Molecular Neurobiology

, Volume 26, Issue 2–3, pp 203–216

Regulation of GABAergic inhibition by serotonin signaling in prefrontal cortex

Molecular mechanisms and functional implications

DOI: 10.1385/MN:26:2-3:203

Cite this article as:
Yan, Z. Mol Neurobiol (2002) 26: 203. doi:10.1385/MN:26:2-3:203


Serotonergic neurotransmission in prefrontal cortex (PFC) plays a key role in regulating emotion and cognition under normal and pathological conditios. Increasing evidence suggests that serotonin receptors are involved in the complex regulation of GABAergic inhibitory transmission in PFC. Activation of postsynaptic 5-HT2 receptors in PFC pyramidal neurons inhibits GABAA-receptor currents via phosphorylation of GABAA receptor γ2 subunits by RACK1-anchored PKC. In contrast, activation of postsynaptic 5-HT4 receptors produces an activity-dependent bi-directional regulation of GABA-evoked currents in PFC pyramidal neurons, which is mediated through phosphorylation of GABAA-receptor β subunits by anchored PKA. On the presynaptic side, GABAergic inhibition is regulated by 5-HT through the activation of 5-HT2, 5-HT1, and 5-HT3 receptors on GABAergic intereneurons. These data provide a molecular and cellular mechanism for serotonin to dynamically regulate synaptic transmission and neuronal excitability in the PFC network, which may underlie the actions of many antidepressant and antipsychotic drugs.

Index Entries

Serotonin receptors prefrontal cortex GABAA receptors inhibitory synaptic transmission PKC RACK1 PKA AKAP modulation 

Copyright information

© Humana Press Inc 2002

Authors and Affiliations

  1. 1.Department of Physiology and BiophysicsState University of New York at BuffaloBuffalo

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