Sound frequency affects the auditory motion-onset response in humans.

The current study examines the modulation of the motion-onset response based on the frequency-range of sound stimuli. Delayed motion-onset and stationary stimuli were presented in a free-field by sequentially activating loudspeakers on an azimuthal plane keeping the natural percept of externalized sound presentation. The sounds were presented in low- or high-frequency ranges and had different motion direction within each hemifield. Difference waves were calculated by contrasting the moving and stationary sounds to isolate the motion-onset responses. Analyses carried out at the peak amplitudes and latencies on the difference waves showed that the early part of the motion response (cN1) was modulated by the frequency range of the sounds with stronger amplitudes elicited by stimuli with high frequency range. Subsequent post hoc analysis of the normalized amplitude of the motion response confirmed the previous finding by excluding the possibility that the frequency range had an overall effect on the waveform, and showing that this effect was instead limited to the motion response. These results support the idea of a modular organization of the motion-onset response with the processing of primary sound motion characteristics being reflected in the early part of the response. Also, the article highlights the importance of specificity in auditory stimulus design.

Tonotopic action potential tuning of maturing auditory neurons through endogenous ATP.

KEY POINTS: Following the genetically controlled formation of neuronal circuits, early firing activity guides the development of sensory maps in the auditory, visual and somatosensory system. However, it is not clear whether the activity of central auditory neurons is specifically regulated depending on the position within the sensory map. In the ventral cochlear nucleus, the first central station along the auditory pathway, we describe a mechanism through which paracrine ATP signalling enhances firing in a cell-specific and tonotopically-determined manner. Developmental down-regulation of P2X2/3R currents along the tonotopic axis occurs simultaneously with an increase in AMPA receptor currents, suggesting a high-to-low frequency maturation pattern. Facilitated action potential (AP) generation, measured as higher firing rate, shorter EPSP-AP delay in vivo and shorter AP latency in slice experiments, is consistent with increased synaptic efficacy caused by ATP. The long lasting change in intrinsic neuronal excitability is mediated by the heteromeric P2X2/3 receptors. ABSTRACT: Synaptic refinement and strengthening are activity-dependent processes that establish orderly arranged cochleotopic maps throughout the central auditory system. The maturation of auditory brainstem circuits is guided by action potentials (APs) arising from the inner hair cells in the developing cochlea. The AP firing of developing central auditory neurons can be modulated by paracrine ATP signalling, as shown for the cochlear nucleus bushy cells and principal neurons in the medial nucleus of the trapezoid body. However, it is not clear whether neuronal activity may be specifically regulated with respect to the nuclear tonotopic position (i.e. sound frequency selectivity). Using slice recordings before hearing onset and in vivo recordings with iontophoretic drug applications after hearing onset, we show that cell-specific purinergic modulation follows a precise tonotopic pattern in the ventral cochlear nucleus of developing gerbils. In high-frequency regions, ATP responsiveness diminished before hearing onset. In low-to-mid frequency regions, ATP modulation persisted after hearing onset in a subset of low-frequency bushy cells (characteristic frequency< 10 kHz). Down-regulation of P2X2/3R currents along the tonotopic axis occurs simultaneously with an increase in AMPA receptor currents, thus suggesting a high-to-low frequency maturation pattern. Facilitated AP generation, measured as higher firing frequency, shorter EPSP-AP delay in vivo, and shorter AP latency in slice experiments, is consistent with increased synaptic efficacy caused by ATP. Finally, by combining recordings and pharmacology in vivo, in slices, and in human embryonic kidney 293 cells, it was shown that the long lasting change in intrinsic neuronal excitability is mediated by the P2X2/3R.

Inhibition shapes acoustic responsiveness in spherical bushy cells.

Signal processing in the auditory brainstem is based on an interaction of neuronal excitation and inhibition. To date, we have incomplete knowledge of how the dynamic interplay of both contributes to the processing power and temporal characteristics of signal coding. The spherical bushy cells (SBCs) of the anteroventral cochlear nucleus (AVCN) receive their primary excitatory input through auditory nerve fibers via large, axosomatic synaptic terminals called the endbulbs of Held and by additional, acoustically driven inhibitory inputs. SBCs provide the input to downstream nuclei of the brainstem sound source localization circuitry, such as the medial and lateral superior olive, which rely on temporal precise inputs. In this study, we used juxtacellular recordings in anesthetized Mongolian gerbils to assess the effect of acoustically evoked inhibition on the SBCs input-output function and on temporal precision of SBC spiking. Acoustically evoked inhibition proved to be strong enough to suppress action potentials (APs) of SBCs in a stimulus-dependent manner. Inhibition shows slow onset and offset dynamics and increasing strength at higher sound intensities. In addition, inhibition decreases the rising slope of the EPSP and prolongs the EPSP-to-AP transition time. Both effects can be mimicked by iontophoretic application of glycine. Inhibition also improves phase locking of SBC APs to low-frequency tones by acting as a gain control to suppress poorly timed EPSPs from generating postsynaptic APs to maintain precise SBC spiking across sound intensities. The present data suggest that inhibition substantially contributes to the processing power of second-order neurons in the ascending auditory system.

Subdivision of Broca's region based on individual-level functional connectivity.

Broca's region is composed of two adjacent cytoarchitectonic areas, 44 and 45, which have distinct connectivity to superior temporal and inferior parietal regions in both macaque monkeys and humans. The current study aimed to make use of prior knowledge of sulcal anatomy and resting-state functional connectivity, together with a novel visualization technique, to manually parcellate areas 44 and 45 in individual brains in vivo. One hundred and one resting-state functional magnetic resonance imaging datasets from the Human Connectome Project were used. Left-hemisphere surface-based correlation matrices were computed and visualized in brainGL. By observation of differences in the connectivity patterns of neighbouring nodes, areas 44 and 45 were manually parcellated in individual brains, and then compared at the group-level. Additionally, the manual labelling approach was compared with parcellation results based on several data-driven clustering techniques. Areas 44 and 45 could be clearly distinguished from each other in all individuals, and the manual segmentation method showed high test-retest reliability. Group-level probability maps of areas 44 and 45 showed spatial consistency across individuals, and corresponded well to cytoarchitectonic probability maps. Group-level connectivity maps were consistent with previous studies showing distinct connectivity patterns of areas 44 and 45. Data-driven parcellation techniques produced clusters with varying degrees of spatial overlap with the manual labels, indicating the need for further investigation and validation of machine learning cortical segmentation approaches. The current study provides a reliable method for individual-level cortical parcellation that could be applied to regions distinguishable by even the most subtle differences in patterns of functional connectivity.

Dynamic fidelity control to the central auditory system: synergistic glycine/GABAergic inhibition in the cochlear nucleus.

GABA and glycine are the major inhibitory transmitters that attune neuronal activity in the CNS of mammals. The respective transmitters are mostly spatially separated, that is, synaptic inhibition in the forebrain areas is mediated by GABA, whereas glycine is predominantly used in the brainstem. Accordingly, inhibition in auditory brainstem circuits is largely mediated by glycine, but there are few auditory synapses using both transmitters in maturity. Little is known about physiological advantages of such a two-transmitter inhibitory mechanism. We explored the benefit of engaging both glycine and GABA with inhibition at the endbulb of Held-spherical bushy cell synapse in the auditory brainstem of juvenile Mongolian gerbils. This model synapse enables selective in vivo activation of excitatory and inhibitory neuronal inputs through systemic sound stimulation and precise analysis of the input (endbulb of Held) output (spherical bushy cell) function. The combination of in vivo and slice electrophysiology revealed that the dynamic AP inhibition in spherical bushy cells closely matches the inhibitory conductance profile determined by the glycine-R and GABAA-R. The slow and potent glycinergic component dominates the inhibitory conductance, thereby primarily accounting for its high-pass filter properties. GABAergic transmission enhances the inhibitory strength and shapes its duration in an activity-dependent manner, thus increasing the inhibitory potency to suppress the excitation through the endbulb of Held. Finally, in silico modeling provides a strong link between in vivo and slice data by simulating the interactions between the endbulb- and the synergistic glycine-GABA-conductances during in vivo-like spontaneous and sound evoked activities.

α2δ3 is essential for normal structure and function of auditory nerve synapses and is a novel candidate for auditory processing disorders.

The auxiliary subunit α2δ3 modulates the expression and function of voltage-gated calcium channels. Here we show that α2δ3 mRNA is expressed in spiral ganglion neurons and auditory brainstem nuclei and that the protein is required for normal acoustic responses. Genetic deletion of α2δ3 led to impaired auditory processing, with reduced acoustic startle and distorted auditory brainstem responses. α2δ3(-/-) mice learned to discriminate pure tones, but they failed to discriminate temporally structured amplitude-modulated tones. Light and electron microscopy analyses revealed reduced levels of presynaptic Ca(2+) channels and smaller auditory nerve fiber terminals contacting cochlear nucleus bushy cells. Juxtacellular in vivo recordings of sound-evoked activity in α2δ3(-/-) mice demonstrated impaired transmission at these synapses. Together, our results identify a novel role for the α2δ3 auxiliary subunit in the structure and function of specific synapses in the mammalian auditory pathway and in auditory processing disorders.

The extracellular matrix molecule brevican is an integral component of the machinery mediating fast synaptic transmission at the calyx of Held.

KEY POINTS: The proteoglycan brevican is a major component of the extracellular matrix of perineuronal nets and is highly enriched in the perisynaptic space suggesting a role for synaptic transmission. We have introduced the calyx of Held in the auditory brainstem as a model system to study the impact of brevican on dynamics and reliability of synaptic transmission. In vivo extracellular single-unit recordings at the calyx of Held in brevican-deficient mice yielded a significant increase in the action potential (AP) transmission delay and a prolongation of pre- and postsynaptic APs. The changes in dynamics of signal transmission were accompanied by the reduction of presynaptic vGlut1 and ultrastructural changes in the perisynaptic space. These data show that brevican is an important mediator of fast synaptic transmission at the calyx of Held. ABSTRACT: The extracellular matrix is an integral part of the neural tissue. Its most conspicuous manifestation in the brain are the perineuronal nets (PNs) which surround somata and proximal dendrites of distinct neuron types. The chondroitin sulfate proteoglycan brevican is a major component of PNs. In contrast to other PN-comprising proteoglycans (e.g. aggrecan and neurocan), brevican is mainly expressed in the perisynaptic space closely associated with both the pre- and postsynaptic membrane. This specific localization prompted the hypothesis that brevican might play a role in synaptic transmission. In the present study we specifically investigated the role of brevican in synaptic transmission at a central synapse, the calyx of Held in the medial nucleus of the trapezoid body, by the use of in vivo electrophysiology, immunohistochemistry, biochemistry and electron microscopy. In vivo extracellular single-unit recordings were acquired in brevican-deficient mice and the dynamics and reliability of synaptic transmission were compared to wild-type littermates. In knockout mice, the speed of pre-to-postsynaptic action potential (AP) transmission was reduced and the duration of the respective pre- and postsynaptic APs increased. The reliability of signal transmission, however, was not affected by the lack of brevican. The changes in dynamics of signal transmission were accompanied by the reduction of (i) presynaptic vGlut1 and (ii) the size of subsynaptic cavities. The present results suggest an essential role of brevican for the functionality of high-speed synaptic transmission at the calyx of Held.

Age-related changes in sound localisation ability.

Auditory spatial processing is an important ability in everyday life and allows the processing of omnidirectional information. In this review, we report and compare data from psychoacoustic and electrophysiological experiments on sound localisation accuracy and auditory spatial discrimination in infants, children, and young and older adults. The ability to process auditory spatial information changes over lifetime: the perception of the acoustic space develops from an initially imprecise representation in infants and young children to a concise representation of spatial positions in young adults and the respective performance declines again in older adults. Localisation accuracy shows a strong deterioration in older adults, presumably due to declined processing of binaural temporal and monaural spectro-temporal cues. When compared to young adults, the thresholds for spatial discrimination were strongly elevated both in young children and older adults. Despite the consistency of the measured values the underlying causes for the impaired performance might be different: (1) the effect is due to reduced cognitive processing ability and is thus task-related; (2) the effect is due to reduced information about the auditory space and caused by declined processing in auditory brain stem circuits; and (3) the auditory space processing regime in young children is still undergoing developmental changes and the interrelation with spatial visual processing is not yet established. In conclusion, we argue that for studying auditory space processing over the life course, it is beneficial to investigate spatial discrimination ability instead of localisation accuracy because it more reliably indicates changes in the processing ability.

Free-field study on auditory localization and discrimination performance in older adults.

Localization accuracy and acuity for low- (0.375-0.75 kHz; LN) and high-frequency (2.25-4.5 kHz; HN) noise bands were examined in young (20-29 years) and older adults (65-83 years) in the acoustic free-field. A pointing task was applied to quantify accuracy, while acuity was inferred from minimum audible angle (MAA) thresholds measured with an adaptive 3-alternative forced-choice procedure. Accuracy decreased with laterality and age. From young to older adults, the accuracy declined by up to 23 % for the low-frequency noise band across all lateralities. The mean age effect was even more pronounced on MAA thresholds. Thus, age was a strong predictor for MAA thresholds for both LN and HN bands. There was no significant correlation between hearing status and localization performance. These results suggest that central auditory processing of space declines with age and is mainly driven by age-related changes in the processing of binaural cues (interaural time difference and interaural intensity difference) and not directly induced by peripheral hearing loss. We conclude that the representation of the location of sound sources becomes blurred with age as a consequence of declined temporal processing, the effect of which becomes particularly evident for MAA thresholds, where two closely adjoining sound sources have to be separated. While localization accuracy and MAA were not correlated in older adults, only a weak correlation was found in young adults. These results point to an employment of different processing strategies for localization accuracy and acuity.

Purinergic modulation of neuronal activity in developing auditory brainstem.

In the developing nervous system, spontaneous neuronal activity arises independently of experience or any environmental input. This activity may play a major role in axonal pathfinding, refinement of topographic maps, dendritic morphogenesis, and the segregation of axonal terminal arbors. In the auditory system, endogenously released ATP in the cochlea activates inner hair cells to trigger bursts of action potentials (APs), which are transferred to the central auditory system. Here we show the modulatory role of purinergic signaling beyond the cochlea, i.e., the developmentally regulated and cell-type-specific depolarizing effects on auditory brainstem neurons of Mongolian gerbil. We assessed the effects of P2X receptors (P2XRs) on neuronal excitability from prehearing to early stages of auditory signal processing. Our results demonstrate that in neurons expressing P2XRs, extracellular ATP can evoke APs in sync with Ca(2+) signals. In cochlear nucleus (CN) bushy cells, ATP increases spontaneous and also acoustically evoked activity in vivo, but these effects diminish with maturity. Moreover, ATP not only augmented glutamate-driven firing, but it also evoked APs in the absence of glutamatergic transmission. In vivo recordings also revealed that endogenously released ATP in the CN contributes to neuronal firing activity by facilitating AP generation and prolonging AP duration. Given the enhancing effect of ATP on AP firing and confinement of P2XRs to certain auditory brainstem nuclei, and to distinct neurons within these nuclei, it is conceivable that purinergic signaling plays a specific role in the development of neuronal brainstem circuits.

The calyx of Held develops adult-like dynamics and reliability by hearing onset in the mouse in vivo.

The development of the auditory system has received increasing attention since the mechanisms of patterned, spontaneous activity in prehearing mammals were discovered. This early activity originates in the cochlea and is assumed to be of importance for the establishment and refinement of synaptic connections in the auditory system. In the present study we investigate synaptic transmission and its interplay with spontaneous discharges in the developing auditory system. We used the calyx of Held as a model system, where this question can be investigated in vivo over a broad range of ages [postnatal day 8 (P8)-P28]. To precisely quantify the timing and reliability of synaptic transmission, we developed a novel fitting approach which decomposes the extracellularly recorded signal into its presynaptic and postsynaptic components. In prehearing mice, we found signal transmission to be unreliable, with high variability in the transmission delay and in the amplitude of postsynaptic components. These timing and amplitude changes were strongly correlated with the preceding activity. Around hearing onset (P12-P14), the properties of signal transmission converged to the adult-like state which was characterized by high transmission reliability as well as high consistency in timing and amplitude. Although activity-dependent depression was still found in action potentials, EPSP depression no longer played a prominent role. In conclusion, the maturation of synaptic transmission at the calyx of Held seems to be precisely timed to achieve its adult potential by the time acoustically evoked signal processing commences.

The Cl--channel TMEM16A is involved in the generation of cochlear Ca2+ waves and promotes the refinement of auditory brainstem networks in mice.

Before hearing onset (postnatal day 12 in mice), inner hair cells (IHCs) spontaneously fire action potentials, thereby driving pre-sensory activity in the ascending auditory pathway. The rate of IHC action potential bursts is modulated by inner supporting cells (ISCs) of Kölliker's organ through the activity of the Ca2+-activated Cl--channel TMEM16A (ANO1). Here, we show that conditional deletion of Ano1 (Tmem16a) in mice disrupts Ca2+ waves within Kölliker's organ, reduces the burst-firing activity and the frequency selectivity of auditory brainstem neurons in the medial nucleus of the trapezoid body (MNTB), and also impairs the functional refinement of MNTB projections to the lateral superior olive. These results reveal the importance of the activity of Kölliker's organ for the refinement of central auditory connectivity. In addition, our study suggests the involvement of TMEM16A in the propagation of Ca2+ waves, which may also apply to other tissues expressing TMEM16A.

Low-voltage activated Kv1.1 subunits are crucial for the processing of sound source location in the lateral superior olive in mice.

Voltage-gated potassium (Kv) channels containing Kv1.1 subunits are strongly expressed in neurons that fire temporally precise action potentials (APs). In the auditory system, AP timing is used to localize sound sources by integrating interaural differences in time (ITD) and intensity (IID) using sound arriving at both cochleae. In mammals, the first nucleus to encode IIDs is the lateral superior olive (LSO), which integrates excitation from the ipsilateral ventral cochlear nucleus and contralateral inhibition mediated via the medial nucleus of the trapezoid body. Previously we reported that neurons in this pathway show reduced firing rates, longer latencies and increased jitter in Kv1.1 knockout (Kcna1−/−) mice. Here, we investigate whether these differences have direct impact on IID processing by LSO neurons. Single-unit recordings were made from LSO neurons of wild-type (Kcna1+/+) and from Kcna1−/− mice. IID functions were measured to evaluate genotype-specific changes in integrating excitatory and inhibitory inputs. In Kcna1+/+ mice, IID sensitivity ranged from +27 dB (excitatory ear more intense) to −20 dB (inhibitory ear more intense), thus covering the physiologically relevant range of IIDs. However, the distribution of IID functions in Kcna1−/− mice was skewed towards positive IIDs, favouring ipsilateral sound positions. Our computational model revealed that the reduced performance of IID encoding in the LSO of Kcna1−/− mice is mainly caused by a decrease in temporal fidelity along the inhibitory pathway. These results imply a fundamental role for Kv1.1 in temporal integration of excitation and inhibition during sound source localization.

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.

Presynaptic and postsynaptic origin of multicomponent extracellular waveforms at the endbulb of Held-spherical bushy cell synapse.

Extracellular signals from the endbulb of Held-spherical bushy cell (SBC) synapse exhibit up to three component waves ('P', 'A' and 'B'). Signals lacking the third component (B) are frequently observed but as the origin of each of the components is uncertain, interpretation of this lack of B has been controversial: is it a failure to release transmitter or a failure to generate or propagate an action potential? Our aim was to determine the origin of each component. We combined single- and multiunit in vitro methods in Mongolian gerbils and Wistar rats and used pharmacological tools to modulate glutamate receptors or voltage-gated sodium channels. Simultaneous extra- and intracellular recordings from single SBCs demonstrated a presynaptic origin of the P-component, consistent with data obtained with multielectrode array recordings of local field potentials. The later components (A and B) correspond to the excitatory postsynaptic potential (EPSP) and action potential of the SBC, respectively. These results allow a clear interpretation of in vivo extracellular signals. We conclude that action potential failures occurring at the endbulb-SBC synaptic junction largely reflect failures of the EPSP to trigger an action potential and not failures of synaptic transmission. The data provide the basis for future investigation of convergence of excitatory and inhibitory inputs in modulating transmission at a fully functional neuronal system using physiological stimulation.

Spatial selective attention in a complex auditory environment such as polyphonic music.

To investigate the influence of spatial information in auditory scene analysis, polyphonic music (three parts in different timbres) was composed and presented in free field. Each part contained large falling interval jumps in the melody and the task of subjects was to detect these events in one part ("target part") while ignoring the other parts. All parts were either presented from the same location (0 degrees; overlap condition) or from different locations (-28 degrees, 0 degrees, and 28 degrees or -56 degrees, 0 degrees, and 56 degrees in the azimuthal plane), with the target part being presented either at 0 degrees or at one of the right-sided locations. Results showed that spatial separation of 28 degrees was sufficient for a significant improvement in target detection (i.e., in the detection of large interval jumps) compared to the overlap condition, irrespective of the position (frontal or right) of the target part. A larger spatial separation of the parts resulted in further improvements only if the target part was lateralized. These data support the notion of improvement in the suppression of interfering signals with spatial sound source separation. Additionally, the data show that the position of the relevant sound source influences auditory performance.

Orienting asymmetries and lateralized processing of sounds in humans.

BACKGROUND: Lateralized processing of speech is a well studied phenomenon in humans. Both anatomical and neurophysiological studies support the view that nonhuman primates and other animal species also reveal hemispheric differences in areas involved in sound processing. In recent years, an increasing number of studies on a range of taxa have employed an orienting paradigm to investigate lateralized acoustic processing. In this paradigm, sounds are played directly from behind and the direction of turn is recorded. This assay rests on the assumption that a hemispheric asymmetry in processing is coupled to an orienting bias towards the contralateral side. To examine this largely untested assumption, speech stimuli as well as artificial sounds were presented to 224 right-handed human subjects shopping in supermarkets in Germany and in the UK. To verify the lateralized processing of the speech stimuli, we additionally assessed the brain activation in response to presentation of the different stimuli using functional magnetic resonance imaging (fMRI). RESULTS: In the naturalistic behavioural experiments, there was no difference in orienting behaviour in relation to the stimulus material (speech, artificial sounds). Contrary to our predictions, subjects revealed a significant left bias, irrespective of the sound category. This left bias was slightly but not significantly stronger in German subjects. The fMRI experiments confirmed that the speech stimuli evoked a significant left lateralized activation in BA44 compared to the artificial sounds. CONCLUSION: These findings suggest that in adult humans, orienting biases are not necessarily coupled with lateralized processing of acoustic stimuli. Our results -- as well as the inconsistent orienting biases found in different animal species -- suggest that the orienting assay should be used with caution. Apparently, attention biases, experience, and experimental conditions may all affect head turning responses. Because of the complexity of the interaction of factors, the use of the orienting assay to determine lateralized processing of sound stimuli is discouraged.

Functional Development of Principal Neurons in the Anteroventral Cochlear Nucleus Extends Beyond Hearing Onset.

Sound information is transduced into graded receptor potential by cochlear hair cells and encoded as discrete action potentials of auditory nerve fibers. In the cochlear nucleus, auditory nerve fibers convey this information through morphologically distinct synaptic terminals onto bushy cells (BCs) and stellate cells (SCs) for processing of different sound features. With expanding use of transgenic mouse models, it is increasingly important to understand the in vivo functional development of these neurons in mice. We characterized the maturation of spontaneous and acoustically evoked activity in BCs and SCs by acquiring single-unit juxtacellular recordings between hearing onset (P12) and young adulthood (P30) of anesthetized CBA/J mice. In both cell types, hearing sensitivity and characteristic frequency (CF) range are mostly adult-like by P14, consistent with rapid maturation of the auditory periphery. In BCs, however, some physiological features like maximal firing rate, dynamic range, temporal response properties, recovery from post-stimulus depression, first spike latency (FSL) and encoding of sinusoid amplitude modulation undergo further maturation up to P18. In SCs, the development of excitatory responses is even more prolonged, indicated by a gradual increase in spontaneous and maximum firing rates up to P30. In the same cell type, broadly tuned acoustically evoked inhibition is immediately effective at hearing onset, covering the low- and high-frequency flanks of the excitatory response area. Together, these data suggest that maturation of auditory processing in the parallel ascending BC and SC streams engages distinct mechanisms at the first central synapses that may differently depend on the early auditory experience.

The medial nucleus of the trapezoid body in rat: spectral and temporal properties vary with anatomical location of the units.

The medial nucleus of the trapezoid body (MNTB) is a distinct nucleus in the superior olivary complex that transforms excitatory input from the cochlear nucleus into a widespread inhibitory output to distinct auditory brainstem nuclei. Few studies have dealt with the response properties of MNTB neurons to sound stimulation using in vivo preparations. In order to have a better understanding of the functional significance of the MNTB in auditory processing we report the basic temporal and spectral response properties of its principal cells using single-unit extracellular recordings to acoustic stimulation with pure tones and amplitude-modulated stimuli in the rat. Ninety-seven per cent of units showed V-shaped frequency response areas. Rate level functions were mainly saturating (51%) or monotonic (45%) at high intensities. Post-stimulus time histograms typically were characterised as primary-like with notch (59%) or primary-like (33%). Units showed good phase-locking to sinusoidally amplitude-modulated signals with vector strength VS values up to 0.87. Modulation transfer functions had low-pass shapes at near-threshold levels, with cut-off frequencies ranging from 370 to 1270 Hz. Exploration of the relationship between the temporal and spectral properties and the location of the units in the MNTB yielded characteristic frequency (CF)-dependent response properties (latency, Q(10) and cut-off frequency) following a medio-lateral gradient, and CF-independent response features (maximum firing rate) following a dorso-ventral gradient.

Dynamic coupling of excitatory and inhibitory responses in the medial nucleus of the trapezoid body.

The neuronal representation of acoustic amplitude modulations is an important prerequisite for understanding the processing of natural sounds. We investigated this representation in the medial nucleus of the trapezoid body (MNTB) of the Mongolian gerbil using sinusoidal amplitude modulations (SAM). Depending on the SAM's carrier frequency (f(C)) MNTB cells either increase or decrease their discharge rates, indicating underlying excitatory and inhibitory/suppressive mechanisms. As natural sounds typically are composed of multiple spectral components we investigated how stimuli containing two spectral components are represented in the MNTB, especially when they have opposing effects on the discharge rate. Three conditions were compared: SAM stimuli (1) with rate-increasing f(C), (2) with rate-increasing f(C) and an additional unmodulated rate-decreasing pure tone, and (3) with rate-decreasing f(C) and an unmodulated, rate-increasing pure tone. We found that responses under all three conditions showed comparable strength of phase-locking. Adding a rate-decreasing tone to a rate-increasing SAM increased phase-locking for modulation frequencies (f(AM)) of < or = 600 Hz. A comparison of two possible coding strategies--phase-locking vs. envelope reproduction--indicates that both strategies are realized to different degrees depending on the f(AM). We measured latencies for following modulations in rate-increasing and rate-decreasing SAMs using a modified reverse correlation approach. Although latencies varied between 2.5 and 5 ms between cells, a decrease in rate consistently followed an increase in rate with a delay of about 0.2 ms in each cell. These results suggest a temporally precise representation of rate-increasing and rate-decreasing stimuli at the level of the MNTB during dynamic stimulation.