alphaCaMKII Is essential for cerebellar LTD and motor learning.
Activation of postsynaptic alpha-calcium/calmodulin-dependent protein kinase II (alphaCaMKII) by calcium influx is a prerequisite for the induction of long-term potentiation (LTP) at most excitatory synapses in the hippocampus and cortex. Here we show that postsynaptic LTP is unaffected at parallel fiber-Purkinje cell synapses in the cerebellum of alphaCaMKII(-/-) mice. In contrast, a long-term depression (LTD) protocol resulted in only transient depression in juvenile alphaCaMKII(-/-) mutants and in robust potentiation in adult mutants. This suggests that the function of alphaCaMKII in parallel fiber-Purkinje cell plasticity is opposite to its function at excitatory hippocampal and cortical synapses. Furthermore, alphaCaMKII(-/-) mice showed impaired gain-increase adaptation of both the vestibular ocular reflex and optokinetic reflex. Since Purkinje cells are the only cells in the cerebellum that express alphaCaMKII, our data suggest that an impairment of parallel fiber LTD, while leaving LTP intact, is sufficient to disrupt this form of cerebellar learning.
Hansel
Christian
C
Department of Neuroscience, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
de Jeu
Marcel
M
Belmeguenai
Amor
A
Houtman
Simone H
SH
Buitendijk
Gabriëlle H S
GH
Andreev
Dmitri
D
De Zeeuw
Chris I
CI
Elgersma
Ype
Y
D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002531:Cerebellum / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D005260:Female; D005838:Genotype; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007858:Learning / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009473:Neuronal Plasticity / Q000502:physiology; D018408:Patch-Clamp Techniques; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011689:Purkinje Cells / Q000166:cytology / Q000201:enzymology / Q000502:physiology; D012027:Reflex, Vestibulo-Ocular / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology; D009435:Synaptic Transmission / Q000502:physiology; D013997:Time Factors; D000096926:Benzenesulfonamides
D001596:Benzylamines; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; C072105:KN 93; D000096926:Benzenesulfonamides