Altered cerebellar response to somatosensory stimuli in the Cntnap2 mouse model of autism

Marta Fernández, Carlos A. Sánchez-León, Javier Llorente, Teresa Sierra-Arregui, Shira Knafo, Javier Márquez-Ruiz, Olga Peñagarikano

Research output: Contribution to journalArticlepeer-review

Abstract

Atypical sensory processing is currently included within the diagnostic criteria of autism. The cerebellum is known to integrate sensory inputs of different modalities through its connectivity to the cerebral cortex. Interestingly, cerebellar malformations are among the most replicated features found in postmortem brain of individuals with autism. We studied sensory processing in the cerebellum in a mouse model of autism, knockout (KO) for the Cntnap2 gene. Cntnap2 is widely expressed in Purkinje cells (PCs) and has been recently reported to regulate their morphology. Further, individuals with CNTNAP2 mutations display cerebellar malformations and CNTNAP2 antibodies are associated with a mild form of cerebellar ataxia. Previous studies in the Cntnap2 mouse model show an altered cerebellar sensory learning. However, a physiological analysis of cerebellar function has not been performed yet. We studied sensory evoked potentials in cerebellar Crus I/II region on electrical stimulation of the whisker pad in alert mice and found striking differences between wild-type and Cntnap2 KO mice. In addition, single-cell recordings identified alterations in both sensory-evoked and spontaneous firing patterns of PCs. These changes were accompanied by altered intrinsic properties and morphologic features of these neurons. Together, these results indicate that the Cntnap2 mouse model could provide novel insight into the pathophysiological mechanisms of autism core sensory deficits.

Original languageEnglish
Article numberENEURO.0333-21.2021
JournaleNeuro
Volume8
Issue number5
DOIs
StatePublished - 1 Sep 2021

Keywords

  • Autism
  • Cerebellum
  • Cntnap2
  • Complex spike
  • Purkinje
  • Sensory stimuli

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