The Effects of Ghrelin on Spike Activity of the Suprachiasmatic Nucleus Neurones of the Rat

In one of the most important non-photic mechanisms of thecircadian biological clock synchronization of the hypothalamus suprachiasmaticnucleus with environmental geophysical 24 h rhythm, informationon feeding schedule, composition and calorie content of food isused. Hormone ghrelin, a product of the neuroendocrine oxyntic cellsof the gastric mucosa to be a signal molecule within this mechanism.In experiments on sagittal hypothalamic slices of male Wistar rats,the effects of 25 nM ghrelin on spike activity and parameters ofspike information coding were investigated. Application of ghrelininduced an increase in spike frequency and a decrease in entropyof interspike interval distribution in 32.1% of the neurones recorded.In 29.6% of the cells, opposite responses in the form of a reductionof activity and an increase in the entropy of interspike intervaldistribution were observed. Parameters of spike activity of thereminder 38.3% neurones of the suprachiasmatic nucleus did not change.The observed responses of the entropy of interspike interval distributionindicate the appropriate changes in a degree of irregularity ofinterspike interval induced by ghrelin. Application of selectivehigh-affinity antagonist of GHS-R1a receptor, JMV 2959 (100 nM)did not induce responses of the investigated parameters of spikeactivity but completely prevented changes of both, spike frequency andentropy of interspike interval distribution observed in the presenceof ghrelin. The obtained data show that hormone ghrelin by a directinfluence on the suprachiasmatic nucleus in vitro modulates the activitylevel and spike code of relatively numerous population of neuronesof the nucleus, wherein the effects of ghrelin are mediated by GHS-R1areceptors. The results of the current study provide additional evidencein favour of the hypothesis on the involvement of ghrelin in mechanismsof non-photic entrainment of the circadian biological clock in accordancewith severity of food motivation and level of metabolism.