BREVICAN-DEFICIENT MICE SHOW IMPROVED TEMPORAL PROCESSING IN THE INFERIOR COLLICULUS

The proteoglycan brevican is a major component of the extracellular matrix of perineuronal nets and is highly enriched in the perisynaptic space where it appears to contribute to synaptic plasticity, stability, and health. Brevican is part of perineuronal nets at various stations of the auditory pathway. We have studied the role of brevican for spectral and temporal coding in the IC by using brevican knockout (bcan-/-) mice. To this aim, we performed in vivo electrophysiological recordings from neurons of the IC from systemic bcan-/- and bcan+/+ littermates. Responses of IC neurons to pure tones and amplitude-modulated (AM) tones were recorded and characterized as a function of modulation frequency. Hearing thresholds, spontaneous rate, and frequency tuning characteristics of IC neurons of bcan-/- mice were normal. Lack of brevican, however, led to shorter first spike latencies of neuronal responses at modulation frequencies ≥ 70 Hz and to two- to threefold evoked rates in response to AM tone stimulation. Surprisingly, the vector strength and the corresponding correlation coefficients of phase locking ≥ 50 Hz modulation frequency were increased in bcan-/- mice compared to bcan+/+ littermates.
Taken together, our results demonstrate that lack of the extracellular matrix protein brevican improves rather than impairs auditory processing of AM tones, which is puzzling. One limitation of our study is the systemic deletion of brevican. Future experiments using conditional, region-specific knockout mouse models would help to understand the effects of brevican in the auditory pathway in more detail.
This study was supported by DFG PP1608/2.