Abstract
ABSTRACTMyelination increases axonal conduction velocity and contributes to neural circuit function. Consequently, disruption of brain myelin causes behavioral and cognitive defects. Myelin was thought to be restricted to excitatory neurons, and studies on dysmyelination focused primarily on these cells. However, axons of inhibitory neurons are also myelinated [1], but the effects of myelin on inhibitory circuits are unknown. We thus studied the impact of mild hypomyelination on excitatory and inhibitory connectivity in the primary auditory cortex (A1) using well characterized mouse models with loss of oligodendrocyte ErbB receptor signaling [2, 3]. We found that mice with mild hypomyelination have reduced functional inhibitory connections to A1 L2/3 neurons without changes in excitatory inputs, resulting in altered excitatory/inhibitory balance. These effects are not associated with altered expression of GABAergic and glutamatergic synaptic components, but with reduced density of parvalbumin-positive (PV+) neurons and axons, and reduced PV mRNA levels. We found a remarkable correlation between MBP and PV expression, while immunostaining shows that hypomyelination occurs in both PV+ and PV− axons. Together, the results demonstrate that mild hypomyelination can impact cortical neuronal networks, reducing inhibitory activity, and shifting networks towards excitation.Impact StatementMild hypomyelination alters excitatory/inhibitory balance in the primary auditory cortex by reducing the number of parvalbumin-positive interneurons and reducing inhibition.
Publisher
Cold Spring Harbor Laboratory