Nonselective TRPC channel inhibition and suppression of aminoglycoside-induced premature termination codon readthrough by the small molecule AC1903.

Nonsense mutations, which occur in ∼11% of patients with genetic disorders, introduce premature termination codons (PTCs) that lead to truncated proteins and promote nonsense-mediated mRNA decay. Aminoglycosides such as G418 permit PTC readthrough and so may be used to address this problem. However, their effects are variable between patients, making clinical use of aminoglycosides challenging.

Kv3.1 and Kv3.3 subunits differentially contribute to Kv3 channels and action potential repolarization in principal neurons of the auditory brainstem.

Key Points: Kv3.1 and Kv3.3 subunits are highly expressed in the auditory brainstem, with little or no mRNA for Kv3.

Acoustic trauma slows AMPA receptor-mediated EPSCs in the auditory brainstem, reducing GluA4 subunit expression as a mechanism to rescue binaural function.

Key Points: Lateral superior olive (LSO) principal neurons receive AMPA receptor (AMPAR) - and NMDA receptor (NMDAR)-mediated EPSCs and glycinergic IPSCs. Both EPSCs and IPSCs have slow kinetics in prehearing animals, which during developmental maturation accelerate to sub-millisecond decay time-constants. This correlates with a change in glutamate and glycine receptor subunit composition quantified via mRNA levels.

Subcortical neural synchrony and absolute thresholds predict frequency discrimination independently.

The neural mechanisms of pitch coding have been debated for more than a century. The two main mechanisms are coding based on the profiles of neural firing rates across auditory nerve fibers with different characteristic frequencies (place-rate coding), and coding based on the phase-locked temporal pattern of neural firing (temporal coding). Phase locking precision can be partly assessed by recording the frequency-following response (FFR), a scalp-recorded electrophysiological response that reflects synchronous activity in subcortical neurons.