Elsevier

Brain Research Reviews

Volume 52, Issue 1, 30 August 2006, Pages 93-106
Brain Research Reviews

Review
The cerebellar-hypothalamic circuits: Potential pathways underlying cerebellar involvement in somatic-visceral integration

https://doi.org/10.1016/j.brainresrev.2006.01.003Get rights and content

Abstract

The cerebellum has been considered only as a classical subcortical center for motor control. However, accumulating experimental and clinical evidences have revealed that the cerebellum also plays an important role in cognition, for instance, in learning and memory, as well as in emotional behavior and in nonsomatic activities, such as visceral and immunological responses. Although it is not yet clear through which pathways such cerebellar nonsomatic functions are mediated, the direct bidirectional connections between the cerebellum and the hypothalamus, a high autonomic center, have recently been demonstrated in a series of neuroanatomical investigations on a variety of mammals and indicated to be potential pathways underlying the cerebellar autonomic modulation. The direct hypothalamocerebellar projections originate from the widespread hypothalamic nuclei/areas and terminate in both the cerebellar cortex as multilayered fibers and the cerebellar nuclei. Immunohistochemistry studies have offered fairly convincing evidence that some of these projecting fibers are histaminergic. It has been suggested that through their excitatory effects on cerebellar cortical and nuclear cells mediated by metabotropic histamine H2 and/or H1 receptors, the hypothalamocerebellar histaminergic fibers participate in cerebellar modulation of somatic motor as well as non-motor responses. On the other hand, the direct cerebellohypothalamic projections arise from all cerebellar nuclei (fastigial, anterior and posterior interpositus, and dentate nuclei) and reach almost all hypothalamic nuclei/areas. Neurophysiological and neuroimaging studies have demonstrated that these connections may be involved in feeding, cardiovascular, osmotic, respiratory, micturition, immune, emotion, and other nonsomatic regulation. These observations provide support for the hypothesis that the cerebellum is an essential modulator and coordinator for integrating motor, visceral and behavioral responses, and that such somatic-visceral integration through the cerebellar circuitry may be fulfilled by means of the cerebellar-hypothalamic circuits.

Introduction

Our knowledge of cerebellar physiological function has long been confined to its motor control. However, the past decade has witnessed significant advances in experimental neuroanatomical, neurophysiological, behavioral and functional brain imaging studies on cerebellar nonsomatic functions, as well as in clinical observations on patients with cerebellar lesions. These intriguing findings, such as the fastigial pressor response (FPR) (Reis and Golanov, 1997), the alterations in feeding behavior and nutritional organization after lesioning rat cerebellar cortex (Scalera, 1991, Mahler, 1993), and the cerebellar cognitive affective syndrome (Schmahmann and Sherman, 1998), greatly expand the traditional understanding of cerebellar roles in central nervous system. In fact, the cerebellum is not only a subcortical center for motor control participating in the sensomotor integration, but also an essential node in the central integration of somatic and visceral activities, which contributes to generate integrated and coordinated somatic-visceral responses to adapt to the changes of internal and external environments.

Therefore, naturally, a question is raised which neural pathways provide the substantial foundation for such cerebellar nonsomatic functions. It has long been well known that there are afferent and efferent connections between the cerebellum and the motor cortex as well as the motor nuclei in brainstem (Schmahmann and Pandya, 1997, Teune et al., 2000). In addition, the projections of the cerebellum to the brainstem regions relevant to visceral regulation have also been documented (Homma et al., 1995, Teune et al., 2000). Although several studies support that the FPR seems to be relative to the multi-synaptic projections of cerebellum to brainstem (Bradley et al., 1987, Homma et al., 1995, Reis and Golanov, 1997), the autonomic responses evoked by stimulating cerebellum were abolished following a precollicular decerebration (Zanchetti and Zoccolini, 1954, Supple et al., 1988). Thus, it is imperfect that the explanation for the cerebellar modulation on various visceral activities is simply mediated the cerebello–brainstem pathways. In reality, the cerebellar influences on autonomic responses/activities are most likely to be related to higher autonomic center(s) above the mesencephalon. Recent numerous neuroanatomical studies using retrograde and anterograde tracing techniques revealed the direct bidirectional connections between the cerebellum and the hypothalamus (Dietrichs, 1984, Dietrichs and Haines, 1984, Dietrichs et al., 1992, Dietrichs et al., 1994, Haines and Dietrichs, 1984, Haines et al., 1985, Haines et al., 1990, Çavdar et al., 2001a, Çavdar et al., 2001b), i.e., the hypothalamocerebellar projections and the cerebellohypothalamic projections, which constitute the cerebellar-hypothalamic circuits. Considering that the hypothalamus is an important high autonomic center for regulation of visceral functions, it is suggested that the cerebellar-hypothalamic circuits may be potential neuroanatomical substrates underlying the cerebellar extensive modulation of nonsomatic activities.

Section snippets

Hypothalamocerebellar projections

The direct hypothalamocerebellar projections were first definitively presented by Dietrichs (1984) in his pioneering study on the cat that placed wheat germ agglutinin-horseradish peroxidase as retrograde tracers into the cerebellar cortex. A subsequent series of neuroanatomical investigations on various mammals including rats (Dietrichs et al., 1992), tree shrews (Haines et al., 1985), greater bushbabies (Dietrichs and Haines, 1984), squirrel monkeys (Haines and Dietrichs, 1984, Haines et al.,

Cerebellohypothalamic projections

Following the studies used anterograde and retrograde tracing techniques (Dietrichs and Haines, 1984, Haines and Dietrichs, 1984, Haines et al., 1985, Haines et al., 1990, Çavdar et al., 2001a, Çavdar et al., 2001b), the direct projections from the cerebellar nuclei to the hypothalamus have been revealed (Fig. 1). The cerebellohypothalamic projections arise from all cerebellar nuclei (fastigial, anterior and posterior interpositus, and dentate nuclei), pass through the superior cerebellar

Cerebellum and its nonsomatic modulation

Following the findings of (i) the direct neural circuits between the cerebellum and the hypothalamus, (ii) the indirect cerebellar-hypothalamic connections mediated by the basilar pontine nuclei, nucleus reticularis tegmenti pontis, and lateral reticular nucleus (Brodal and Walberg, 1977, Azizi et al., 1981, Dietrichs et al., 1985, Aas and Brodal, 1989, Mihailoff, 1993, Liu and Mihailoff, 1999), and (iii) other direct/indirect (e.g., through hypothalamus) connections between the cerebellum and

Conclusion

The hypothesis that the cerebellum participates in a multitude of brain functions considerably beyond those related to the somatomotor system has been supported by a growing body of experimental and clinical evidences. In fact, an intact motor response involves somatic, visceral, behavioral and cognitive components. The cerebellar modulation on nonsomatic functions, especially above-mentioned visceral activities such as ingestion, circulation, and respiration, is actually an element of the

Acknowledgments

Researches from our laboratory were supported by grants 39770249, 30070250, 30370462 and the NSFC/RGC Joint Research Scheme 30318004 from the National Natural Science Foundation of China, RFDP grant 20010284021, 20050284025 from the State Educational Ministry of China and grants BK97045, BK2002083 from the Natural Science Foundation of Jiangsu Province of China. Partial works were also supported by a grant-in-aid of “985 Project” from Nanjing University.

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