Publications using TDT

The neurophonic potential is a synchronized frequency-following extracellular field potential that can be recorded in the nucleus laminaris (NL) in the brainstem of the barn owl. Putative generators of the neurophonic are the afferent axons from the nucleus magnocellularis, synapses onto NL neurons, and spikes of NL neurons. The outputs of NL, i.e., action potentials of NL neurons, are only weakly represented in the neurophonic. Instead, the inputs to NL, i.e., afferent axons and their synaptic potentials, are the predominant origin of the neurophonic (Kuokkanen PT, Wagner H, Ashida G, Carr CE, Kempter R. J Neurophysiol 104: 2274–2290, 2010). Thus in NL the monaural inputs from the two brain sides converge and create a binaural neurophonic. If these monaural inputs contribute independently to the extracellular field, the response to binaural stimulation can be predicted from the sum of the responses to ipsi- and contralateral stimulation. We found that a linear summation model explains the dependence of the responses on interaural time difference as measured experimentally with binaural stimulation. The fit between model predictions and data was excellent, even without taking into account the nonlinear responses of NL coincidence detector neurons, although their firing rate and synchrony strongly depend on the interaural time difference. These results are consistent with the view that the afferent axons and their synaptic potentials in NL are the primary origin of the neurophonic.

Neuroprosthetics using intracortical microstimulation can potentially alleviate sensory deprivation due to injury or disease. However the information bandwidth of a single microstimulation channel remains largely unanswered. This paper presents three experiments that examine the importance of Peak Power/Charge and RMS Power/Charge for detection of acoustic and electrical Sinusoidal Amplitude Modulated stimuli by the auditory system. While the peripheral auditory system is sensitive to RMS power cues for the detection of acoustic stimuli, here we provide results that suggest that the auditory cortex is sensitive to peak charge cues for electrical stimuli. Varying the modulation frequency and depth do not change this effect for detection of modulated electrical stimuli.

Primary motor-cortex multi-unit activity (MUA) and local-field potentials (LFPs) have both been suggested as potential control signals for brain-computer interfaces (BCIs) aimed at movement restoration. Some studies report that LFP-based decoding is comparable to spiking-based decoding, while others offer contradicting evidence. Differences in experimental paradigms, tuning models and decoding techniques make it hard to directly compare these results. Here, we use regression and mutual information analyses to study how MUA and LFP encode various kinematic parameters during reaching movements. We find that in addition to previously reported directional tuning, MUA also contains prominent speed tuning. LFP activity in low-frequency bands (15-40Hz, LFPL) is primarily speed tuned, and contains more speed information than both high-frequency LFP (100-300Hz, LFPH) and MUA. LFPH contains more directional information compared to LFPL, but less information when compared with MUA. Our results suggest that a velocity and speed encoding model is most appropriate for both MUA and LFPH, whereas a speed only encoding model is adequate for LFPL.

Unlabelled: Opto-electronic computer holographic measurements were made of the tympanic membrane (TM) in cadaveric chinchillas. Measurements with two laser wavelengths were used to compute the 3D-shape of the TM. Single laser wavelength measurements locked to eight distinct phases of a tonal stimulus were used to determine the magnitude and the relative phase of the surface displacements. These measurements were made at over 250,000 points on the TM surface. The measured motions contained spatial phase variations consistent with relatively low-order (large spatial frequency) modal motions and smaller magnitude higher-order (smaller spatial frequency) motions that appear to travel, but may also be explained by losses within the membrane. The measurement of shape and thin shell theory allowed us to separate the measured motions into those components orthogonal to the plane of the tympanic ring, and those components within the plane of the tympanic ring based on the 3D-shape. The predicted in-plane motion components are generally smaller than the out-of-plane perpendicular component of motion. Since the derivation of in-plane and out-of plane depended primarily on the membrane shape, the relative sizes of the predicted motion components did not vary with frequency. Summary: A new method for simultaneously measuring the shape and sound-induced motion of the tympanic membrane is utilized to estimate the 3D motion on the membrane surface. This article is part of a special issue entitled "MEMRO 2012".

The use of genetically modified mice can accelerate progress in auditory research. However, the fundamental profile of mouse hearing has not been thoroughly documented. In the current study, we explored mouse middle ear transmission by measuring sound-evoked vibrations at several key points along the ossicular chain using a laser-Doppler vibrometer. Observations were made through an opening in pars flaccida. Simultaneously, the pressure at the tympanic membrane close to the umbo was monitored using a micro-pressure-sensor. Measurements were performed in C57BL mice, which are widely used in hearing research. Our results show that the ossicular local transfer function, defined as the ratio of velocity to the pressure at the tympanic membrane, was like a high-pass filter, almost flat at frequencies above ∼15 kHz, decreasing rapidly at lower frequencies. There was little phase accumulation along the ossicles. Our results suggested that the mouse ossicles moved almost as a rigid body. Based on these 1-dimensional measurements, the malleus-incus-complex primarily rotated around the anatomical axis passing through the gonial termination of the anterior malleus and the short process of the incus, but secondary motions were also present. This article is part of a special issue entitled "MEMRO 2012".

Cardiac Arrest (CA) leads to a global hypoxic-ischemic injury in the brain leading to a poor neurological outcome. Understanding the mechanisms of functional disruption in various regions of the brain may be essential for the development of improved diagnostic and therapeutic solutions. Using controlled laboratory experiment with animal models of CA, our primary focus here is on understanding the functional changes in the thalamus and the cortex, associated with the injury and acute recovery upon resuscitation. Specifically, to study the changes in thalamocortical synchrony through these periods, we acquired local field potentials (LFPs) from the ventroposterior lateral (VPL) nucleus of the thalamus and the forelimb somatosensory cortex (S1FL) in rats after asphyxial CA. Band-specific relative Hilbert phases were used to analyze synchrony between the LFPs. We observed that the CA induced global ischemia changes the local phase-relationships by introducing a phase-lag in both the thalamus and the cortex, while the synchrony between the two regions is nearly completely lost after CA.

Inputs from the two eyes are first combined in simple cells in the primary visual cortex. Consequently, visual cortical neurons need to have the flexibility to encode visual features under both monocular and binocular situations. Here we show that binocular orientation selectivity of mouse simple cells is nearly identical to monocular orientation selectivity in both anaesthetized and awake conditions. In vivo whole-cell recordings reveal that the binocular integration of membrane potential responses is sublinear. The sublinear integration keeps binocularly evoked depolarizations below threshold at non-preferred orientations, thus preserving orientation selectivity. Computational simulations based on measured synaptic conductances indicate that inhibition promotes sublinear binocular integration, which are further confirmed by experiments using genetic and pharmacological manipulations. Our findings therefore reveal a cellular mechanism for how visual system can switch effortlessly between monocular and binocular conditions. The same mechanism may apply to other sensory systems that also integrate multiple channels of inputs.

In all sensory modalities, intracortical inhibition shapes the functional properties of cortical neurons but also influences the responses to natural stimuli. Studies performed in various species have revealed that auditory cortex neurons respond to conspecific vocalizations by temporal spike patterns displaying a high trial-to-trial reliability, which might result from precise timing between excitation and inhibition. Studying the guinea pig auditory cortex, we show that partial blockage of GABAA receptors by gabazine (GBZ) application (10 μm, a concentration that promotes expansion of cortical receptive fields) increased the evoked firing rate and the spike-timing reliability during presentation of communication sounds (conspecific and heterospecific vocalizations), whereas GABAB receptor antagonists [10 μm saclofen; 10-50 μm CGP55845 (p-3-aminopropyl-p-diethoxymethyl phosphoric acid)] had nonsignificant effects. Computing mutual information (MI) from the responses to vocalizations using either the evoked firing rate or the temporal spike patterns revealed that GBZ application increased the MI derived from the activity of single cortical site but did not change the MI derived from population activity. In addition, quantification of information redundancy showed that GBZ significantly increased redundancy at the population level. This result suggests that a potential role of intracortical inhibition is to reduce information redundancy during the processing of natural stimuli.

Over 120 loci are known to cause inherited hearing loss in humans. The deafness gene has been identified for only half of these loci. With the aim of identifying some of the remaining deafness genes, we performed an ethylnitrosourea mutagenesis screen for deaf mice. We isolated two mutants with semi-dominant hearing loss, Deaf11 and Deaf13. Both contained causative mutations in Atp2b2, which encodes the plasma membrane calcium ATPase 2. The Atp2b2 (Deaf11) mutation leads to a p. I1023S substitution in the tenth transmembrane domain. The Atp2b2 (Deaf13) mutation leads to a p. R561S substitution in the catalytic core. Mice homozygous for these mutations display profound hearing loss. Heterozygotes display mild to moderate, progressive hearing loss.

In recordings from anterior piriform cortex in awake behaving mice, we found that neuronal firing early in the olfactory pathway simultaneously conveyed fundamentally different information: odor value (is the odor rewarded?) and identity (what is the smell?). Thus, this sensory system performs early multiplexing of information reflecting stimulus-specific characteristics with that used for decision-making.

Estimating the fitness surface of rapidly evolving secondary sexual traits can elucidate the origins of sexual isolation and thus speciation. Evidence suggests that sexual selection is highly complex in nature, often acting on multivariate sexual characters that sometimes include non-heritable components of variation, thus presenting a challenge for predicting patterns of sexual trait evolution. Laupala crickets have undergone an explosive species radiation marked by divergence in male courtship song and associated female preferences, yet patterns of sexual selection that might explain this diversification remain unknown. We used female phonotaxis trials to estimate the fitness surface for acoustic characters within one population of Laupala cerasina , a species with marked geographical variation in male song and female preferences. Results suggested significant directional sexual selection on three major song traits, while canonical rotation of the matrix of nonlinear selection coefficients ( γ ) revealed the presence of significant convex (stabilizing) sexual selection along combinations of characters. Analysis of song variation within and among males indicated significantly higher repeatability along the canonical axis of greatest stabilizing selection than along the axis of greatest linear selection. These results are largely consistent with patterns of song divergence that characterize speciation and suggest that different song characters have the potential to indicate distinct information to females during courtship.

Cochlear implants restore hearing cues in the severe–profoundly deaf by electrically stimulating spiral ganglion neurons (SGNs). However, SGNs degenerate following loss of cochlear hair cells, due at least in part to a reduction in the endogenous neurotrophin (NT) supply, normally provided by hair cells and supporting cells of the organ of Corti. Delivering exogenous NTs to the cochlea can rescue SGNs from degeneration and can also promote the ectopic growth of SGN neurites. This resprouting may disrupt the cochleotopic organization upon which cochlear implants rely to impart pitch cues. Using retrograde labeling and confocal imaging of SGNs, we determined the extent of neurite growth following 28 days of exogenous NT treatment in deafened guinea pigs with and without chronic electrical stimulation (ES). On completion of this treatment, we measured the spread of neural activation to intracochlear ES by recording neural responses across the cochleotopically organized inferior colliculus using multichannel recording techniques. Although NT treatment significantly increased both the length and the lateral extent of growth of neurites along the cochlea compared with deafened controls, these anatomical changes did not affect the spread of neural activation when examined immediately after 28 days of NT treatment. NT treatment did, however, result in lower excitation thresholds compared with deafened controls. These data support the application of NTs for improved clinical outcomes for cochlear implant patients. J. Comp. Neurol. 521:2818–2832, 2013. © 2013 Wiley Periodicals, Inc.

Many natural sounds are periodic and consist of frequencies (harmonics) that are integer multiples of a common fundamental frequency (F0). Such harmonic complex tones (HCTs) evoke a pitch corresponding to their F0, which plays a key role in the perception of speech and music. "Pitch-selective" neurons have been identified in non-primary auditory cortex of marmoset monkeys. Noninvasive studies point to a putative "pitch center" located in a homologous cortical region in humans. It remains unclear whether there is sufficient spectral and temporal information available at the level of primary auditory cortex (A1) to enable reliable pitch extraction in non-primary auditory cortex. Here we evaluated multiunit responses to HCTs in A1 of awake macaques using a stimulus design employed in auditory nerve studies of pitch encoding. The F0 of the HCTs was varied in small increments, such that harmonics of the HCTs fell either on the peak or on the sides of the neuronal pure tone tuning functions. Resultant response-amplitude-versus-harmonic-number functions ("rate-place profiles") displayed a periodic pattern reflecting the neuronal representation of individual HCT harmonics. Consistent with psychoacoustic findings in humans, lower harmonics were better resolved in rate-place profiles than higher harmonics. Lower F0s were also temporally represented by neuronal phase-locking to the periodic waveform of the HCTs. Findings indicate that population responses in A1 contain sufficient spectral and temporal information for extracting the pitch of HCTs by neurons in downstream cortical areas that receive their input from A1.

The involvement of retrosplenial cortex (RSC) in human autobiographical memory retrieval has been confirmed by functional brain imaging studies, and is supported by anatomical evidence of strong connectivity between the RSC and memory structures within the medial temporal lobe (MTL). However, electrophysiological investigations of the RSC and its interaction with the MTL have mostly remained limited to the rodent brain. Recently, we reported a selective increase of high-frequency broadband (HFB; 70-180 Hz) power within the human RSC during autobiographical retrieval, and a predominance of 3-5 Hz theta band oscillations within the RSC during the resting state. In the current study, we aimed to explore the temporal dynamics of theta band interaction between human RSC and MTL during autobiographical retrieval. Toward this aim, we obtained simultaneous recordings from the RSC and MTL in human subjects undergoing invasive electrophysiological monitoring, and quantified the strength of RSC-MTL theta band phase locking. We observed significant phase locking in the 3-4 Hz theta range between the RSC and the MTL during autobiographical retrieval. This theta band phase coupling was transient and peaked at a consistent latency before the peak of RSC HFB power across subjects. Control analyses confirmed that theta phase coupling between the RSC and MTL was not seen for other conditions studied, other sites of recording, or other frequency ranges of interest (1-20 Hz). Our findings provide the first evidence of theta band interaction between the human RSC and MTL during conditions of autobiographical retrieval.

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. Although features of the FFR have been widely used as indices of pitch coding acuity, only a handful of studies have directly investigated the relation between the FFR and behavioral pitch judgments. Furthermore, the contribution of degraded neural synchrony (as indexed by the FFR) to the pitch perception impairments of older listeners and those with hearing loss is not well known. Here, the relation between the FFR and pure-tone frequency discrimination was investigated in listeners with a wide range of ages and absolute thresholds, to assess the respective contributions of subcortical neural synchrony and other age-related and hearing loss-related mechanisms to frequency discrimination performance. FFR measures of neural synchrony and absolute thresholds independently contributed to frequency discrimination performance. Age alone, i.e., once the effect of subcortical neural synchrony measures or absolute thresholds had been partialed out, did not contribute to frequency discrimination. Overall, the results suggest that frequency discrimination of pure tones may depend both on phase locking precision and on separate mechanisms affected in hearing loss.

Damage to the medial temporal lobe impairs the encoding of new memories and the retrieval of memories acquired immediately before the damage in human. In this study, we demonstrated that artificial visuoauditory memory traces can be established in the rat auditory cortex and that their encoding and retrieval depend on the entorhinal cortex of the medial temporal lobe in the rat. We trained rats to associate a visual stimulus with electrical stimulation of the auditory cortex using a classical conditioning protocol. After conditioning, we examined the associative memory traces electrophysiologically (i.e., visual stimulus-evoked responses of auditory cortical neurons) and behaviorally (i.e., visual stimulus-induced freezing and visual stimulus-guided reward retrieval). The establishment of a visuoauditory memory trace in the auditory cortex, which was detectable by electrophysiological recordings, was achieved over 20-30 conditioning trials and was blocked by unilateral, temporary inactivation of the entorhinal cortex. Retrieval of a previously established visuoauditory memory was also affected by unilateral entorhinal cortex inactivation. These findings suggest that the entorhinal cortex is necessary for the encoding and involved in the retrieval of artificial visuoauditory memory in the auditory cortex, at least during the early stages of memory consolidation.

Atonal homolog1 (Atoh1) encodes a basic helix-loop-helix protein that is the first transcription factor to be expressed in differentiating hair cells. Previous work suggests that expression of Atoh1 in prosensory precursors is necessary for the differentiation and survival of hair cells, but it is not clear whether Atoh1 is required exclusively for these processes, or whether it regulates other functions later during hair cell maturation. We used EGFP-tagged Atoh1 knock-in mice to demonstrate for the first time that Atoh1 protein is expressed in hair cell precursors several days before the appearance of differentiated markers, but not in the broad pattern expected of a proneural gene. We conditionally deleted Atoh1 at different points in hair cell development and observe a rapid onset of hair cell defects, suggesting that the Atoh1 protein is unstable in differentiating hair cells and is necessary through an extended phase of their differentiation. Conditional deletion of Atoh1 reveals multiple functions in hair cell survival, maturation of stereociliary bundles, and auditory function. We show the presence of distinct critical periods for Atoh1 in each of these functions, suggesting that Atoh1 may be directly regulating many aspects of hair cell function. Finally, we show that the supporting cell death that accompanies loss of Atoh1 in hair cells is likely caused by the abortive trans-differentiation of supporting cells into hair cells. Together our data suggest that Atoh1 regulates multiple aspects of hair cell development and function.

This study tested the hypothesis that the reduced spatial release from speech-on-speech masking typically observed in listeners with sensorineural hearing loss results from increased energetic masking. Target sentences were presented simultaneously with a speech masker, and the spectral overlap between the pair (and hence the energetic masking) was systematically varied. The results are consistent with increased energetic masking in listeners with hearing loss that limits performance when listening in speech mixtures. However, listeners with hearing loss did not exhibit reduced spatial release from masking when stimuli were filtered into narrow bands.

Neurons in the medial superior olive (MSO) enable sound localization by their remarkable sensitivity to submillisecond interaural time differences (ITDs). Each MSO neuron has its own "best ITD" to which it responds optimally. A difference in physical path length of the excitatory inputs from both ears cannot fully account for the ITD tuning of MSO neurons. As a result, it is still debated how these inputs interact and whether the segregation of inputs to opposite dendrites, well-timed synaptic inhibition, or asymmetries in synaptic potentials or cellular morphology further optimize coincidence detection or ITD tuning. Using in vivo whole-cell and juxtacellular recordings, we show here that ITD tuning of MSO neurons is determined by the timing of their excitatory inputs. The inputs from both ears sum linearly, whereas spike probability depends nonlinearly on the size of synaptic inputs. This simple coincidence detection scheme thus makes accurate sound localization possible.

Although numerous causative genes for hereditary hearing loss have been identified, there are no fundamental treatments for this condition. Herein, we describe a novel potential treatment for genetic hearing loss. Because mutations or deletions in the connexin (Cx) genes are common causes of profound congenital hearing loss in both humans and mice, we investigated whether gene supplementation therapy using the wild-type Cx gene could cure hearing loss. We first generated inner ear-specific connexin 30 (Cx30)-deficient mice via the transuterine transfer of Cx30-targeted short hairpin RNA (shRNA-Cx30) into otocysts. The inner ear-specific Cx30-deficient mice mimicked homozygous Cx30-deficient mice both histologically and physiologically. Subsequently, we cotransfected the shRNA-Cx30 and the wild-type Cx30 gene. The cotransfected mice exhibited Cx30 expression in the cochleae and displayed normal auditory functions. Next, we performed the transuterine transfer of the wild-type Cx30 gene into the otocysts of homozygous Cx30-deficient mice, thereby rescuing the lack of Cx30 expression in the cochleae and restoring auditory functioning. These results demonstrate that supplementation therapy with wild-type genes can restore postnatal auditory functioning. Moreover, this is the first report to show that Cx-related genetic hearing loss is treatable by in vivo gene therapy.