H2-K super(b) and H2-D super(b) regulate cerebellar long-term depression and limit motor learning

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 106; no. 16; pp. 6784 - 6789
• Main Authors: McConnell, Michael J, Huang, Yanhua H, Datwani, Akash, Shatz, Carla J
• Format: Journal Article
• Language: English
• Published: 21.04.2009
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0902018106

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 super(b) and H2-D super(b), are co-expressed by Purkinje cells (PCs). In the cerebellum of mice deficient for both H2-K super(b) and H2-D super(b) (K super(b)D super(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 super(b)D super(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 super(b)D super(b-/-) mice than in WT cohorts. These physiological and behavioral phenotypes in K super(b)D super(b-/-) mice reveal a surprising role for classical MHCI molecules in synaptic plasticity and motor learning.