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  • Local potentiation of excitatory synapses by serotonin and its alteration in rodent models of depression.

Local potentiation of excitatory synapses by serotonin and its alteration in rodent models of depression.

Nature neuroscience (2013-03-19)
Xiang Cai, Angy J Kallarackal, Mark D Kvarta, Sasha Goluskin, Kaitlin Gaylor, Aileen M Bailey, Hey-Kyoung Lee, Richard L Huganir, Scott M Thompson
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Glutamate Receptor 1 Antibody, phosphoSer 845, Chemicon®, from rabbit
Sigma-Aldrich
Anti-Serotonin Antibody, serum, Chemicon®
Sigma-Aldrich
Anti-phospho-AMPA Receptor, GluR1 Subunit (pSer831) antibody produced in rabbit, ~1 mg/mL, affinity isolated antibody, buffered aqueous solution