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Histaminergic afferent system in the cerebellum: structure and function.

Li B, Zhu JN, Wang JJ - Cerebellum Ataxias (2014)

Bottom Line: Histamine receptors, belonging to the family of G protein-coupled receptors, are widely present in the cerebellum.In this way, the histaminergic afferent system actively participates in the cerebellum-mediated motor balance and coordination and nonsomatic functions.On the other hand, considering the hypothalamus is a high regulatory center for autonomic and visceral activities, the hypothalamocerebellar histaminergic fibers/projections, bridging the nonsomatic center to somatic structure, may play a critical role in the somatic-nonsomatic integration.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Science and Technology and State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Mailbox 426, 22 Hankou Road, Nanjing, 210093 China.

ABSTRACT
Histaminergic afferent system of the cerebellum, having been considered as an essential component of the direct hypothalamocerebellar circuits, originates from the tuberomammillary nucleus in the hypothalamus. Unlike the mossy fibers and climbing fibers, the histaminergic afferent fibers, a third type of cerebellar afferents, extend fine varicose fibers throughout the cerebellar cortex and nuclei. Histamine receptors, belonging to the family of G protein-coupled receptors, are widely present in the cerebellum. Through these histamine receptors, histamine directly excites Purkinje cells and granule cells in the cerebellar cortex, as well as the cerebellar nuclear neurons. Therefore, the histaminergic afferents parallelly modulate these dominant components in the cerebellar circuitry and consequently influence the final output of the cerebellum. In this way, the histaminergic afferent system actively participates in the cerebellum-mediated motor balance and coordination and nonsomatic functions. Accordingly, histaminergic reagents may become potential drugs for clinical treatment of cerebellar ataxia and other cerebellar disease. On the other hand, considering the hypothalamus is a high regulatory center for autonomic and visceral activities, the hypothalamocerebellar histaminergic fibers/projections, bridging the nonsomatic center to somatic structure, may play a critical role in the somatic-nonsomatic integration.

No MeSH data available.


Related in: MedlinePlus

Histamine promotes motor balance and motor coordination in accelerating rota-rod via H2 receptors in the cerebellar interpositus nuclei. (A) Motor performances of rats microinjected with normal saline, GABA, histamine, ranitidine (antagonist for H2 receptor) and triprolidine (antagonist for H1 receptor) in accelerating rota-rod. (B) Reversal effect of histamine on ranitidine-injected rats. *P < 0.05; **P < 0.01. Modified from Song et al., Neuroscience, 140:33–43, 2006.
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Fig2: Histamine promotes motor balance and motor coordination in accelerating rota-rod via H2 receptors in the cerebellar interpositus nuclei. (A) Motor performances of rats microinjected with normal saline, GABA, histamine, ranitidine (antagonist for H2 receptor) and triprolidine (antagonist for H1 receptor) in accelerating rota-rod. (B) Reversal effect of histamine on ranitidine-injected rats. *P < 0.05; **P < 0.01. Modified from Song et al., Neuroscience, 140:33–43, 2006.

Mentions: The central histaminergic nervous system has been implicated in many nonsomatic basic physiological functions, such as sleep-waking cycle, energy and endocrine homeostasis, synaptic plasticity, and learning [14–16]. Recently, role of histamine and histaminergic system in somatic motor control receives increasing attention. Intraventricular administration of histamine produced a biphasic effect in spontaneous locomotor activity with an initial transient hypoactivity followed by hyperactivity [86, 87]. Depletion of brain histamine or knockout of histamine receptors influenced motor behaviors [88–90]. The activity levels, such as wheel-running and spontaneous locomotion, in the HDC knock-out mice were lower than those in the wild types [91]. Knockout of H1 receptors in mice altered ambulatory activity and reduced exploratory behavior [89]. The H3 receptor-deficient mice showed a decrease in overall locomotion, wheel-running behavior, and stereotypic responses [90]. Interestingly, bilateral microinjection of histamine into the cerebellar FNs or INs, two final output nuclei of the spinocerebellum, does not influence overground locomotion in rats in an open field [58, 61]. However, microinjection of histamine into the FNs and INs significantly lengthens the endurance time of rats on an accelerating rota-rod (Figure 2) and shortens the time that rats spend traversing a balance beam, which is mediated by H2 receptors [58, 61], indicating a promotion of histamine on cerebellum-mediated motor balance and motor coordination. Furthermore, microinjection of histamine into bilateral FNs narrowed stride width of footprint but did not influence wire suspension, whereas microinjection of histamine into bilateral INs increased stride length and promoted suspension [58] (Figure 3), suggesting that cerebellar histaminergic afferent system may precisely modulate trunk, proximal and distal muscles via biasing the FN and IN.Figure 2


Histaminergic afferent system in the cerebellum: structure and function.

Li B, Zhu JN, Wang JJ - Cerebellum Ataxias (2014)

Histamine promotes motor balance and motor coordination in accelerating rota-rod via H2 receptors in the cerebellar interpositus nuclei. (A) Motor performances of rats microinjected with normal saline, GABA, histamine, ranitidine (antagonist for H2 receptor) and triprolidine (antagonist for H1 receptor) in accelerating rota-rod. (B) Reversal effect of histamine on ranitidine-injected rats. *P < 0.05; **P < 0.01. Modified from Song et al., Neuroscience, 140:33–43, 2006.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4549136&req=5

Fig2: Histamine promotes motor balance and motor coordination in accelerating rota-rod via H2 receptors in the cerebellar interpositus nuclei. (A) Motor performances of rats microinjected with normal saline, GABA, histamine, ranitidine (antagonist for H2 receptor) and triprolidine (antagonist for H1 receptor) in accelerating rota-rod. (B) Reversal effect of histamine on ranitidine-injected rats. *P < 0.05; **P < 0.01. Modified from Song et al., Neuroscience, 140:33–43, 2006.
Mentions: The central histaminergic nervous system has been implicated in many nonsomatic basic physiological functions, such as sleep-waking cycle, energy and endocrine homeostasis, synaptic plasticity, and learning [14–16]. Recently, role of histamine and histaminergic system in somatic motor control receives increasing attention. Intraventricular administration of histamine produced a biphasic effect in spontaneous locomotor activity with an initial transient hypoactivity followed by hyperactivity [86, 87]. Depletion of brain histamine or knockout of histamine receptors influenced motor behaviors [88–90]. The activity levels, such as wheel-running and spontaneous locomotion, in the HDC knock-out mice were lower than those in the wild types [91]. Knockout of H1 receptors in mice altered ambulatory activity and reduced exploratory behavior [89]. The H3 receptor-deficient mice showed a decrease in overall locomotion, wheel-running behavior, and stereotypic responses [90]. Interestingly, bilateral microinjection of histamine into the cerebellar FNs or INs, two final output nuclei of the spinocerebellum, does not influence overground locomotion in rats in an open field [58, 61]. However, microinjection of histamine into the FNs and INs significantly lengthens the endurance time of rats on an accelerating rota-rod (Figure 2) and shortens the time that rats spend traversing a balance beam, which is mediated by H2 receptors [58, 61], indicating a promotion of histamine on cerebellum-mediated motor balance and motor coordination. Furthermore, microinjection of histamine into bilateral FNs narrowed stride width of footprint but did not influence wire suspension, whereas microinjection of histamine into bilateral INs increased stride length and promoted suspension [58] (Figure 3), suggesting that cerebellar histaminergic afferent system may precisely modulate trunk, proximal and distal muscles via biasing the FN and IN.Figure 2

Bottom Line: Histamine receptors, belonging to the family of G protein-coupled receptors, are widely present in the cerebellum.In this way, the histaminergic afferent system actively participates in the cerebellum-mediated motor balance and coordination and nonsomatic functions.On the other hand, considering the hypothalamus is a high regulatory center for autonomic and visceral activities, the hypothalamocerebellar histaminergic fibers/projections, bridging the nonsomatic center to somatic structure, may play a critical role in the somatic-nonsomatic integration.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Science and Technology and State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Mailbox 426, 22 Hankou Road, Nanjing, 210093 China.

ABSTRACT
Histaminergic afferent system of the cerebellum, having been considered as an essential component of the direct hypothalamocerebellar circuits, originates from the tuberomammillary nucleus in the hypothalamus. Unlike the mossy fibers and climbing fibers, the histaminergic afferent fibers, a third type of cerebellar afferents, extend fine varicose fibers throughout the cerebellar cortex and nuclei. Histamine receptors, belonging to the family of G protein-coupled receptors, are widely present in the cerebellum. Through these histamine receptors, histamine directly excites Purkinje cells and granule cells in the cerebellar cortex, as well as the cerebellar nuclear neurons. Therefore, the histaminergic afferents parallelly modulate these dominant components in the cerebellar circuitry and consequently influence the final output of the cerebellum. In this way, the histaminergic afferent system actively participates in the cerebellum-mediated motor balance and coordination and nonsomatic functions. Accordingly, histaminergic reagents may become potential drugs for clinical treatment of cerebellar ataxia and other cerebellar disease. On the other hand, considering the hypothalamus is a high regulatory center for autonomic and visceral activities, the hypothalamocerebellar histaminergic fibers/projections, bridging the nonsomatic center to somatic structure, may play a critical role in the somatic-nonsomatic integration.

No MeSH data available.


Related in: MedlinePlus