Format

Send to

Choose Destination
Dis Model Mech. 2018 Jul 10;11(7). pii: dmm033258. doi: 10.1242/dmm.033258.

Cerebellar synapse properties and cerebellum-dependent motor and non-motor performance in Dp71-null mice.

Author information

1
Molecules and Circuits Department, Paris-Saclay Institute of Neuroscience (Neuro-PSI), UMR 9197, Université Paris Sud, CNRS, Université Paris Saclay, 91405 Orsay, France.
2
Cognition and Behavior Department, Paris-Saclay Institute of Neuroscience (Neuro-PSI), UMR 9197, Université Paris Sud, CNRS, Université Paris Saclay, 91405 Orsay, France.
3
Molecules and Circuits Department, Paris-Saclay Institute of Neuroscience (Neuro-PSI), UMR 9197, Université Paris Sud, CNRS, Université Paris Saclay, 91405 Orsay, France micaela.galante@u-psud.fr cyrille.vaillend@u-psud.fr.
4
Cognition and Behavior Department, Paris-Saclay Institute of Neuroscience (Neuro-PSI), UMR 9197, Université Paris Sud, CNRS, Université Paris Saclay, 91405 Orsay, France micaela.galante@u-psud.fr cyrille.vaillend@u-psud.fr.

Abstract

Recent emphasis has been placed on the role that cerebellar dysfunctions could have in the genesis of cognitive deficits in Duchenne muscular dystrophy (DMD). However, relevant genotype-phenotype analyses are missing to define whether cerebellar defects underlie the severe cases of intellectual deficiency that have been associated with genetic loss of the smallest product of the dmd gene, the Dp71 dystrophin. To determine for the first time whether Dp71 loss could affect cerebellar physiology and functions, we have used patch-clamp electrophysiological recordings in acute cerebellar slices and a cerebellum-dependent behavioral test battery addressing cerebellum-dependent motor and non-motor functions in Dp71-null transgenic mice. We found that Dp71 deficiency selectively enhances excitatory transmission at glutamatergic synapses formed by climbing fibers (CFs) on Purkinje neurons, but not at those formed by parallel fibers. Altered basal neurotransmission at CFs was associated with impairments in synaptic plasticity and clustering of the scaffolding postsynaptic density protein PSD-95. At the behavioral level, Dp71-null mice showed some improvements in motor coordination and were unimpaired for muscle force, static and dynamic equilibrium, motivation in high-motor demand and synchronization learning. Dp71-null mice displayed altered strategies in goal-oriented navigation tasks, however, suggesting a deficit in the cerebellum-dependent processing of the procedural components of spatial learning, which could contribute to the visuospatial deficits identified in this model. In all, the observed deficits suggest that Dp71 loss alters cerebellar synapse function and cerebellum-dependent navigation strategies without being detrimental for motor functions.

KEYWORDS:

Cerebellum; Cognitive deficit; Dp71; Dystrophin; Glutamatergic transmission; Motor coordination; Purkinje neuron

Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center