title: Local potentiation of excitatory synapses by serotonin and its alteration in rodent models of depression.
abstract: The causes of major depression remain unknown. Antidepressants elevate concentrations of monoamines, particularly serotonin, but it remains uncertain which downstream events are critical to their therapeutic effects. We found that endogenous serotonin selectively potentiated excitatory synapses formed by the temporoammonic pathway with CA1 pyramidal cells via activation of serotonin receptors (5-HT(1B)Rs), without affecting nearby Schaffer collateral synapses. This potentiation was expressed postsynaptically by AMPA-type glutamate receptors and required calmodulin-dependent protein kinase-mediated phosphorylation of GluA1 subunits. Because they share common expression mechanisms, long-term potentiation and serotonin-induced potentiation occluded each other. Long-term consolidation of spatial learning, a function of temporoammonic-CA1 synapses, was enhanced by 5-HT(1B)R antagonists. Serotonin-induced potentiation was quantitatively and qualitatively altered in a rat model of depression, restored by chronic antidepressants, and required for the ability of chronic antidepressants to reverse stress-induced anhedonia. Changes in serotonin-mediated potentiation, and its recovery by antidepressants, implicate excitatory synapses as a locus of plasticity in depression.
authors.affiliation: Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Cai
authors.forename: Angy J
authors.initials: AJ
authors.lastname: Kallarackal
authors.forename: Mark D
authors.initials: MD
authors.lastname: Kvarta
authors.forename: Sasha
authors.initials: S
authors.lastname: Goluskin
authors.forename: Kaitlin
authors.initials: K
authors.lastname: Gaylor
authors.forename: Aileen M
authors.initials: AM
authors.lastname: Bailey
authors.forename: Hey-Kyoung
authors.initials: HK
authors.lastname: Lee
authors.forename: Richard L
authors.initials: RL
authors.lastname: Huganir
authors.forename: Scott M
authors.initials: SM
authors.lastname: Thompson
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy / Q000378:metabolism*; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000172:deficiency / Q000502:physiology*; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000928:Antidepressive Agents; D058829:Serotonin 5-HT1 Receptor Antagonists; D012701:Serotonin