2025/05/09 by Benjamin S. Summers, Catherine A. Blizzard, Raphael Ricci +6 · 1 voice
Biochemistry, Genetics and Molecular Biology · Neuroscience · #Mitochondrial Function and Pathology #Neurogenesis and neuroplasticity mechanisms #Neuroscience and Neuropharmacology Research
paper · pdf · doi:10.1523/eneuro.0113-25.2025
openalex publication_date 2025/05/09 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22
Oligodendrocyte progenitor cells (OPCs) receive synaptic input from a diverse range of neurons in the developing and adult brain. Understanding whether the neuronal populations that synapse with OPCs in the healthy brain is altered by demyelination and/or remyelination may support the advancement of neuroprotective or myelin repair strategies being developed for demyelinating diseases such as multiple sclerosis. To explore this possibility, we employed cre-lox transgenic technology to facilitate the infection of OPCs by a modified rabies virus, enabling the retrograde monosynaptic tracing of neuron→OPC connectivity. In the healthy adult mouse, OPCs in the corpus callosum primarily received synaptic input from ipsilateral cortical neurons. Of the cortical neurons, ∼50% were layer V pyramidal cells. Cuprizone demyelination reduced the total number of labeled neurons. However, the frequency/kinetics of mini-excitatory postsynaptic currents recorded from OPCs appeared preserved. Of particular interest, demyelination increased the number of labeled layer II/III pyramidal neurons and also increased at the expense of layer V pyramidal neurons, a change that was largely ameliorated by remyelination. These data suggest that in the healthy adult mouse brain, callosal OPCs primarily receive synaptic input from cortical layer V pyramidal neurons. However, callosal demyelination is associated with a population switch and OPCs equally synapse with layer II/III and V pyramidal neurons to synapse with OPCs, until myelin is restored.