Excitatory effect of histamine on neuronal activity of rat cerebellar fastigial nucleus in vitro

Abstract

The cerebellar fastigial nucleus (FN) holds an important role in motor control and body balance. Previous studies have revealed that the nucleus is innervated by direct hypothalamocerebellar histaminergic fibers. However, the functional role of histaminergic projection in cerebellar FN has never been established. In this study, we investigated the effect of histamine on neuronal firing of cerebellar FN by using slice preparations. Sixty-five FN cells were recorded from 47 cerebellar slices, and a vast majority of the cells responded to histamine stimulation with an excitatory response (58/65, 89.2%). Perfusing slices with low-Ca 2+ /high-Mg 2+ medium did not block the histamine-induced excitation (n=10), supporting a direct postsynaptic action of histamine on the cells. Furthermore, the excitatory effect of histamine on FN neurons was not blocked by selective histamine H 1 receptor antagonist triprolidine (n=15) or chlorpheniramine (n=10), but was effectively suppressed by ranitidine (n=15), a highly selective histamine H 2 receptor antagonist. On the other hand, highly selective histamine H 2 receptor agonist dimaprit (n=20) instead of histamine H 1 receptor agonist 2-pyridylethylamine (n=16) mimicked the excitatory effect of histamine on FN neurons. The dimaprit-induced FN neuronal excitation was effectively antagonized by selective histamine H 2 receptor antagonist ranitidine (n=13) but not influenced by selective histamine H 1 receptor antagonist triprolidine (n=15). These results demonstrate that histamine excites cerebellar FN cells via the histamine H 2 receptor mechanism and suggest that the hypothalamocerebellar histaminergic fibers may modulate cerebellar FN-mediated sensorimotor integration through their excitatory innervations on FN neurons. histamine, histamine receptors, cerebellar fastigial nucleus, hypothalamocerebellar histaminergic projectionsThe central histaminergic nervous system originates from the tuberomammillary nucleus of the hypothalamus and widely innervates almost the whole brain including the cerebellum [1][2][3] . Immunohistochemical studies have offered convincing evidence that the histaminecontaining neurons project from the tuberomammillary nucleus to both cortex and nuclei of the cerebellum [4,5] . Autoradiographic mapping, immunohistochemical analysis and in situ hybridization experiments have indicated the presence of histamine H 1 , H 2 and H 3 receptors in rat cerebellar cortex and deep cerebellar nuclei [6][7][8][9][10][11][12] . All of these studies reveal the existence of the direct histaminergic pathway between hypothalamus and cerebellum [13] . Our previous studies demonstrated that histamine exerted an excitatory effect on cerebellar cortical granule cells and Purkinje cells, as well as cerebellar interpositus nuclear cells via the mediation of H 2 and/or H 1 receptors [14][15][16] . These findings provide substantial physiological evidence of the existence of histaminergic neurotransmissions in the cerebellum, sug-

Excitatory effect of histamine on rat spinal motoneurons by activation of both H1 and H2 receptors in vitro

“…Actually, histamine actively participates in the regulation of many basic body functions, including the sleep‐waking cycle, energy and endocrine homeostasis, synaptic plasticity, learning, and motor control (Brown et al,2001; Haas and Panula,2003; Zhu et al,2006; Haas et al,2008). In the brain, neurons in several important subcortical motor structures, including the cerebellum (Li et al,1999; Tian et al,2000; Shen et al,2002; Tang et al,2007), basal ganglia (Korotkova et al,2002; Chen et al,2005; Zhou et al,2006), vestibular nuclei (Wang and Dutia,1995; Zhang et al,2008), and red nucleus (Chen et al,2003), are uniformly excited by histamine. Here we report that histamine not only excites spinal motoneurons but also potentiates their repetitive firing behavior via a parallel leftward shift of the f‐I relationship (Fig.…”

“…This suggests that histamine may modulate neuronal activity in these motor structures and participate in motor control. Although a series of studies from our laboratory and other laboratories have already demonstrated an excitatory action of histamine on several subcortical motor structures, such as the cerebellum (Li et al,1999; Tian et al,2000; Shen et al,2002; Tang et al,2007), basal ganglia (Korotkova et al,2002; Chen et al,2005; Zhou et al,2006), vestibular nuclei (Wang and Dutia,1995; Zhang et al,2008), and red nucleus (Chen et al,2003), the effect of histamine on spinal motoneurons, the final common path for all signals from the central nervous system and the spinal intrinsic circuits to skeletal muscles, remains enigmatic.…”