Presynaptic inhibition by 5-HT1B receptors of glutamatergic synaptic inputs onto serotonergic caudal raphe neurones in rat. 1998

Y W Li, and D A Bayliss
Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.

1. Autonomous, pacemaker-like activity of serotonergic raphe neurones and its autoregulation by somatodendritic 5-HT1A receptors are well described, but little is known of synaptic inputs onto raphe neurones or their modulation. Therefore, we recorded unitary excitatory postsynaptic currents (EPSCs) in caudal raphe neurones (raphe obscurus and pallidus) following local electrical stimulation in a neonatal rat brainstem slice preparation; most neurones (79 %; n = 72/91) recovered following post hoc immunohistochemistry were tryptophan hydroxylase-immunoreactive, indicating that they were serotonergic. 2. Evoked EPSCs occurred at relatively constant latency with variable amplitude and apparent 'failures' at fixed suprathreshold stimulus intensity. At -60 mV, EPSCs were wholly due to CNQX-sensitive, non-NMDA glutamate receptors; at depolarized potentials, a small AP-5-sensitive NMDA component was often observed. 3. EPSCs were potently and reversibly inhibited by 5-HT with an EC50 of 0.1 microM. This effect was mimicked by 5-HT1B agonists (CP-93,129 and anpirtoline), but not by a 5-HT1A agonist (8-OH-DPAT), indicating that 5-HT1B receptors mediate the inhibition of EPSCs. 4. Multiple lines of evidence indicate that inhibition of EPSCs by 5-HT was mediated presynaptically. First, currents evoked by exogenous glutamate application were unaffected by 5-HT and/or 5-HT1B agonists. In addition, the frequency of spontaneous glutamatergic miniature EPSCs was diminished by CP-93,129 and paired-pulse facilitation of EPSCs was enhanced by 5-HT. Finally, the 5-HT1B receptor agonists that blocked synaptic transmission had no effect on resting membrane properties of raphe neurones. 5. These data indicate that serotonergic caudal raphe neurones receive glutamatergic inputs that are inhibited by presynaptic 5-HT1B receptors; inhibition of excitatory synapses onto raphe cells may represent a novel mechanism for autoregulation of serotonergic neuronal activity by 5-HT.

UI MeSH Term Description Entries
D009433 Neural Inhibition The function of opposing or restraining the excitation of neurons or their target excitable cells. Inhibition, Neural
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D011903 Raphe Nuclei Collections of small neurons centrally scattered among many fibers from the level of the TROCHLEAR NUCLEUS in the midbrain to the hypoglossal area in the MEDULLA OBLONGATA. Caudal Linear Nucleus of the Raphe,Interfascicular Nucleus,Nucleus Incertus,Rostral Linear Nucleus of Raphe,Rostral Linear Nucleus of the Raphe,Superior Central Nucleus,Central Nucleus, Superior,Incertus, Nucleus,Nuclei, Raphe,Nucleus, Interfascicular,Nucleus, Raphe,Nucleus, Superior Central,Raphe Nucleus
D011985 Receptors, Serotonin Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. 5-HT Receptor,5-HT Receptors,5-Hydroxytryptamine Receptor,5-Hydroxytryptamine Receptors,Receptors, Tryptamine,Serotonin Receptor,Serotonin Receptors,Tryptamine Receptor,Tryptamine Receptors,Receptors, 5-HT,Receptors, 5-Hydroxytryptamine,5 HT Receptor,5 HT Receptors,5 Hydroxytryptamine Receptor,5 Hydroxytryptamine Receptors,Receptor, 5-HT,Receptor, 5-Hydroxytryptamine,Receptor, Serotonin,Receptor, Tryptamine,Receptors, 5 HT,Receptors, 5 Hydroxytryptamine
D005071 Evoked Potentials Electrical responses recorded from nerve, muscle, SENSORY RECEPTOR, or area of the CENTRAL NERVOUS SYSTEM following stimulation. They range from less than a microvolt to several microvolts. The evoked potential can be auditory (EVOKED POTENTIALS, AUDITORY), somatosensory (EVOKED POTENTIALS, SOMATOSENSORY), visual (EVOKED POTENTIALS, VISUAL), or motor (EVOKED POTENTIALS, MOTOR), or other modalities that have been reported. Event Related Potential,Event-Related Potentials,Evoked Potential,N100 Evoked Potential,P50 Evoked Potential,N1 Wave,N100 Evoked Potentials,N2 Wave,N200 Evoked Potentials,N3 Wave,N300 Evoked Potentials,N4 Wave,N400 Evoked Potentials,P2 Wave,P200 Evoked Potentials,P50 Evoked Potentials,P50 Wave,P600 Evoked Potentials,Potentials, Event-Related,Event Related Potentials,Event-Related Potential,Evoked Potential, N100,Evoked Potential, N200,Evoked Potential, N300,Evoked Potential, N400,Evoked Potential, P200,Evoked Potential, P50,Evoked Potential, P600,Evoked Potentials, N100,Evoked Potentials, N200,Evoked Potentials, N300,Evoked Potentials, N400,Evoked Potentials, P200,Evoked Potentials, P50,Evoked Potentials, P600,N1 Waves,N2 Waves,N200 Evoked Potential,N3 Waves,N300 Evoked Potential,N4 Waves,N400 Evoked Potential,P2 Waves,P200 Evoked Potential,P50 Waves,P600 Evoked Potential,Potential, Event Related,Potential, Event-Related,Potential, Evoked,Potentials, Event Related,Potentials, Evoked,Potentials, N400 Evoked,Related Potential, Event,Related Potentials, Event,Wave, N1,Wave, N2,Wave, N3,Wave, N4,Wave, P2,Wave, P50,Waves, N1,Waves, N2,Waves, N3,Waves, N4,Waves, P2,Waves, P50
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012701 Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator. 5-HT,5-Hydroxytryptamine,3-(2-Aminoethyl)-1H-indol-5-ol,Enteramine,Hippophaine,Hydroxytryptamine,5 Hydroxytryptamine
D013569 Synapses Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions. Synapse
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D017366 Serotonin Receptor Agonists Endogenous compounds and drugs that bind to and activate SEROTONIN RECEPTORS. Many serotonin receptor agonists are used as ANTIDEPRESSANTS; ANXIOLYTICS; and in the treatment of MIGRAINE DISORDERS. 5-HT Agonists,5-Hydroxytryptamine Agonists,Serotonin Agonists,5-HT Agonist,5-Hydroxytrytamine Agonist,Receptor Agonists, Serotonin,Serotonergic Agonist,Serotonergic Agonists,Serotonin Agonist,Serotonin Receptor Agonist,5 HT Agonist,5 HT Agonists,5 Hydroxytryptamine Agonists,5 Hydroxytrytamine Agonist,Agonist, 5-HT,Agonist, 5-Hydroxytrytamine,Agonist, Serotonergic,Agonist, Serotonin,Agonist, Serotonin Receptor,Agonists, 5-HT,Agonists, 5-Hydroxytryptamine,Agonists, Serotonergic,Agonists, Serotonin,Agonists, Serotonin Receptor,Receptor Agonist, Serotonin

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