title: 5HT(1B) receptor-mediated pre-synaptic depression of excitatory inputs to the rat lateral habenula.
abstract: 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 5HT(1B) 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 Ca(2+) release from ryanodine-sensitive internal stores in an NO-dependent manner.
authors: Department of Brain and Cognitive Sciences, Brain Disease Research Institute, Ewha Womans University, Seoul, Republic of Korea.
authors: Eun-Kyung
authors: EK
authors: Hwang
authors: Department of Brain and Cognitive Sciences, Brain Disease Research Institute, Ewha Womans University, Seoul, Republic of Korea. Electronic address: jmchung@ewha.ac.kr.
authors: Jun-mo
authors: JM
authors: Chung
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D019262:Habenula / Q000166:cytology* / Q000187:drug effects; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D018490:Serotonin Agents / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D044302:Receptor, Serotonin, 5-HT1B; D018490:Serotonin Agents; D012701:Serotonin; D000242:Cyclic AMP
keywords: EPSCs; Epithalamus; Patch clamp; Serotonin; Synaptic plasticity