Abstract
Serotoninergic transmission is implicated in the photic and non-photic regulation of circadian rhythms. 5-HT (1–100 μM), carboxamidotryptamine (5-CT 0.1–10 μM) and (+)-8-hydroxy-dipropylaminotetraline (8-OH-DPAT, 1–30 μM) dose-dependently activated an outward current (5–100 pA) in 30% of neurons voltage-clamped at −60 mV in the suprachiasmatic nucleus (SCN) in vitro slice. EC 50 values were 7.0 μM for 5-HT and 0.2 μM for 5-CT. Serotonin-induced outward current was associated with an increase in input conductance, and the current was blocked by Ba 2+ (1 mM). The amplitude of the current was enhanced by depolarization, reduced by hyperpolarization, and reversed its polarity during a hyperpolarization beyond the potassium equilibrium potential. Mean amplitudes of the 5-HT outward current changed with time of the subjective circadian day. The value near CT2 (23.8 pA) was about 4 times greater than that around CT14 (6.7 pA). Cells that responded with an outward current showed four types of morphology: monopolar, simple bipolar, curly bipolar and radial shaped; they were localized in all parts of the SCN. The EPSC evoked by retino-hypothalamic-tract (RHT) stimulation was inhibited 26% but the inward current induced by exogenously applied glutamate or NMDA was not affected by serotonin agonists. Focal stimulation-induced and spontaneous IPSC but not the exogenous GABA-induced outward current were inhibited by 5-HT agonists in a subpopulation of cells. In conclusion, 5-HT regulates SCN neurons by both pre- and post-synaptic inhibitory mechanisms; the latter may play a key role in modulating SCN circadian rhythm by activation of 5-HT receptors and opening of a potassium channel.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.