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Corticotropin-releasing factor receptor types 1 and 2 are differentially expressed in pre- and post-synaptic elements in the post-natal developing rat cerebellum
Ist Teil von
The European journal of neuroscience, 2003-08, Vol.18 (3), p.549-562
Ort / Verlag
Oxford, UK: Blackwell Science, Ltd
Erscheinungsjahr
2003
Quelle
Wiley-Blackwell Journals
Beschreibungen/Notizen
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.