Corticotropin-releasing factor receptor types 1 and 2 are differentially expressed in pre- and post-synaptic elements in the post-natal developing rat cerebellum

Authors

  • J. D. Swinny,

    1. Laboratory for Cell Biology and Electron Microscopy, Department of Cell Biology, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, the Netherlands
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  • D. Kalicharan,

    1. Laboratory for Cell Biology and Electron Microscopy, Department of Cell Biology, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, the Netherlands
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  • E. H. Blaauw,

    1. Laboratory for Cell Biology and Electron Microscopy, Department of Cell Biology, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, the Netherlands
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  • J. Ijkema-Paassen,

    1. Department of Medical Physiology, Graduate School of Behavioural and Cognitive Neuroscience University of Groningen, the Netherlands
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  • F. Shi,

    1. Department of Membrane Cell Biology, University of Groningen, the Netherlands
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  • A. Gramsbergen,

    1. Department of Medical Physiology, Graduate School of Behavioural and Cognitive Neuroscience University of Groningen, the Netherlands
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  • J. J. L. Van Der Want

    1. Laboratory for Cell Biology and Electron Microscopy, Department of Cell Biology, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, the Netherlands
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: Dr J. D. Swinny, as above.
E-mail: j.d.swinny@med.rug.nl

Abstract

Corticotropin-releasing factor (CRF)-like proteins act via two G-protein-coupled receptors (CRF-R1 and CRF-R2) playing important neuromodulatory roles in stress responses and synaptic plasticity. The cerebellar expression of corticotropin-releasing factor-like ligands has been well documented, but their receptor localization has not. This is the first combination of a light microscopic and ultrastructural study to localize corticotropin-releasing factor receptors immunohistologically in the developing rat cerebellum. Both CRF-R1 and CRF-R2 were expressed in climbing fibres from early stages (post-natal day 3) to the adult, but CRF-R2 immmunoreactivity was only prominent throughout the molecular layer in the posterior cerebellar lobules. CRF-R1 immunoreactivity was concentrated in apical regions of Purkinje cell somata and later in primary dendrites exhibiting a diffuse cytoplasmic appearance. In Purkinje cells, CRF-R1 immunoreactivity was never membrane bound post-synaptically in dendritic spines while CRF-R2 immunoreactivity was found on plasmic membranes of Purkinje cells from post-natal day 15 onwards. We conclude that the localization of these receptors in cerebellar afferents implies their pre-synaptic control of the release of corticotropin-releasing factor-like ligands, impacting on the sensory information being transmitted from afferents. Furthermore, the fact that CRF-R2 is membrane bound at synapses, while CRF-R1 is not, suggests that ligands couple to CRF-R2 via synaptic transmission and to CRF-R1 via volume transmission. Finally, the distinct expression profiles of receptors along structural domains of Purkinje cells suggest that the role for these receptors is to modulate afferent inputs.

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