Multichannel ECoG and LFP from control and cuprizone mice

Parvalbumin-positive (PV+) γ-aminobutyric acid (GABA)
interneurons are critically involved in producing rapid network
oscillations and cortical microcircuit computations but the significance
of PV+ axon myelination to the temporal features of inhibition
remains elusive. Here using toxic and genetic models of demyelination and
dysmyelination, respectively, we find that loss of compact myelin reduces
PV+ interneuron presynaptic terminals, increases failures and the
weak phasic inhibition of pyramidal neurons abolishes optogenetically
driven gamma oscillations in vivo. Strikingly, during periods of
quiet wakefulness selectively theta rhythms are amplified and accompanied
by highly synchronized interictal epileptic discharges. In support of a
causal role of impaired PV-mediated inhibition, optogenetic activation of
myelin-deficient PV+ interneurons attenuated the power of slow
theta rhythms and limited interictal spike occurrence. Thus, myelination
of PV+ axons is required to consolidate fast inhibition of
pyramidal neurons and enable behavioral state-dependent modulation of
local circuit synchronization.