Decreased temporal precision of auditory signaling in Kcna1-null mice: an electrophysiological study in vivo.

The voltage-gated potassium (Kv) channel subunit Kv1.1, encoded by the Kcna1 gene, is expressed strongly in the ventral cochlear nucleus (VCN) and the medial nucleus of the trapezoid body (MNTB) of the auditory pathway. To examine the contribution of the Kv1.1 subunit to the processing of auditory information, in vivo single-unit recordings were made from VCN neurons (bushy cells), axonal endings of bushy cells at MNTB cells (calyces of Held), and MNTB neurons of Kcna1-null (-/-) mice and littermate control (+/+) mice. Thresholds and spontaneous firing rates of VCN and MNTB neurons were not different between genotypes. At higher sound intensities, however, evoked firing rates of VCN and MNTB neurons were significantly lower in -/- mice than +/+ mice. The SD of the first-spike latency (jitter) was increased in VCN neurons, calyces, and MNTB neurons of -/- mice compared with +/+ controls. Comparison along the ascending pathway suggests that the increased jitter found in -/- MNTB responses arises mostly in the axons of VCN bushy cells and/or their calyceal terminals rather than in the MNTB neurons themselves. At high rates of sinusoidal amplitude modulations, -/- MNTB neurons maintained high vector strength values but discharged on significantly fewer cycles of the amplitude-modulated stimulus than +/+ MNTB neurons. These results indicate that in Kcna1-null mice the absence of the Kv1.1 subunit results in a loss of temporal fidelity (increased jitter) and the failure to follow high-frequency amplitude-modulated sound stimulation in vivo.

The medial nucleus of the trapezoid body in the gerbil is more than a relay: comparison of pre- and postsynaptic activity.

The medial nucleus of the trapezoid body (MNTB) plays an important role in the processing of interaural intensity differences, a feature that is critical for the localization of sound sources. It is generally believed that the MNTB functions primarily as a passive relay in converting excitatory input originating from the contralateral cochlear nucleus (CN) into an inhibitory input to the ipsilateral lateral superior olive. However, studies showing that the MNTB itself is also the target of inhibitory input suggest that the MNTB may serve more than a sign-converting function. To examine the fidelity of signal transmission at the CN-MNTB synapse, presynaptic calyceal potentials ("prepotentials"), reflecting the excitatory input to the MNTB neuron, and postsynaptic action potentials were simultaneously monitored with the same electrode during in vivo extracellular recordings from the gerbil's MNTB. Presynaptic activity differed from postsynaptic activity in several respects: (1) Spontaneous and sound-evoked discharge rates were greater presynaptically than postsynaptically. (2) Frequency tuning was sharper postsynaptically than presynaptically. (3) Calyceal terminals and MNTB neurons both showed phasic-tonic response patterns to tonal stimulation, but the duration of the onset response and the level of the tonic component were reduced postsynaptically. (4) Phase-locking to sound frequencies up to 1 kHz was greater postsynaptically than presynaptically. (5) The rate-intensity characteristics of pre- and postsynaptic activities differed significantly from each other in half of the MNTB neurons. To test the hypothesis that acoustically evoked inhibition of MNTB neurons contributed to the relatively lower levels of postsynaptic discharge, two-tone stimulation was applied, wherein the response to one tone-burst, set at the neuron's characteristic frequency, can be reduced by addition of a second "inhibitory" tone. The inhibitory tone caused a much larger reduction in post- than in presynaptic activity, indicating an acoustically evoked inhibitory influence directly on MNTB units. These findings show that transmission at the CN-MNTB synapse does not occur in a fixed one-to-one manner and that the response of MNTB neurons reflects the integration of their excitatory and inhibitory inputs.