title: Action potential-independent and pharmacologically unique vesicular serotonin release from dendrites.
abstract: Serotonin released within the dorsal raphe nucleus (DR) induces feedback inhibition of serotonin neuron activity and consequently regulates mood-controlling serotonin release throughout the forebrain. Serotonin packaged in vesicles is released in response to action potentials by the serotonin neuron soma and terminals, but the potential for release by dendrites is unknown. Here, three-photon microscopy imaging of endogenous serotonin in living rat brain slice, immunofluorescence, and immunogold electron microscopy detection of VMAT2 (vesicular monoamine transporter 2) establish the presence of vesicular serotonin within DR dendrites. Furthermore, activation of glutamate receptors is shown to induce vesicular serotonin release from dendrites. However, unlike release from the soma and terminals, dendritic serotonin release is independent of action potentials, relies on L-type Ca(2+) channels, is induced preferentially by NMDA, and displays distinct sensitivity to the selective serotonin reuptake inhibitor (SSRI) antidepressant fluoxetine. The unique control of dendritic serotonin release has important implications for DR physiology and the antidepressant action of SSRIs, dihydropyridines, and NMDA receptor antagonists.
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Colgan
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Cavolo
authors.forename: Kathryn G
authors.initials: KG
authors.lastname: Commons
authors.forename: Edwin S
authors.initials: ES
authors.lastname: Levitan
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism; D003712:Dendrites / Q000187:drug effects / Q000502:physiology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D022142:Secretory Vesicles / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism
chemical_list: D020746:Calcium Channels, L-Type; D018690:Excitatory Amino Acid Agonists; D005473:Fluoxetine; D016202:N-Methylaspartate; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D050493:Vesicular Monoamine Transport Proteins; C493454:Slc18a2 protein, rat