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.

Methods
Chronic ECoG and LFP recordings were performed using in-house made electrodes of platinum iridium wire (101R-5T, 90% Pt, 10% Ir, complete diameter of 200 µm with 127 µm metal  diameter, Science Products). The perfluoroalkoxy alkanes (PFA) coated wire platinum-iridium wire was only exposed at the tip to record the local field potential (LFP). For placement of the recording electrode, animals were anesthetized with isoflurane (3%, flow rate 0.8 L/min with maintenance 1.5–1.8%, flow rate 0.6 L/min). A 1 cm midline sagittal incision was made starting above the interaural line and extending along the neck to create a pocket for subcutaneous placement of the transmitter along the dorsal flank of the animal. The recording electrodes in each hemi-sphere (stereotaxic coordinates relative to bregma: S1; –0.15 mm anterior and ± 0.30 mm lateral; for LFP; ventral 0.75 mm, V1; 0.40 mm anterior and ± 0.30 mm lateral; for LFP; ventral 0.75 mm) and ground electrode (6 mm posterior and 1 mm lateral) were implanted sub durally through small holes drilled in the skull, held in place with stainless steel screws (A2-70, Jeveka) and subsequently sealed with dental cement. Mice were provided with Metachem analgesic (0.1 mg per kg) after surgery and allowed to recover for 4–7 days before recordings. To obtain multiple hours recordings of ECoG-LFP at multiple weeks, mice remained in their home cage during an overnight recording session. ECoG–LFP data were collected using a ME2100-system (Multi channel Systems); ECoG-LFP data were acquired at a sampling rate of 2 kHz using the multi-channel experimenter software (Multi channel systems). The data was exported and saved as EDF format using Multichannel Datamanager 1.102.18296 (Multi channel systems)