Regulation of inhibitory synaptic transmission by vasoactive intestinal peptide (VIP) in the mouse suprachiasmatic nucleus. 2003

Jason Itri, and Christopher S Colwell
Mental Retardation Research Center, Department of Psychiatry, University of California, Los Angeles, California 90024-1759, USA.

Circadian rhythmicity in mammals is generated by a pair of nuclei in the anterior hypothalamus known as the suprachiasmatic nuclei (SCN), whose neurons express a variety of neuropeptides that are thought to play an important role in the circadian timing system. To evaluate the influence of VIP on inhibitory synaptic transmission between SCN neurons, we used whole cell patch-clamp recording in an acute brain slice preparation of mouse SCN. Baseline spontaneous GABAergic inhibitory postsynaptic currents (IPSCs) varied significantly between regions and across phases, with a greater frequency of IPSCs observed in the dorsomedial region during the early night. Bath-applied VIP caused a significant increase in the frequency of spontaneous inhibitory postsynaptic currents (sIPSC) in a reversible and dose-dependent manner with no effect on the mean amplitude or kinetic parameters. The effect of VIP was widespread throughout the SCN and observed in both ventrolateral (VL) and dorsomedial (DM) regions. In the presence of tetrodotoxin, VIP increased the frequency of miniature IPSCs without affecting the mean magnitude or kinetic parameters. The magnitude of the enhancement by VIP was significantly larger during the day than during the night. Pretreatment with the VIP-PACAP receptor antagonist [Ac-Tyr1, D-Phe2]-GHRF 1-29 or the selective VPAC2 receptor antagonist PG 99-465 completely blocked the VIP-induced enhancement. The effect of VIP appears to be mediated by a cAMP/PKA-dependent mechanism as forskolin mimics, while the PKA antagonist H-89 blocks the observed enhancement of GABA currents. Our data suggest that VIP activates presynaptic VPAC2 receptors to regulate inhibitory synaptic transmission within the SCN and that this effect varies from day to night.

UI MeSH Term Description Entries
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009433 Neural Inhibition The function of opposing or restraining the excitation of neurons or their target excitable cells. Inhibition, Neural
D009435 Synaptic Transmission The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES. Neural Transmission,Neurotransmission,Transmission, Neural,Transmission, Synaptic
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
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
D013493 Suprachiasmatic Nucleus An ovoid densely packed collection of small cells of the anterior hypothalamus lying close to the midline in a shallow impression of the OPTIC CHIASM. Hypothalamic Suprachiasmatic Nuclei,Hypothalamic Suprachiasmatic Nucleus,Suprachiasmatic Nuclei,Suprachiasmatic Nuclei, Hypothalamic,Suprachiasmatic Nucleus, Hypothalamic
D014660 Vasoactive Intestinal Peptide A highly basic, 28 amino acid neuropeptide released from intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems and is neuroprotective. It binds special receptors (RECEPTORS, VASOACTIVE INTESTINAL PEPTIDE). VIP (Vasoactive Intestinal Peptide),Vasoactive Intestinal Polypeptide,Vasointestinal Peptide,Intestinal Peptide, Vasoactive,Intestinal Polypeptide, Vasoactive,Peptide, Vasoactive Intestinal,Peptide, Vasointestinal,Polypeptide, Vasoactive Intestinal
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D066298 In Vitro Techniques Methods to study reactions or processes taking place in an artificial environment outside the living organism. In Vitro Test,In Vitro Testing,In Vitro Tests,In Vitro as Topic,In Vitro,In Vitro Technique,In Vitro Testings,Technique, In Vitro,Techniques, In Vitro,Test, In Vitro,Testing, In Vitro,Testings, In Vitro,Tests, In Vitro,Vitro Testing, In

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