Decreased reproducibility and abnormal experience-dependent plasticity of network dynamics in Fragile X circuits

Abstract

Fragile X syndrome is a neurodevelopmental disorder associated with a broad range of neural phenotypes. Interpreting these findings has proven challenging because some phenotypes may reflect compensatory mechanisms or normal forms of plasticity differentially engaged by experiential differences. To help minimize compensatory and experiential influences, we used an ex vivo approach to study network dynamics and plasticity of cortical microcircuits. In Fmr1−/y circuits, the spatiotemporal structure of Up-states was less reproducible, suggesting alterations in the plasticity mechanisms governing network activity. Chronic optical stimulation revealed normal homeostatic plasticity of Up-states, however, Fmr1−/y circuits exhibited abnormal experience-dependent plasticity as they did not adapt to chronically presented temporal patterns in an interval-specific manner. These results, suggest that while homeostatic plasticity is normal, Fmr1−/y circuits exhibit deficits in the ability to orchestrate multiple forms of synaptic plasticity and to adapt to sensory patterns in an experience-dependent manner—which is likely to contribute to learning deficits.