Perineuronal nets (PNNs) are specialized complexes of extracellular matrix molecules that surround the somata of fast-spiking neurons throughout the vertebrate brain. PNNs are particularly prevalent throughout the auditory brainstem, which transmits signals with high speed and precision. It is unknown whether PNNs contribute to the fast-spiking ability of the neurons they surround. Whole-cell recordings were made from medial nucleus of the trapezoid body (MNTB) principal neurons in acute brain slices from P21-27 mice. PNNs were degraded by incubating slices in chondroitinase (ChABC) and were compared to slices that were treated with a control enzyme (Penicillinase). ChABC treatment did not affect the ability of MNTB neurons to fire at up to 1000 Hz when driven by current pulses. However, f-I (frequency/intensity) curves constructed by injecting Gaussian white noise currents superimposed on DC current steps showed that ChABC treatment reduced the gain of spike output. An increase in spike threshold may have contributed to this effect, which is consistent with the observation that spikes in ChABC-treated cells were delayed relative to control-treated cells. In addition, parvalbumin-expressing fast-spiking cortical neurons in >P70 slices that were treated with ChABC also had reduced excitability and gain. The development of PNNs around somata of fast-spiking neurons may be essential for fast and precise sensory transmission and synaptic inhibition in the brain.
Significance Statement Perineuronal nets (PNNs) are extracellular matrix specializations that surround the somata of fast-spiking inhibitory neurons in most areas of the brain. Although PNN development correlates with the restriction of plasticity and their disruption causes enhancement of plasticity in vivo, it is unclear how PNNs affect the neurons they surround. In the present study, mature neurons were stimulated with fluctuating currents to measure their input/output functions after degradation of PNNs with the enzyme chondroitinase. Both MNTB principal neurons and PV+ fast-spiking cortical interneurons treated with chondroitinase exhibited reduced excitability compared to control-treated cells. Increased spike threshold may underlie this change in gain. Thus, PNNs increase the evoked activity of fast-spiking neurons and could control plasticity by enhancing synaptic inhibition.