Histamine H₃ Receptors Suppress Synaptic Transmission in the Rat Insular Cortex Supporting the Development of the Gustation

Abstract

Histamine H₃ receptors are autoreceptors that regulate histamine release from histaminergic neuronal terminals. The celebral cortex, including the insular cortex (IC), expresses abundant H₃ receptors; however, the functions and mechanisms of H₃ receptors remain unknown. The aim of this study was to elucidate the functional roles of H₃ receptors in synaptic transmission in the rat IC. Unitary excitatory and inhibitory postsynaptic currents (uEPSCs and uIPSCs) were obtained through paired whole-cell patch-clamp recording in cerebrocortical slice preparations. The H₃ receptor agonist, R-α-methylhistamine (RAMH), reducedthe uEPSCs amplitude. Similarly, RAMH reduced the uIPSC amplitude. JNJ5207852 dihydrochloide or thioperamide, H₃ receptor antagonist, inhibited RAMH-induced suppression of uEPSCs and uIPSCs. Unexpectedly, thioperamide alone increased the uIPSCs amplitude. Miniature EPSC or IPSC recordings support the hypothesis that the activation H₃ receptors suppresses the release of glutamate and GABA from presynaptic terminals. The suppressive regulation of H₃ receptors on synaptic transmission might mediate the regulation of sensory information processes, such as gustation and visceral sensation in the IC.