The cerebellar fastigial nucleus (FN), together with the interpositus nucleus (IN), constitutes the two ﬁnal output nuclei of the spinocerebellum and plays an important role in body and limb movements. Previous studies have revealed a direct histaminergic projection from the hypothalamus to the cerebellar nuclei and an excitatory effect of histamine on the IN neurons. However, role of hypothalamic histaminergic projection in the FN has been still little known. Here we show that histamine elicited the FN neurons of rats a concentration-dependent excitatory response in vitro. The histamine-induced excitation on FN neurons was mediated by postsynaptic histamine H2 rather than H1 receptors. In behavioral tests, microinjection of histamine into bilateral FNs remarkably improved motor performances of rats on both accelerating rota-rod and balance beam. Selective H2 receptor antagonist ranitidine considerably declined thosemotor performances and selective H2 receptor agonist dimaprit mimicked the facilitation effect of histamine on themovements. But selective H1 receptor antagonisttriprolidine and agonist 2-pyridylethylamine had no effect. Furthermore, microinjection of histamine into bilateral FNs narrowed stride width of footprint but did notinﬂuence wire suspension, whereas microinjection of histamine into bilateral INs increased stride length and promoted suspension. These results demonstrate that histamine enhances rat motor balance and coordination through modulation of both proximal and distal muscles by activation of histamine H2 receptors in the cerebellar FN and IN, and suggest that the hypothalamocerebellar histaminergic projections may modulate the ﬁnal outputs of the spinocerebellum and participate in the cerebellum mediated motor control.
The presentation was simple and clear.
Some interesting thoughts that arose from the presentation:
- Are TMN neurons exclusively histaminergic?
- Do local drug microinjection techniques account for the possibility of its diffusion into circulation?
- Is Foot print measure a valid tool for gait assessment in rodents?
- Do long term 'Ranitidine' users need to worry about their motor performance?