Histamine excites rat spinalα-motoneurons and the underlying mechanisms

【摘要】：正The central histaminergic nervous system originates from the tuberomammillary nucleus of the hypothalamus and widely innervates almost the whole brain including the spinal cord.Although series of studies from our and other laboratories have demonstrated that the system modulates various subcortical motor structures in the brain,the effect of histamine on the spinalα-motoneuron,the final common path for motor control,has still been unknown.In this study,the immunofluorescence staining results showed that both histamine H_1 and H_2 receptors are present in spinalα-motoneurons in adult rats.Using 8- to 14-day-old rat spinal slice preparations and intracellular recordings in current-clamp mode,the effect of histamine on theα-motoneurons in lumbar spinal cord and the underlying mechanism were further studied.Spinalα-motoneurons were identified by both applying antidromic activation and labeling with Lucifer Yellow.Bath application of histamine(1-1000μmol/L) induced a membrane depolarization in the majority of recorded spinalα-motoneurons(78/90,86%).Perfusing slices with tetrodotoxin or low-Ca~(2+)/high-Mg~(2+) medium did not block the histamine-induced excitation(n=10),indicating a direct postsynaptic action of histamine on the motoneurons.Our results further showed that histamine excites spinal a-motoneurons of neonatal rat via both histamine H_1 and H_2 receptors.The histamine H_1 receptor-mediated spinal motoneurons excitation is coupled with the blockage of leak K~+ channels and activation of Na~+-Ca~(2+) exchangers,whereas H_1 receptor-mediated excitation is coupled with I_h channels.Thus,we suggest that the histaminergic fibers originating from the hypothalamus may directly modulate final motor outputs through their excitatory innervations on spinalα-motoneuron and actively regulate on-going motor execution and spinal cord-mediated motor reflexes.