Hypomyelination leads to alterations in inhibitory function and parvalbumin-positive neuron density in the auditory cortex

ABSTRACT

Myelination of central nervous system axons increases the conduction speed of neural impulses and contributes to the function and maintenance of neural circuits. Accordingly, loss of myelin leads to axonal loss and to severe brain dysfunction. In contrast, much less is known about the functional consequences of mild hypomyelination on central network connectivity. To address this gap in knowledge, we studied mice that have mild hypomyelination due to loss of oligodendrocyte ErbB receptor signaling. We focused on the primary auditory cortex (A1) due to the crucial role that temporal precision plays in the processing of auditory information. We find that loss of oligodendrocyte ErbB receptor signaling causes reduction in myelin in A1. We mapped and quantified the intracortical inputs to L2/3 neurons using laser-scanning photostimulation combined with patch clamp recordings. We found that hypomyelination reduces inhibitory connections to L2/3 neurons without affecting excitatory inputs, thus altering excitatory/inhibitory balance. Remarkably, these effects are not associated with changes in the expression of GABAergic and glutamatergic synaptic components, but with a reduction of parvalbumin (PV) neuron density and PV mRNA levels. These results demonstrate that mild hypomyelination can impact cortical neuronal networks and cause a network shift towards excitation.