Spectral Composition of Concurrent Noise Affects Neuronal Sensitivity to Interaural Time Differences of Tones in the Dorsal Nucleus of the Lateral Lemniscus

2007 ◽  
Vol 98 (5) ◽  
pp. 2705-2715 ◽  
Author(s):  
Ida Siveke ◽  
Christian Leibold ◽  
Benedikt Grothe
Keyword(s):  
White Noise ◽  
Response Rate ◽  
Spectral Composition ◽  
Low Frequency ◽  
Maximal Response ◽  
Lateral Lemniscus ◽  
Interaural Time Differences ◽  
Binaural Cues ◽  
Dorsal Nucleus ◽  
Monaural Stimulation

We are regularly exposed to several concurrent sounds, producing a mixture of binaural cues. The neuronal mechanisms underlying the localization of concurrent sounds are not well understood. The major binaural cues for localizing low-frequency sounds in the horizontal plane are interaural time differences (ITDs). Auditory brain stem neurons encode ITDs by firing maximally in response to “favorable” ITDs and weakly or not at all in response to “unfavorable” ITDs. We recorded from ITD-sensitive neurons in the dorsal nucleus of the lateral lemniscus (DNLL) while presenting pure tones at different ITDs embedded in noise. We found that increasing levels of concurrent white noise suppressed the maximal response rate to tones with favorable ITDs and slightly enhanced the response rate to tones with unfavorable ITDs. Nevertheless, most of the neurons maintained ITD sensitivity to tones even for noise intensities equal to that of the tone. Using concurrent noise with a spectral composition in which the neuron's excitatory frequencies are omitted reduced the maximal response similar to that obtained with concurrent white noise. This finding indicates that the decrease of the maximal rate is mediated by suppressive cross-frequency interactions, which we also observed during monaural stimulation with additional white noise. In contrast, the enhancement of the firing rate to tones at unfavorable ITD might be due to early binaural interactions (e.g., at the level of the superior olive). A simple simulation corroborates this interpretation. Taken together, these findings suggest that the spectral composition of a concurrent sound strongly influences the spatial processing of ITD-sensitive DNLL neurons.

The roles of GABAergic and glycinergic inhibition on binaural processing in the dorsal nucleus of the lateral lemniscus of the mustache bat

1994 ◽  
Vol 71 (6) ◽  
pp. 1999-2013 ◽  
Author(s):  
L. Yang ◽  
G. D. Pollak
Keyword(s):  
Tone Burst ◽  
Gabaergic Inhibition ◽  
Gamma Aminobutyric Acid ◽  
Lateral Lemniscus ◽  
Dorsal Nucleus ◽  
Iontophoretic Application ◽  
Monaural Stimulation ◽  
Contralateral Ear ◽  
Glycinergic Inhibition ◽  
Stimulation Of

1. We studied the monaural and binaural response properties of 99 neurons in the dorsal nucleus of the lateral lemniscus (DNLL) of the mustache bat before and during the iontophoretic application of antagonists that blocked gamma-aminobutyric acid-A (GABAA) receptors (bicuculline) or glycine receptors (strychnine). All cells were driven by monaural stimulation of the contralateral ear, whereas monaural stimulation of the ipsilateral ear never evoked discharges. The binaural properties of 81 neurons were determined by holding the intensity constant at the contralateral ear and presenting a variety of intensities to the ipsilateral ear. This procedure generated interaural intensity disparity (IID) functions and allowed us to determine the effect of ipsilaterally evoked inhibition on a constant excitatory drive evoked by the contralateral ear. 2. One of the main findings is that the IID functions in the majority of DNLL neurons were not affected by application of either strychnine or bicuculline. Blocking glycinergic inhibition with strychnine had no effect on the IID functions in 75% of the cells studied. However, strychnine did change the IID functions in approximately 25% of the DNLL population. In those cells glycinergic inhibition appeared to be partially, or, in a few cases, entirely responsible for the ipsilaterally evoked spike suppression. In contrast, blocking GABAergic inhibition with bicuculline had no discernible effect on the ipsilaterally evoked spike suppression in any of the excitatory/inhibitory cells that we recorded. GABAergic inhibition, therefore, plays no role in the formation of IID functions of neurons in the DNLL. Furthermore, the results suggest that glycinergic inhibition also does not contribute to the suppression of spikes evoked by stimulation of the contralateral ear in the vast majority of DNLL neurons. 3. Although the majority of IID functions were not influenced when either GABAergic or glycinergic innervation was blocked, ipsilateral stimulation alone evoked both a glycinergic and GABAergic inhibition in most DNLL cells. These inhibitory events were demonstrated in 18 other cells by evoking discharges with the iontophoretic application of glutamate. Stimulating the ipsilateral ear alone under these conditions caused a suppression of the glutamate-evoked discharges. Furthermore, the spike suppression persisted for a period of time that was longer than the duration of the tone burst at the ipsilateral ear. 4. The application of bicuculline or strychnine had different effects on the glutamate-elicited spikes. Bicuculline reduced the duration of the inhibition, and it was always the latter portion of the inhibition that was abolished by bicuculline. In more than half of the cells studied strychnine also reduced the duration of the inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)

Binaural Response Properties of Low-Frequency Neurons in the Gerbil Dorsal Nucleus of the Lateral Lemniscus

2006 ◽  
Vol 96 (3) ◽  
pp. 1425-1440 ◽  
Author(s):  
Ida Siveke ◽  
Michael Pecka ◽  
Armin H. Seidl ◽  
Sylvie Baudoux ◽  
Benedikt Grothe
Keyword(s):  
Low Frequency ◽  
Superior Olivary Complex ◽  
Suitable Model ◽  
Medial Superior Olive ◽  
Lateral Lemniscus ◽  
Auditory Midbrain ◽  
Response Properties ◽  
Superior Olive ◽  
Dorsal Nucleus ◽  
Anatomical Evidence

Differences in intensity and arrival time of sounds at the two ears, interaural intensity and time differences (IID, ITD), are the chief cues for sound localization. Both cues are initially processed in the superior olivary complex (SOC), which projects to the dorsal nucleus of the lateral lemniscus (DNLL) and the auditory midbrain. Here we present basic response properties of low-frequency (<2 kHz) DNLL neurons and their binaural sensitivity to ITDs and IIDs in the anesthetized gerbil. We found many neurons showing binaural properties similar to those reported for SOC neurons. IID-properties were similar to that of the contralateral lateral superior olive (LSO). A majority of cells had an ITD sensitivity resembling that of either the ipsilateral medial superior olive (MSO) or the contralateral LSO. A smaller number of cells displayed intermediate types of ITD sensitivity. In neurons with MSO-like response ITDs that evoked maximal discharges were mostly outside of the range of ITDs the gerbil naturally experiences. The maxima of the first derivative of their ITD-functions (steepest slope), however, were well within the physiological range of ITDs. This finding is consistent with the concept of a population rather than a place code for ITDs. Moreover, we describe several other binaural properties as well as physiological and anatomical evidence for a small but significant input from the contralateral MSO. The large number of ITD-sensitive low-frequency neurons implicates a substantial role for the DNLL in ITD processing and promotes this nucleus as a suitable model for further studies on ITD-coding.

Sensitivity to Interaural Time Differences in the Dorsal Nucleus of the Lateral Lemniscus of the Unanesthetized Rabbit: Comparison With Other Structures

2006 ◽  
Vol 95 (3) ◽  
pp. 1309-1322 ◽  
Author(s):  
Shigeyuki Kuwada ◽  
Douglas C. Fitzpatrick ◽  
Ranjan Batra ◽  
Ernst-Michael Ostapoff
Keyword(s):  
Inferior Colliculus ◽  
Phase Locking ◽  
Large Majority ◽  
Superior Olivary Complex ◽  
Inhibitory Input ◽  
Lateral Lemniscus ◽  
Interaural Time Differences ◽  
Auditory Thalamus ◽  
Dorsal Nucleus ◽  
Unanesthetized Rabbit

Interaural time differences, a cue for azimuthal sound location, are first encoded in the superior olivary complex (SOC), and this information is then conveyed to the dorsal nucleus of the lateral lemniscus (DNLL) and inferior colliculus (IC). The DNLL provides a strong inhibitory input to the IC and may serve to transform the coding of interaural time differences (ITDs) in the IC. Consistent with the projections from the SOC, the DNLL and IC had similar distributions of peak- and trough-type neurons, characteristic delays, and best ITDs. The ITD tuning widths of DNLL neurons were intermediate between those of the SOC and IC. Further sharpening is seen in the auditory thalamus, indicating that sharpening mechanisms are not restricted to the midbrain. The proportion of neurons that phase-locked to the tones delivered to each ear progressively decreased from the SOC to the auditory thalamus. The degree of phase-locking for a large majority of DNLL neurons was too weak to support their involvement in processing monaural inputs to generate a sensitivity to ITDs. The response rates of DNLL neurons were on average ∼60% greater than in the IC or SOC, indicating that the inhibitory input provided to the IC by the DNLL is robust.

scholarly journals Coexistence of perseveration and apathy in the TDP-43Q331K knock-in mouse model of ALS–FTD

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Eosu Kim ◽  
Matthew A. White ◽  
Benjamin U. Phillips ◽  
Laura Lopez-Cruz ◽  
Hyunjeong Kim ◽  
...  
Keyword(s):  
Translational Research ◽  
Cognitive Flexibility ◽  
Visual Discrimination ◽  
Response Rate ◽  
Psychological Symptoms ◽  
Progressive Ratio ◽  
Maximal Response ◽  
Behavioural Phenotype ◽  
Rate Analysis ◽  
Lateral Sclerosis

Abstract Perseveration and apathy are two of the most common behavioural and psychological symptoms of dementia (BPSDs) in amyotrophic lateral sclerosis–frontotemporal dementia (ALS–FTD). Availability of a validated and behaviourally characterised animal model is crucial for translational research into BPSD in the FTD context. We behaviourally evaluated the male TDP-43Q331K mouse, an ALS–FTD model with a human-equivalent mutation (TDP-43Q331K) knocked into the endogenous Tardbp gene. We utilised a panel of behavioural tasks delivered using the rodent touchscreen apparatus, including progressive ratio (PR), extinction and visual discrimination/reversal learning (VDR) assays to examine motivation, response inhibition and cognitive flexibility, respectively. Relative to WT littermates, TDP-43Q331K mice exhibited increased responding under a PR schedule. While elevated PR responding is typically an indication of increased motivation for reward, a trial-by-trial response rate analysis revealed that TDP-43Q331K mice exhibited decreased maximal response rate and slower response decay rate, suggestive of reduced motivation and a perseverative behavioural phenotype, respectively. In the extinction assay, TDP-43Q331K mice displayed increased omissions during the early phase of each session, consistent with a deficit in activational motivation. Finally, the VDR task revealed cognitive inflexibility, manifesting as stimulus-bound perseveration. Together, our data indicate that male TDP-43Q331K mice exhibit a perseverative phenotype with some evidence of apathy-like behaviour, similar to BPSDs observed in human ALS–FTD patients. The TDP-43Q331K knock-in mouse therefore has features that recommend it as a useful platform to facilitate translational research into behavioural symptoms in the context of ALS–FTD.

Institutional experience with nab-sirolimus in patients with malignancies harboring TSC1 or TSC2 mutations.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3111-3111
Author(s):  
Mark Andrew Dickson ◽  
Vinod Ravi ◽  
Kristen N. Ganjoo ◽  
Gopa Iyer
Keyword(s):  
Response Rate ◽  
Xenograft Model ◽  
Low Frequency ◽  
Mtor Pathway ◽  
Serious Adverse Events ◽  
Improved Outcomes ◽  
S 100 ◽  
Institutional Experience ◽  
Tumor Accumulation ◽  
Tumor Types

3111 Background: TSC1/ TSC2 genes are tumor suppressors in the mTOR pathway; mutated at low frequency across tumor types (̃1–2%). Retrospective analyses of patients (pts) with mTOR pathway mutations treated with everolimus did not show improved outcomes vs the wild type (Voss et al. Clin Cancer Res 2019. PMID 30327302). In NCT02201212, pts with TSC1/TSC2 mutations treated with everolimus had a 7% (2/30) response rate. In the AMPECT study, pts with advanced PEComa treated with a novel mTOR inhibitor (mTORi), nab-sirolimus ( nab-S, ABI-009), the subset of pts with TSC1/TSC2 mutations had a response rate of 64% (9/14) (Wagner et al. CTOS 2020. #3463014). In a xenograft model, nab-S showed significantly higher tumor accumulation, target suppression (pS6) and antitumor activity vs everolimus or sirolimus (Hou et al. AACR 2019. #348). In an expanded access program (NCT03817515), pts with advanced tumors bearing TSC1/ TSC2 mutations were treated with nab-S and outcomes in pts with malignancies other than PEComa are reported herein. Methods: Eligible pts (ECOG 0–2) received nab-S 100 mg/m2 IV, once weekly for 2 of every 3 weeks at 3 US sites between 7/2019 and 11/2020. Results: 7 pts with TSC1/ TSC2 mutations have been consecutively enrolled and are reported here. 6/7 pts had multiple prior therapies including 2 pts previously progressing on an mTORi. 4/7 pts had partial response (PR), all in mTORi naïve pts. 2/7 pts had stable disease (SD). In 2 pts previously treated with an mTORi, 1 had SD and 1 came off treatment after 1 cycle (CA125 ↑) with no follow-up scan. Treatment-related serious adverse events (SAEs; hyperglycemia and infection) and dose reduction were reported in 1 pt with metastatic angiosarcoma; SAEs resolved and the pt continued Rx. No other SAE or dose limiting event was reported Conclusions: Patients with various malignancies bearing TSC1 or TSC2 mutations, most with progression on multiple prior therapies, showed evidence of response and manageable toxicities during treatment with nab-S. A basket trial of nab-S in malignancies with TSC1/ TSC2 mutations is planned. Clinical trial information: NCT03817515. [Table: see text]

COMPARATIVE ANALYSIS OF SPECTRA OF THE 2000-YEAR NORTHERN HEMISPHERE AVERAGE SURFACE AIR TEMPERATURE RECONSTRUCTIONS

2021 ◽  
pp. 5-13
Author(s):  
N. M. DATSENKO ◽  
◽  
D. M. SONECHKIN ◽  
B. YANG ◽  
J.-J. LIU ◽  
...  
Keyword(s):  
High Resolution ◽  
Northern Hemisphere ◽  
Air Temperature ◽  
Wavelet Transforms ◽  
Spectral Composition ◽  
Low Frequency ◽  
Surface Air Temperature ◽  
Temporal Variations ◽  
Continuous Wavelet Transforms ◽  
Stable Estimation

The spectral composition of temporal variations in the Northern Hemisphere mean surface air temperature is estimated and compared in 2000-year paleoclimatic reconstructions. Continuous wavelet transforms of these reconstructions are used for the stable estimation of energy spectra. It is found that low-frequency parts of the spectra (the periods of temperature variations of more than 100 years) based on such high-resolution paleoclimatic indicators as tree rings, corals, etc., are similar to the spectrum of white noise, that is never observed in nature. This seems unrealistic. The famous reconstruction called “Hockey Stick” is among such unrealistic reconstructions. Reconstructions based not only on high-resolution but also on low-resolution indicators seem to be more realistic, since the low-frequency parts of their spectra have the pattern of red noise. They include the “Boomerang” reconstruction showing that some warm periods close to the present-day one were observed in the past.

Hyperpolarization-Activated Inward Current in Neurons of the Rat's Dorsal Nucleus of the Lateral Lemniscus In Vitro

1997 ◽  
Vol 78 (5) ◽  
pp. 2235-2245 ◽  
Author(s):  
Xiao Wen Fu ◽  
Borys L. Brezden ◽  
Shu Hui Wu
Keyword(s):  
Membrane Potential ◽  
Input Resistance ◽  
Resting Potential ◽  
Extracellular Potassium ◽  
Current Clamp ◽  
Lateral Lemniscus ◽  
Inward Current ◽  
Dorsal Nucleus ◽  
Maximal Activation

Fu, Xiao Wen, Borys L. Brezden, and Shu Hui Wu. Hyperpolarization-activated inward current in neurons of the rat's dorsal nucleus of the lateral lemniscus in vitro. J. Neurophysiol. 78: 2235–2245, 1997. The hyperpolarization-activated current ( I h) underlying inward rectification in neurons of the rat's dorsal nucleus of the lateral lemniscus (DNLL) was investigated using whole cell patch-clamp techniques. Patch recordings were made from DNLL neurons of young rats (21–30 days old) in 400 μm tissue slices. Under current clamp, injection of negative current produced a graded hyperpolarization of the cell membrane, often with a gradual sag in the membrane potential toward the resting value. The rate and magnitude of the sag depended on the amount of hyperpolarizing current. Larger current resulted in a larger and faster decay of the voltage. Under voltage clamp, hyperpolarizing voltage steps elicited a slowly activating inward current that was presumably responsible for the sag observed in the voltage response to a steady hyperpolarizing current recorded under current clamp. Activation of the inward current ( I h) was voltage and time dependent. The current just was seen at a membrane potential of −70 mV and was activated fully at −140 mV. The voltage value of half-maximal activation of I h was −78.0 ± 6.0 (SE) mV. The rate of I h activation was best approximated by a single exponential function with a time constant that was voltage dependent, ranging from 276 ± 27 ms at −100 mV to 186 ± 11 ms at −140 mV. Reversal potential ( E h) of I h current was more positive than the resting potential. Raising the extracellular potassium concentration shifted E h to a more depolarized value, whereas lowering the extracellular sodium concentration shifted E h in a more negative direction. I h was sensitive to extracellular cesium but relatively insensitive to extracellular barium. The current amplitude near maximal-activation (about −140 mV) was reduced to 40% of control by 1 mM cesium but was reduced to only 71% of control by 2 mM barium. When the membrane potential was near the resting potential (about −60 mV), cesium had no effect on the membrane potential, current-evoked firing rate and input resistance but reduced the spontaneous firing. When the membrane potential was more negative than −70 mV, cesium hyperpolarized the cell, decreased current-evoked firing and increased the input resistance. I h in DNLL neurons does not contribute to the normal resting potential but may enhance the extent of excitation, thereby making the DNLL a consistently powerful inhibitory source to upper levels of the auditory system.

scholarly journals Inhibition in the balance: binaurally coupled inhibitory feedback in sound localization circuitry

2011 ◽  
Vol 106 (1) ◽  
pp. 4-14 ◽  
Author(s):  
R. Michael Burger ◽  
Iwao Fukui ◽  
Harunori Ohmori ◽  
Edwin W. Rubel
Keyword(s):  
Sound Localization ◽  
Arrival Time ◽  
Dynamic Range ◽  
Low Frequency ◽  
Neural Circuitry ◽  
Significant Progress ◽  
Interaural Time Differences ◽  
Inhibitory Function ◽  
Inhibitory Feedback ◽  
Auditory Systems

Interaural time differences (ITDs) are the primary cue animals, including humans, use to localize low-frequency sounds. In vertebrate auditory systems, dedicated ITD processing neural circuitry performs an exacting task, the discrimination of microsecond differences in stimulus arrival time at the two ears by coincidence-detecting neurons. These neurons modulate responses over their entire dynamic range to sounds differing in ITD by mere hundreds of microseconds. The well-understood function of this circuitry in birds has provided a fruitful system to investigate how inhibition contributes to neural computation at the synaptic, cellular, and systems level. Our recent studies in the chicken have made significant progress in bringing together many of these findings to provide a cohesive picture of inhibitory function.

scholarly journals Spectral Characteristics of Acoustic Emission in Carbon Fiber-Reinforced Composite Materials Subjected to Cyclic Loading

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Vladimir L. Shkuratnik ◽  
Petr V. Nikolenko
Keyword(s):  
Acoustic Emission ◽  
Composite Materials ◽  
Carbon Fiber ◽  
Spectral Characteristics ◽  
Spectral Composition ◽  
Low Frequency ◽  
Sharp Change ◽  
Kaiser Effect ◽  
Emission Activity ◽  
The Time Domain

The article is devoted to the investigation of the spectral characteristics of acoustic emission signals that appear under various schemes of composite materials loading. The tests involved samples of composites reinforced with layers sheets of carbon fiber fabric and dispersed carbon fibers. Based on the results of laboratory tests, a comparison is made between the traditional parameters of acoustic emission and the complete spectrograms of the acoustic emission response developed with the use of a special algorithm. The relationship between the emission activity and the change in the spectral composition of emission hits is shown. For example, for some composites, the acoustic emission memory effect (Kaiser effect) manifests itself not only in the time domain but also in the spectral domain in a form of a sharp change in the amplitudes in the frequency range 130/150 kHz. Also, when the samples were loaded according to the Brazilian scheme, the presence of the so-called “inverse” Kaiser effect is observed, in which the memory carrier “remembers” the previously experienced level of tensile stresses and reproduces this information during subsequent unloading. Such effect manifests itself in the form of a sharp change in the amplitudes in the low-frequency region of the spectrum.

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