Chemogenetic activation of oligodendrocytes modulates behavioural processes

Experience and neuronal activity can induce dynamic changes in myelination during development and in adult life, suggesting a new form of plasticity to adapt brain function to environmental stimuli. Myelin remodeling is driven mainly by newly-formed oligodendrocytes from precursors cells. However, the role of mature oligodendrocytes in plastic changes of myelin is less known. In order to analyze the role of mature oligodendrocytes, we have used inducible transgenic mice expressing the DREADD receptor hM3Dq in PLP+ myelinating cells. In vivo chronic CNO treatment shortened the nodes of Ranvier length while lengthened the paranodes. We therefore tested the impact of this treatment on behavioral processes. CNO treatment translated in changes in innate-emotional behavior and in the extinction of aversive memories. Thus, chronic oligodendrocytes stimulation impaired short-term extinction in auditory fear-conditioning tests, with unaffected memory acquisition. Hippocampus, basolateral amygdala and the prefrontal cortex circuits are known to be involved in the control of extinction of aversive memories. CNO treatment modulated neuronal c-Fos expression after fear conditioning in all regions, a mechanism that could contribute to the impairment in fear memory extinction. Altogether, out results demonstrated that mature oligodendrocytes stimulation induces plastic changes in myelination which have a profound influence over mice behavior.