Aberrant dendritic branching and sensory inputs in the superficial dorsal horn of mice lacking CaMKIIalpha autophosphorylation.
Superficial dorsal horn neurones undergo marked structural and functional activity-dependent development during the early postnatal period, but little is known about the molecular mechanisms underlying these changes. Calcium signalling, through activation and autophosphorylation of CaMKII, has been shown to play a major role in the maturation of neuronal morphology and connectivity in the cortex. Here, we show that the normal structural and functional development of superficial dorsal horn neurones requires CaMKII autophosphorylation at the Thr286 residue. The dendritic branching of neurones from mice containing a point mutation at this site (T286A) was significantly increased compared with wild-type littermates. This was accompanied by significant increases in receptive field size, recorded from intact preparations. Whole-cell patch clamp recordings of superficial dorsal horn slices revealed a selective deficit in low-threshold A fibre-evoked synaptic input. These results show that CaMKII autophosphorylation is required for the normal development of spinal sensory circuits.
Pattinson
Damian
D
Department of Anatomy and Developmental Biology, University College London, London, UK. damian.pattinson@kcl.ac.uk
Baccei
Mark
M
Karadottir
Ragnhildur
R
Torsney
Carole
C
Moss
Andrew
A
McCutcheon
Jaime
J
Giese
K Peter
KP
Fitzgerald
Maria
M
D000344:Afferent Pathways / Q000033:anatomy & histology*; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D003712:Dendrites / Q000473:pathology / Q000648:ultrastructure*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009475:Neurons, Afferent / Q000166:cytology / Q000502:physiology; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D017354:Point Mutation; D020671:Posterior Horn Cells / Q000166:cytology / Q000254:growth & development / Q000473:pathology
D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases