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The Long Journey of Pontine Nuclei Neurons: From Rhombic Lip to Cortico-Ponto-Cerebellar Circuitry.

ABSTRACT: The pontine nuclei (PN) are the largest of the precerebellar nuclei, neuronal assemblies in the hindbrain providing principal input to the cerebellum. The PN are predominantly innervated by the cerebral cortex and project as mossy fibers to the cerebellar hemispheres. Here, we comprehensively review the development of the PN from specification to migration, nucleogenesis and circuit formation. PN neurons originate at the posterior rhombic lip and migrate tangentially crossing several rhombomere derived territories to reach their final position in ventral part of the pons. The developing PN provide a classical example of tangential neuronal migration and a study system for understanding its molecular underpinnings. We anticipate that understanding the mechanisms of PN migration and assembly will also permit a deeper understanding of the molecular and cellular basis of cortico-cerebellar circuit formation and function.

SUBMITTER: Kratochwil CF

PROVIDER: S-EPMC5434118 | biostudies-other | 2017

REPOSITORIES: biostudies-other

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The Long Journey of Pontine Nuclei Neurons: From Rhombic Lip to Cortico-Ponto-Cerebellar Circuitry.

Kratochwil Claudius F CF Maheshwari Upasana U Rijli Filippo M FM

Frontiers in neural circuits 20170517

The pontine nuclei (PN) are the largest of the precerebellar nuclei, neuronal assemblies in the hindbrain providing principal input to the cerebellum. The PN are predominantly innervated by the cerebral cortex and project as mossy fibers to the cerebellar hemispheres. Here, we comprehensively review the development of the PN from specification to migration, nucleogenesis and circuit formation. PN neurons originate at the posterior rhombic lip and migrate tangentially crossing several rhombomere ...[more]

PMID: 28567005

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Project description:The subthalamic nucleus (STN) has been implicated in motor and non-motor tasks, and is an effective target of deep brain stimulation (DBS) for the treatment of Parkinson's disease, likely in part due to the STN's projections outside of the basal ganglia to other brain regions. While there is some evidence of a disynaptic connection between the STN and the cerebellum via the pontine nuclei (PN), how the STN modulates the activity of the neurons in the PN remains unknown. Here we addressed this question using a combination of anatomical tracings, optogenetics, and in vivo electrophysiology in both wild-type and transgenic mice of both sexes. Approximately half of recorded neurons in the PN, which were located primarily in the medial area, responded with short latency to both single pulses and trains of optogenetic stimulation of channelrhodopsin (ChR2)-expressing STN axons in awake, head-restrained mice. Furthermore, the increase in the activity of PN neurons correlated with the strength of activation of STN axons, suggesting that the STN projections to the PN could, in principle, encode information in a graded manner. In addition, transsynaptic retrograde tracing confirmed that the STN sends disynaptic projections to the cerebellar cortex. These results suggest that the STN sends robust functional projections to the PN, which then propagate to the cerebellum, and have important implications for understanding motor control of normal conditions, and Parkinsonian symptoms, where this pathway may have a role in the therapeutic efficacy of STN DBS.Significance StatementThe primary excitatory nucleus in the basal ganglia, the subthalamic nucleus, is known to play a role in pathways modulating movement. The pontine nuclei are the main precerebellar nuclei, which transmit signals through their axonal projections to the cerebellum as mossy fibers. The pathway we have functionally characterized in this paper represents an additional cortex-independent pathway capable of relaying information between the basal ganglia and cerebellum. The effectiveness of subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease suggests that this pathway could be explored as an avenue of investigation for therapeutic purposes.

Dataset Information

The Long Journey of Pontine Nuclei Neurons: From Rhombic Lip to Cortico-Ponto-Cerebellar Circuitry.

Publications

The Long Journey of Pontine Nuclei Neurons: From Rhombic Lip to Cortico-Ponto-Cerebellar Circuitry.

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