Serotonin Attenuates Feedback Excitation onto O-LM Interneurons

Cereb Cortex. 2015 Nov;25(11):4572-83. doi: 10.1093/cercor/bhv098. Epub 2015 May 28.

Abstract

The serotonergic system is a subcortical neuromodulatory center that controls cortical information processing in a state-dependent manner. In the hippocampus, serotonin (5-HT) is released by ascending serotonergic fibers from the midbrain raphe nuclei, thereby mediating numerous modulatory functions on various neuronal subtypes. Here, we focus on the neuromodulatory effects of 5-HT on GABAergic inhibitory oriens lacunosum-moleculare (O-LM) cells in the hippocampal area CA1 of the rat. These interneurons are thought to receive primarily local excitatory input and are, via their axonal projections to stratum lacunosum-moleculare, ideally suited to control entorhinal cortex input. We show that 5-HT reduces excitatory glutamatergic transmission onto O-LM interneurons. By means of paired recordings from synaptically connected CA1 pyramidal cells and O-LM interneurons we reveal that this synapse is modulated by 5-HT. Furthermore, we demonstrate that the reduction of glutamatergic transmission by serotonin is likely to be mediated via a decrease of calcium influx into presynaptic terminals of CA1 pyramidal cells. This modulation of excitatory synaptic transmission onto O-LM interneurons by 5-HT might be a mechanism to vary the activation of O-LM interneurons during ongoing network activity and serve as a brain state-dependent switch gating the efficiency of entorhinal cortex input to CA1 pyramidal neurons.

Keywords: 5-HT; CA1; paired recordings; presynaptic neuromodulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • CA1 Region, Hippocampal / cytology*
  • Cadmium Chloride / pharmacology
  • Calcium / metabolism
  • Calcium Channel Blockers
  • Dose-Response Relationship, Drug
  • Electric Stimulation
  • Entorhinal Cortex / cytology
  • Entorhinal Cortex / physiology*
  • Excitatory Postsynaptic Potentials / drug effects*
  • Feedback, Physiological / drug effects*
  • GABA Agents / pharmacology
  • GABAergic Neurons / drug effects*
  • Glutamic Acid / pharmacology
  • In Vitro Techniques
  • Patch-Clamp Techniques
  • Rats
  • Rats, Wistar
  • Serotonin / pharmacology*
  • Serotonin Agents / pharmacology

Substances

  • Calcium Channel Blockers
  • GABA Agents
  • Serotonin Agents
  • Serotonin
  • Glutamic Acid
  • Cadmium Chloride
  • Calcium