Perineuronal net degradation causes a delayed change in resting and sound evoked responses in the mouse auditory...

Perineuronal nets (PNNs) are extracellular matrix assemblies that preferentially cover parvalbumin-expressing (PV+) interneurons in the neocortex. PV+ cells and PNNs are impaired in a variety of neurodevelopmental disorders including Fragile X Syndrome and schizophrenia. In both of these disorders, electroencephalograph (EEG) recordings show similar phenotypes, including elevated resting gamma band power and reduced temporal fidelity in the 40 Hz auditory steady state response (ASSR). Whether there is a causal link between PNN integrity and EEG abnormalities remains unclear. We tested this link by recording EEG responses in the auditory cortex (AC) in wildtype mice in which PNNs were enzymatically degraded (Chondroitinase ABC or ChABC). EEGs were recorded at two different time points (4- or 14-days post injection, cross-sectional design). In comparison to saline control, ChABC injected mice showed a ∼50 % reduction in PNN density after 4-days. However, there was no difference in resting EEG power spectral density, auditory event-related potential amplitudes or ASSR temporal fidelity between saline and ChABC mice. At the 14-day time point, there was a recovery of PNN density in the AC. Interestingly, EEG responses were abnormal at this time point, with elevated gamma band activity and reduced ASSR temporal fidelity. Thus, the electrophysiological consequences of PNN loss are not seen acutely, but over a delayed time course, suggesting abnormal plasticity after a circuit perturbation. Taken together, these data indicate acute shaping of auditory cortical responses is less dependent on PNNs, but long-term stability of responses following a circuit perturbation depends on the integrity of PNNs.