergic fibers from the dorsal giant neuron project directly into the proliferation zone in Cluster 10, suggest synaptic or local influences on neurogenesis in the proliferation zones where the final cell divisions and neuronal differentiation occur. Serotonin therefore regulates neurogenesis by multiple pathways, and the specific mode of influence is concentration-dependent.

Crustacean neuroendocrine systems and their signaling agents

“…As discussed later in this review, hormonally delivered serotonin has recently been implicated in the control of adult neurogenesis within several regions of the crustacean brain ( e.g. Benton et al 2008). …”

“…Initially, Beltz and co-workers observed that the rate of neurogenesis in the lobster Homarus americanus brain decreased when serotonin was pharmacologically depleted using 5,7-dihydroxytryptamine Beltz et al 2001). Later, they demonstrated that the rate of neurogenesis in Homarus americanus was highly dependent on the serotonin concentration, with in vitro application of a low dose of serotonin (10 -10 M) to the brain eliciting a pronounced increase in neurogenesis and application of higher concentrations of serotonin resulting in a dosedependent decrease in neurogenesis (Benton et al 2008;Fig. 12).…”

“…Statistical similarity is indicated by the same letters (n=10 per group for each serotonin concentration and control). Figure and legend used with permission from Benton et al (2008) Fig. 13 Comparison between the levels of serotonin (5-HT) collected in the perfusate over 4 cycles from the brain of the crayfish Cherax destructor during periods of no stimulation (first column) and stimulation (second column) of the cluster 10 cell bodies, as measured by high pressure liquid chromatography.…”

Brain Photoreceptor Pathways Contributing to Circadian Rhythmicity in Crayfish

“…Photoperiodic rhythmicity can be found in locomotory activity, size of the response of compound eye receptor potentials (ERGs), movement of pigment in the eyes and on the body (Aréchiga et al, 1993;FanjulMoles & Pietro-Sagredo, 2003), levels of serotonin in the brain (Benton et al, 2008;Wildt et al, 2003), and rate of neurogenesis in adult animals (Goergen et al, 2002). Many of these rhythms persist in conditions of constant darkness and are therefore under the control of endogenous circadian oscillators (Aréchiga et al, 1993).…”

Olfaction in child and adolescent anorexia nervosa

“…Scatter plots did not indicate an effect of medication on odor identification; at the best in combination with co-morbidity identification is decreased. Although the mechanisms of serotonergic and dopaminergic effects on olfaction are insufficiently explored, one hypothetical mechanism might be pharmacological modulation of neurogenesis in the subventricular zone thus affecting the maturation of neural stem cells in the olfactory bulb into dopaminergic inhibitory interneurons (Benton et al 2008;Borta and Höglinger 2007). On the other hand, psychopharmacologic drugs might also act acutely and directly in the olfactory bulbs.…”