The absence of brain-specific link protein Bral2 in perineuronal nets hampers auditory temporal resolution and neural adaptation in mice

Physiol Res. 2017 Nov 24;66(5):867-880. doi: 10.33549/physiolres.933605. Epub 2017 Oct 11.


Brain-specific link protein Bral2 represents a substantial component of perineuronal nets (PNNs) enwrapping neurons in the central nervous system. To elucidate the role of Bral2 in auditory signal processing, the hearing function in knockout Bral2(-/-) (KO) mice was investigated using behavioral and electrophysiological methods and compared with wild type Bral2(+/+) (WT) mice. The amplitudes of the acoustic startle reflex (ASR) and the efficiency of the prepulse inhibition of ASR (PPI of ASR), produced by prepulse noise stimulus or gap in continuous noise, was similar in 2-week-old WT and KO mice. Over the 2-month postnatal period the increase of ASR amplitudes was significantly more evident in WT mice than in KO mice. The efficiency of the PPI of ASR significantly increased in the 2-month postnatal period in WT mice, whereas in KO mice the PPI efficiency did not change. Hearing thresholds in 2-month-old WT mice, based on the auditory brainstem response (ABR) recordings, were significantly lower at high frequencies than in KO mice. However, amplitudes and peak latencies of individual waves of click-evoked ABR did not differ significantly between WT and KO mice. Temporal resolution and neural adaptation were significantly better in 2-month-old WT mice than in age-matched KO mice. These results support a hypothesis that the absence of perineuronal net formation at the end of the developmental period in the KO mice results in higher hearing threshold at high frequencies and weaker temporal resolution ability in adult KO animals compared to WT mice.

MeSH terms

  • Acoustic Stimulation / methods*
  • Adaptation, Physiological / physiology*
  • Age Factors
  • Animals
  • Evoked Potentials, Auditory, Brain Stem / physiology
  • Extracellular Matrix Proteins / deficiency*
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Net / growth & development
  • Nerve Net / metabolism*
  • Nerve Tissue Proteins / deficiency*
  • Peripheral Nerves / growth & development
  • Peripheral Nerves / metabolism
  • Prepulse Inhibition / physiology*
  • Reflex, Startle / physiology*
  • Time Factors


  • Extracellular Matrix Proteins
  • Hapln4 protein, mouse
  • Nerve Tissue Proteins