5HT1B receptor-mediated pre-synaptic depression of excitatory inputs to the rat lateral habenula

Eun Kyung Hwang, Jun Mo Chung

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Accumulating lines of evidence indicate that the lateral habenula (LHb), which reciprocally interacts with raphe nuclei (RN), displays hyperactivity including synaptic potentiation of excitatory inputs to the LHb during a depressed state. Despite the potential importance of glutamatergic excitatory synapses in depression-like behavior, modulation of these LHb synapses by monoamines such as serotonin (5HT) is not fully understood at the cellular and molecular level. Therefore, we used whole cell voltage-clamp recording to examine the molecular mechanisms by which 5HT modulates glutamatergic transmission in the LHb. The present study provides the first evidence that glutamatergic transmission of LHb synapses is inhibited by activation of the 5HT1B receptor at the pre-synapse in both acute depression (5HT-AD) and long-term depression (5HT-LTD). We further show that 5HT-AD results from the activation of Shaker-type K+ channels whereas 5HT-LTD depends on inhibition of the adenylyl cyclase-cAMP (AC-cAMP) pathway with an increase in pre-synaptic Ca2+ release from ryanodine-sensitive internal stores in an NO-dependent manner.

Original languageEnglish
Pages (from-to)153-165
Number of pages13
StatePublished - Jun 2014

Bibliographical note

Funding Information:
An SBIE grant from GIST , an NRF grant from KMEST ( 2010-0008120 ), and an EWU GT5 grant in 2013 to JMC supported this work.


  • EPSCs
  • Epithalamus
  • Patch clamp
  • Serotonin
  • Synaptic plasticity


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