5-HT2A receptor-mediated excitation on cerebellar fastigial nucleus neurons and promotion of motor behaviors in rats

Abstract

It has long been known that serotonergic afferent inputs are the third largest afferent population in the cerebellum after mossy fibers and climbing fibers. However, the role of serotonergic inputs in cerebellar-mediated motor behaviors is still largely unknown. Here, we show that only 5-HT2A receptors among the 5-HT2 receptor subfamily are expressed and localized in the rat cerebellar fastigial nucleus (FN), one of the ultimate outputs of the spinocerebellum precisely regulating trunk and limb movements. Remarkably, selective activation of 5-HT2A receptors evokes a postsynaptic excitatory effect on FN neurons in a concentration-dependent manner in vitro, which is in accord with the 5-HT-elicited excitation on the same tested neurons. Furthermore, selective 5-HT2A receptor antagonist M100907 concentration-dependently blocks the excitatory effects of 5-HT and TCB-2, a 5-HT2A receptor agonist, on FN neurons. Consequently, microinjection of 5-HT into bilateral FNs significantly promotes rat motor performances on accelerating rota-rod and balance beam and narrows stride width rather than stride length in locomotion gait. All these motor behavioral effects are highly consistent with those of selective activation of 5-HT2A receptors in FNs, and blockage of the component of 5-HT2A receptor-mediated endogenous serotonergic inputs in FNs markedly attenuates these motor performances. All these results demonstrate that postsynaptic 5-HT2A receptors greatly contribute to the 5-HT-mediated excitatory effect on cerebellar FN neurons and promotion of the FN-related motor behaviors, suggesting that serotonergic afferent inputs may actively participate in cerebellar motor control through their direct modulation on the final output of the spinocerebellum.

Selective Modulation of Histaminergic Inputs on Projection Neurons of Cerebellum Rapidly Promotes Motor Coordination via HCN Channels

“…Balance beam tests have been widely used to assess motor balance and coordination of rodents [2,14,15,28]. The balance beam was a rod of 190 cm in length and a diameter of 2.5 cm.…”

Role of Corticotropin-Releasing Factor in Cerebellar Motor Control and Ataxia

“…The rats were allowed to freely traverse a clear plexiglass tunnel (100 cm 3 10 cm 3 10 cm), with a sheet of white absorbent paper (100 cm 3 10 cm) placed at the bottom of the track and a darkened cage at the end. The resulting tracks provide the spatial relationship of consecutive footfalls from which the stride length and width were measured as previously described [18,59].…”

Histamine Increases Neuronal Excitability and Sensitivity of the Lateral Vestibular Nucleus and Promotes Motor Behaviors via HCN Channel Coupled to H2 Receptor

“…We used accelerating rota-rod test to assess vestibular-related motor balance and coordination (Song et al, 2006; Zhang et al, 2011, 2014; He et al, 2012). Animals were placed on the rota-rod (Ugo Basile, Varese, Italy) and habituated to low rotation (4 rpm) for 30 s first.…”

“…We also employed balance beam test to evaluate vestibular motor function (Song et al, 2006; Zhang et al, 2011, 2014; He et al, 2012). The balance beam (2.5 cm in diameter) was 190 cm in length.…”