H2-K(b) and H2-D(b) regulate cerebellar long-term depression and limit motor learning.
There are more than 50 class I MHC (MHCI) molecules in the mouse genome, some of which are now known to be expressed in neurons; however, the role of classical MHCI molecules in synaptic plasticity is unknown. We report that the classical MHCI molecules, H2-K(b) and H2-D(b), are co-expressed by Purkinje cells (PCs). In the cerebellum of mice deficient for both H2-K(b) and H2-D(b) (K(b)D(b-/-)), there is a lower threshold for induction of long-term depression (LTD) at parallel fiber to PC synapses. This change may be a result of additional glutamate release observed at K(b)D(b-/-) CF to PC synapses, which are thought to "train" the cerebellar circuit. A behavioral correlate of cerebellar LTD is motor learning; acquisition and retention of a Rotarod behavioral task is significantly better in K(b)D(b-/-) mice than in WT cohorts. These physiological and behavioral phenotypes in K(b)D(b-/-) mice reveal a surprising role for classical MHCI molecules in synaptic plasticity and motor learning.
McConnell
Michael J
MJ
Bio-X and Department of Biology, Stanford University, Stanford, CA 94305, USA.
Huang
Yanhua H
YH
Datwani
Akash
A
Shatz
Carla J
CJ
D000818:Animals; D001369:Axons / Q000378:metabolism; D002531:Cerebellum / Q000196:embryology / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials; D005971:Glutamates / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D066298:In Vitro Techniques; D007858:Learning / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000502:physiology*; D011689:Purkinje Cells / Q000378:metabolism; D012153:Retention, Psychology; D045442:Rotarod Performance Test; D013569:Synapses / Q000378:metabolism
D005971:Glutamates; D015395:Histocompatibility Antigens Class I