Sandra Tolnai

The medial nucleus of the trapezoid body: comparative physiology.

Principal cells of the medial nucleus of the trapezoid body (MNTB) receive their excitatory input through large somatic terminals, the calyces of Held, which arise from axons of globular bushy cells located in the contralateral ventral cochlear nucleus. Discharges of MNTB neurons are characterized by high stimulus evoked firing rates, temporally precise onset responses, and a high degree of phase-locking to either pure tones or stimulus envelopes. Since the calyx of Held synapse is accessible to in vitro and to in vivo recordings, it serves as one of the most elaborate models for studying synaptic transmission in the mammalian brain. Although in such studies, the major emphasis is on synaptic physiology, the interpretation of the data will benefit from an understanding of the MNTBs contribution to auditory signal processing, including possible functional differences in different species. This implies the consideration of possible functional differences in different species. Here, we compare single unit recordings from MNTB principal cells in vivo in three different rodent species: gerbil, mouse and rat. Because of their good low-frequency hearing gerbils are often used in in vivo preparations, while mice and rats are predominantly used in slice preparations. We show that MNTB units in all three species exhibit high firing rates and precise onset-timing. Still there are species-specific specializations that might suggest the preferential use of one species over the others, depending on the scope of the respective investigation.

Spike Transmission Delay at the Calyx of Held In Vivo: Rate Dependence, Phenomenological Modeling, and Relevance for Sound Localization

Transmission at central synapses exhibits rapid changes in response amplitude under different patterns of stimulation. Whether the delay associated with the transmission of action potentials is similarly modifiable is important for temporally precise computations. We address this question at the calyx of Held of the medial nucleus of the trapezoid body (MNTB) in Mongolian gerbils in vivo using extracellular recordings. Here the pre- and postsynaptic activity can be observed simultaneously, allowing the definition of an action potential transmission delay (ATD) from the pre- to the postsynaptic side. We find the ATD to increase as a function of spike rate (10-40%). The temporal dynamics of the ATD increase exhibit an exponential shape with activity-dependent time constants ( approximately 15-25 ms). Recovery dynamics of ATD were mono- (20-70 ms) or biexponential with fast (3-20 ms) and slow time constants (50-500 ms). Using a phenomenological model to capture ATD dynamics, we estimated DeltaATD = 5-30 micros per transmitted action potential. Using vocalizations and cage noise stimuli, we confirm that substantial changes in ATD occur in natural situations. Because the ATD changes cover the behaviorally relevant range of interaural time differences in gerbils, these results could provide constraints for models of sound localization.

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 (fC) 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 fC, (2) with rate‐increasing fC and an additional unmodulated rate‐decreasing pure tone, and (3) with rate‐decreasing fC 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 (fAM) of ≤ 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 fAM. 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.

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, Q10 and cut‐off frequency) following a medio‐lateral gradient, and CF‐independent response features (maximum firing rate) following a dorso‐ventral gradient.

Multilinear models of single cell responses in the medial nucleus of the trapezoid body

The representation of acoustic stimuli in the brainstem forms the basis for higher auditory processing. While some characteristics of this representation (e.g. tuning curve) are widely accepted, it remains a challenge to predict the firing rate at high temporal resolution in response to complex stimuli. In this study we explore models for in vivo, single cell responses in the medial nucleus of the trapezoid body (MNTB) under complex sound stimulation. We estimate a family of models, the multilinear models, encompassing the classical spectrotemporal receptive field and allowing arbitrary input-nonlinearities and certain multiplicative interactions between sound energy and its short-term auditory context. We compare these to models of more traditional type, and also evaluate their performance under various stimulus representations. Using the context model, 75% of the explainable variance could be predicted based on a cochlear-like, gamma-tone stimulus representation. The presence of multiplicative contextual interactions strongly reduces certain inhibitory/suppressive regions of the linear kernels, suggesting an underlying nonlinear mechanism, e.g. cochlear or synaptic suppression, as the source of the suppression in MNTB neuronal responses. In conclusion, the context model provides a rich and still interpretable extension over many previous phenomenological models for modeling responses in the auditory brainstem at submillisecond resolution.

Binaural cues provide for a release from informational masking.

Informational masking (IM) describes the insensitivity of detecting a change in sound features in a complex acoustical environment when such a change could easily be detected in the absence of distracting sounds. IM occurs because of the similarity between deviant sound and distracting sounds (so-called similarity-based IM) and/or stimulus uncertainty stemming from trial-to-trial variability (so-called uncertainty-based IM). IM can be abolished if similarity-based or uncertainty-based IM are minimized. Here, we modulated similarity-based IM using binaural cues. Standard/deviant tones and distracting tones were presented sequentially, and level-increment thresholds were measured. Deviant tones differed from standard tones by a higher sound level. Distracting tones covered a wide range of levels. Standard/deviant tones and distracting tones were characterized by their interaural time difference (ITD), interaural level difference (ILD), or both ITD and ILD. The larger the ITD or ILD was, the better similarity-based IM was overcome. If both interaural differences were applied to standard/deviant tones, the release from IM was larger than when either interaural difference was used. The results show that binaural cues are potent cues to abolish similarity-based IM and that the auditory system makes use of multiple available cues.

Exploring binaural hearing in gerbils (Meriones unguiculatus) using virtual headphones

The Mongolian gerbil (Meriones unguiculatus) has become a key species in investigations of the neural processing of sound localization cues in mammals. While its sound localization has been tested extensively under free-field stimulation, many neurophysiological studies use headphones to present signals with binaural localization cues. The gerbils behavioral sensitivity to binaural cues, however, is unknown for the lack of appropriate stimulation paradigms in awake behaving gerbils. We close this gap in knowledge by mimicking a headphone stimulation; we use free-field loudspeakers and apply cross-talk cancellation techniques to present pure tones with binaural cues via “virtual headphones” to gerbils trained in a sound localization task. All gerbils were able to lateralize sounds depending on the interaural time or level difference (ITD and ILD, respectively). For ITD stimuli, reliable responses were seen for frequencies ≤2.9 kHz, the highest frequency tested with ITD stimuli. ITD sensitivity was frequency-dependent with the highest sensitivity observed at 1 kHz. For stimuli with ITD outside the gerbils physiological range, responses were cyclic indicating the use of phase information when lateralizing narrow-band sounds. For ILD stimuli, reliable responses were obtained for frequencies ≥2 kHz. The comparison of ITD and ILD thresholds with ITD and ILD thresholds derived from gerbils’ free-field performance suggests that ongoing ITD information is the main cue for sound localization at frequencies <2 kHz. At 2 kHz, ITD and ILD cues are likely used in a complementary way. Verification of the use of the virtual headphones suggests that they can serve as a suitable substitute for conventional headphones particularly at frequencies ≤2 kHz.

Effect of preceding stimulation on sound localization and its representation in the auditory midbrain

Prior stimulation can influence the perception of sound source location. Some psychophysical sound localization procedures differ in the amount of prior stimulation, which may affect measures of localization accuracy. If and how particularly the number of preceding stimuli affects sound localization and the neural representation of sound source position has not been investigated so far and will be the focus of the present report. We trained Mongolian gerbils in a left/right discrimination task where the target stimulus was preceded by silence or followed a number of reference stimuli. Localization thresholds decreased with the number of references presented before the target stimulus. The smallest thresholds were found after the presentation of a train of 5 reference stimuli and after silence. We recorded from units in the inferior colliculus (IC) of anaesthetized gerbils using virtual‐acoustic space stimuli mimicking the ones used in the behavioural task and applied signal detection theory to compare behavioural and neurometric thresholds. We found that neurometric thresholds based on spike rate information of single units covered a wide range of threshold values but only neurometric thresholds that were based on responses of small populations of IC units reached consistently thresholds we also observed in the behavioural experiment. Unlike behavioural thresholds, however, neurometric thresholds were independent of the number of reference stimuli suggesting that processing stages downstream from the IC might better reflect the effect of prior stimulation.

Evidence for the origin of the binaural interaction components of the auditory brainstem response

The binaural interaction component (BIC) is discussed as a potential tool to objectively measure listeners’ binaural auditory processing abilities. It is obtained from auditory brainstem responses (ABRs) by subtracting the sum of the ABRs to monaural left and monaural right stimulation from the ABR recorded under binaural stimulation. The sources of the BIC, however, have not yet been agreed upon. Candidate source regions are the lateral and medial superior olives (LSO and MSO, respectively) in the superior olivary complex where excitatory and inhibitory inputs converge. Our study aims at identifying the source of the BIC. Simultaneously to ABRs, we recorded local-field potentials (LFPs) and single-unit (SU) responses from the LSO and MSO of ketamine/xylazine-anaesthetised Mongolian gerbils and derived LFP-related and SU-related BICs the same way as ABR-related BIC. We then compared the properties of LFP-related and SU-related BICs with the ABR-related BICs. LFP-related BICs recorded in the LSO did not mi...

Release from informational masking by auditory stream segregation: perception and its neural correlate

In the analysis of acoustic scenes, we easily miss sounds or are insensitive to sound features that are salient if presented in isolation. This insensitivity that is not due to interference in the inner ear is termed informational masking (IM). So far, the cellular mechanisms underlying IM remained elusive. Here, we apply a sequential IM paradigm to humans and gerbils using a sound level increment detection task determining the sensitivity to target tones in a background of standard (same frequency) and distracting tones (varying in level and frequency). The amount of IM that was indicated by the level increment thresholds depended on the frequency separation between the distracting and the standard and target tones. In humans and gerbils, we observed similar perceptual thresholds. A release from IM of more than 20 dB was observed in both species if the distracting tones were well segregated in frequency from the other tones. Neuronal rate responses elicited by similar sequences in gerbil inferior colliculus and auditory cortex were recorded. At both levels of the auditory pathway, the neuronal thresholds obtained with a signal‐detection‐theoretic approach deducing the sensitivity from the analysis of the neurons’ receiver operating characteristics matched the psychophysical thresholds revealing that IM already emerges at midbrain level. By applying objective response measures in physiology and psychophysics, we demonstrated that the population of neurons has a sufficient sensitivity for explaining the perceptual level increment thresholds indicating IM. There was a good correspondence between the neuronal and perceptual release from IM being related to auditory stream segregation.