Knafo, S. | bioRxiv Science

bioRxiv2021

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

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 cerebellar integration of sensory information in a mouse model of autism, knockout for the Cntnap2 gene. Cntnap2 is widely expressed in Purkinje cells 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 upon electrical stimulation of the whisker pad in alert mice and found striking differences between WT and Cntnap2 KO mice. In addition, single-cell recordings identified alterations in both sensory-evoked and spontaneous firing patterns of Purkinje cells. These changes were accompanied by altered intrinsic properties and morphological features of these neurons. Together, these results indicate that the Cntnap2 mouse model could provide novel insight into the pathophysiological mechanisms of ASD core sensory deficits.

neuroscience↗

bioRxiv2020

Unicellular associative conditioning: an interspecies analysis

The capacity to learn new systemic behaviour is a fundamental issue to understand the adaptive mechanisms involved in cellular evolution. We have recently observed, in a preliminary analysis, the emergence of conditioned behaviour in individual amoebae cells. In these experiments, cells were able to acquire new migratory conduct and remember it for long periods of their cellular cycle, forgetting it later on. Here, following a similar conceptual framework of Pavlovs experiments, we have exhaustively studied the migration trajectories of more than 2000 individual cells belonging to three different species: Amoeba proteus, Metamoeba leningradensis, and Amoeba borokensis. Fundamentally, we have analysed several properties of conditioned cells, such as the intensity of the responses, the directionality persistence, the total distance traveled, the directionality ratio, the average speed, and the persistence times. We have observed that these three species can modify the systemic response to a specific stimulus by associative conditioning. Our main analysis shows that such new behaviour is very robust and presents a similar structure of migration patterns in the three species, which was characterized by the presence of conditioning for long periods, remarkable straightness in their trajectories and strong directional persistence. Our quantitative results, compared with other studies on complex cellular responses in bacteria, protozoa, fungus-like organisms and metazoans, allow us to conclude that cellular associative conditioning might be a widespread characteristic of unicellular organisms. This finding could be essential to understand some key evolutionary principles involved in increasing the cellular adaptive fitness to microenvironments.

systems biology↗