Corticotropin-releasing factor receptor types 1 and 2 are differentially expressed in pre- and post-synaptic elements in the post-natal developing rat cerebellum.
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 immunoreactivity 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.
Swinny
J D
JD
Laboratory for Cell Biology and Electron Microscopy, Department of Cell Biology, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands. j.d.swinny@med.rug.nl
Kalicharan
D
D
Blaauw
E H
EH
Ijkema-Paassen
J
J
Shi
F
F
Gramsbergen
A
A
van der Want
J J L
JJ
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development* / Q000378:metabolism*; D015153:Blotting, Western; D002531:Cerebellum / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure
D020033:Protein Isoforms; D018019:Receptors, Corticotropin-Releasing Hormone