Low-threshold potassium currents stabilize IID-sensitivity in the inferior colliculus

The inferior colliculus (IC) is a midbrain nucleus that exhibits sensitivity to differences in interaural time and intensity (ITDs and IIDs) and integrates information from the auditory brainstem to provide an unambiguous representation of sound location across the azimuth. Further upstream, in the lateral superior olive (LSO), absence of low-threshold potassium currents in Kcna1[superscript −/−] mice interfered with response onset timing and restricted IID-sensitivity to the hemifield of the excitatory ear. Assuming the IID-sensitivity in the IC to be at least partly inherited from LSO neurons, the IC IID-encoding was compared between wild-type (Kcna1[superscript +/+]) and Kcna1[superscript −/−] mice. We asked whether the effect observed in the Kcna1[superscript −/−] LSO is (1) simply propagated into the IC, (2) is enhanced and amplified or, (3) alternatively, is compensated and so no longer detectable. Our results show that general IC response properties as well as the distribution of IID-functions were comparable in Kcna1[superscript −/−] and Kcna1[superscript+/+] mice. In agreement with the literature IC neurons exhibited a higher level-invariance of IID-sensitivity compared to LSO neurons. However, manipulating the timing between the inputs of the two ears caused significantly larger shifts of IID-sensitivity in Kcna1[superscript −/−] mice, whereas in the wild-type IC the IID functions were stable and less sensitive to changes of the temporal relationship between the binaural inputs. We conclude that the IC not only inherits IID-sensitivity from the LSO, but that the convergence with other, non-olivary inputs in the wild-type IC acts to quality-control, consolidate, and stabilize IID representation; this necessary integration of inputs is impaired in the absence of the low-threshold potassium currents mediated by Kv1.1

Early Postnatal Development of Spontaneous and Acoustically Evoked Discharge Activity of Principal Cells of the Medial Nucleus of the Trapezoid Body: An In Vivo Study in Mice

The calyx of Held synapse in the medial nucleus of the trapezoid body of the auditory brainstem has become an established in vitro model to study the development of fast glutamatergic transmission in the mammalian brain. However, we still lack in vivo data at this synapse on the maturation of spontaneous and sound-evoked discharge activity before and during the early phase of acoustically evoked signal processing (i.e., before and after hearing onset). Here we report in vivo single-unit recordings in mice from postnatal day 8 (P8) to P28 with a specific focus on developmental changes around hearing onset (P12). Data were obtained from two mouse strains commonly used in brain slice recordings: CBA/J and C57BL/6J. Spontaneous discharge rates progressively increased from P8 to P13, initially showing bursting patterns and large coefficients of variation (CVs), which changed to more continuous and random discharge activity accompanied by gradual decrease of CV around hearing onset. From P12 on, sound-evoked activity yielded phasic-tonic discharge patterns with discharge rates increasing up to P28. Response thresholds and shapes of tuning curves were adult-like by P14. A gradual shortening in response latencies was observed up to P18. The three-dimensional tonotopic organization of the medial nucleus of the trapezoid body yielded a high-to-low frequency gradient along the mediolateral and dorsoventral but not in the rostrocaudal axes. These data emphasize that models of signal transmission at the calyx of Held based on in vitro data have to take developmental changes in firing rates and response latencies up to the fourth postnatal week into account

Interaction of Excitation and Inhibition in Anteroventral Cochlear Nucleus Neurons That Receive Large Endbulb Synaptic Endings

Spherical bushy cells (SBCs) of the anteroventral cochlear nucleus (AVCN) receive their main excitatory input from auditory nerve fibers (ANFs) through large synapses, endbulbs of Held. These cells are also the target of inhibitory inputs whose function is not well understood. The present study examines the role of inhibition in the encoding of low-frequency sounds in the gerbil's AVCN. The presynaptic action potentials of endbulb terminals and postsynaptic action potentials of SBCs were monitored simultaneously in extracellular single-unit recordings in vivo. An input–output analysis of presynaptic and postsynaptic activity was performed for both spontaneous and acoustically driven activity. Two-tone stimulation and neuropharmacological experiments allowed the effects of neuronal inhibition and cochlear suppression on SBC activity to be distinguished. Ninety-one percent of SBCs showed significant neuronal inhibition. Inhibitory sidebands enclosed the high- or low-frequency, or both, sides of the excitatory areas of these units; this was reflected as a presynaptic to postsynaptic increase in frequency selectivity of up to one octave. Inhibition also affected the level-dependent responses at the characteristic frequency. Although in all units the presynaptic recordings showed monotonic rate-level functions, this was the case in only half of the postsynaptic recordings. In the other half of SBCs, postsynaptic inhibitory areas overlapped the excitatory areas, resulting in nonmonotonic rate-level functions. The results demonstrate that the sound-evoked spike activity of SBCs reflects the integration of acoustically driven excitatory and inhibitory input. The inhibition specifically affects the processing of the spectral, temporal, and intensity cues of acoustic signals

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

Responses to SAM.

<p>Synchronization indices (left column) and entrainment (right column) as a function of modulation frequency for the different PSTH types. The respective bottommost plots show the average transfer functions for each PSTH type. The horizontal line indicates the 0.3 cut-off criterion that was chosen to classify responses as being phase-locked. Note that C_S units show best and PL units worst ability to comodulate with fast fluctuations in stimulus amplitude.</p

Cluster analyses considering all evaluated response properties.

<p><b>A</b>: Dendrogram illustrating the result of hierarchical cluster analysis. The units (n = 233) are lined up at the bottom of the graph. The analysis suggests five clusters characterized by a specific distribution of parameter values. <b>B</b>: Mean of the respective parameter values for each property in the resulted clusters I–V. The values are standardized and normalized to the respective maxima (for original data and statistical analyses see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029965#pone-0029965-t002" target="_blank">table 2</a>). Note that for almost all individual properties significant differences exist between the clusters, and some properties also correlated across clusters. <b>C</b>: However, principal component analysis gives no indication for clearly separated groups of units, neither for the different clusters gathered from hierarchical cluster analysis (<b>C1</b>) nor for the different PSTH types (<b>C2</b>). In both cases units establishing different groups tend to accumulate in different regions of the plot. Still, the different groups strongly overlap, especially in the centre of the plot. Thus, with respect to their physiological properties the AVCN neurons form a continuum rather than distinct groups.</p

Cluster analyses based on a restricted set of parameters.

<p>See text for the reasons of the restriction. The parameter considered are indicated in B. Design of the graphs is the same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029965#pone-0029965-g006" target="_blank">figure 6</a>. <b>A</b>: The present cluster analysis suggests a distinction of four clusters (a–d) with <b>B</b>: specific properties. Note that there is some correspondence between this restricted analysis and the analysis given in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029965#pone-0029965-g006" target="_blank">figure 6:</a> Cluster ‘a’ relates to cluster V; ‘b’ to I, ‘c’ to II, and ‘d’ to IV. <b>C</b>: The principal component analysis arranges the units in one big coherent cluster. Units establishing different clusters (<b>C1</b>) and different PSTH types (<b>C2</b>) still could not be separated.</p

Physiological response properties of different clusters of AVCN units according to hierarchical cluster analysis using all evaluated properties.

<p>abbreviations explained in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029965#s2" target="_blank">methods</a>.</p><p>categorical values are described in text.</p>a<p>Means ± S.D./Median (25%, 75%).</p>b<p>cluster that do not significantly differ are within one parentheses.</p

Physiological response properties of different PSTH groups in AVCN.

<p>abbreviations explained in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029965#s2" target="_blank">methods</a>.</p><p>categorical values are described in text.</p>a<p>Means ± S.D./Median (25%, 75%).</p>b<p>PSTH groups that do not significantly differ are within one parentheses.</p

Principal component analysis employing three principal components and recheck of PSTH classification.

<p>Same sample of units (n = 174) and analysis as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029965#pone-0029965-g007" target="_blank">figure 7</a>. <b>A1</b>: Principal component analysis with assignment of the units to the different clusters gathered from hierarchical cluster analysis. <b>A2</b>: Principal component analysis with assignment of the units to the different PSTH types. Note that even a visualization based on the three dominant principal components does not indicate a clear separation of unit types. <b>B</b>: PSTHs of units in regions of the plot which are mainly occupied by other PSTH types, i.e. a PL_N (<b>B1</b>), a C_S (<b>B2</b>) and a unit which is not unambiguously to classify (<b>B3</b>). This unit was classified as C_T, but it could also be a PL.</p