scholarly journals Soma-axon coupling configurations that enhance neuronal coincidence detection

2018 ◽  
Author(s):  
Joshua H Goldwyn ◽  
Michiel WH Remme ◽  
John Rinzel
Keyword(s):  
Parameter Space ◽  
Negative Feedback ◽  
Potassium Current ◽  
Auditory Brainstem ◽  
Coincidence Detection ◽  
Detection Sensitivity ◽  
Medial Superior Olive ◽  
Coupled Models ◽  
Input Region ◽  
Low Threshold

AbstractCoincidence detector neurons transmit timing information by responding preferentially to concurrent synaptic inputs. Principal cells of the medial superior olive (MSO) in the mammalian auditory brainstem are superb coincidence detectors. They encode sound source location with high temporal precision, distinguishing submillisecond timing differences among inputs. We investigate computationally how dynamic coupling between the “input” region (soma and dendrite) and the spike-generating “output” region (axon and axon initial segment) can enhance coincidence detection in MSO neurons. To do this, we formulate a two-compartment neuron model and characterize extensively coincidence detection sensitivity throughout a parameter space of coupling configurations. We focus on the interaction between coupling configuration and two currents that provide dynamic, voltage-gated, negative feedback in subthreshold voltage range: sodium current with rapid inactivation and low-threshold potassium current, IKLT. These currents reduce synaptic summation and can prevent spike generation unless inputs arrive with near simultaneity. We show that strong soma-to-axon coupling promotes the negative feedback effects of sodium inactivation and is, therefore, advantageous for coincidence detection. Furthermore, the “feedforward” combination of strong soma-to-axon coupling and weak axon-to-soma coupling enables spikes to be generated efficiently (few sodium channels needed) and with rapid recovery that enhances high-frequency coincidence detection. These observations detail the functional benefit of the strongly feedforward configuration that has been observed in physiological studies of MSO neurons. We find that IKLT further enhances coincidence detection sensitivity, but with effects that depend on coupling configuration. For instance, in weakly-coupled models, IKLT in the spike-generator compartment enhances coincidence detection more effectively than IKLT in the input compartment. By using a minimal model of soma-to-axon coupling, we connect structure, dynamics, and computation. Here, we consider the particular case of MSO coincidence detectors. In principle, our method for creating and exploring a parameter space of two-compartment models can be applied to other neurons.Author summaryBrain cells (neurons) are spatially extended structures. The locations at which neurons receive inputs and generate outputs are often distinct. We formulate and study a minimal mathematical model that describes the dynamical coupling between the input and output regions of a neuron. We construct our model to reflect known properties of neurons in the auditory brainstem that play an important role in our ability to locate sound sources. These neurons are known as “coincidence detectors” because they are most likely to respond when they receive simultaneous inputs. We use simulations to explore coincidence detection sensitivity throughout the parameter space of input-output coupling and to identify the coupling configurations that are best for neural coincidence detection. We find that strong forward coupling (from input region to output region), enhances coincidence detection sensitivity in our model and that low-threshold potassium current further improves coincidence detection. Our study is significant in that we detail how cell structure affects neuronal dynamics and, consequently, the ability of neurons to perform as temporally-precise coincidence detectors.

scholarly journals Auditory brainstem models: adapting cochlear nuclei improve spatial encoding by the medial superior olive in reverberation

2019 ◽  
Author(s):  
Andrew Brughera ◽  
Jason Mikiel-Hunter ◽  
Mathias Dietz ◽  
David McAlpine
Keyword(s):  
Spatial Information ◽  
Interaural Time Difference ◽  
Auditory Pathway ◽  
Auditory Brainstem ◽  
Coincidence Detection ◽  
Type Model ◽  
Medial Superior Olive ◽  
Sound Energy ◽  
Superior Olive ◽  
Cochlear Nuclei

AbstractListeners perceive sound-energy as originating from the direction of its source, even as direct sound is followed milliseconds later by reflected sound from multiple different directions. Early-arriving sound is emphasised in the ascending auditory pathway, including the medial superior olive (MSO) where binaural neurons encode the interaural time difference (ITD) cue for spatial location. Behaviourally, weighting of ITD conveyed during rising sound-energy is stronger at 600 Hz, a frequency with higher reverberant energy, than at 200 Hz where reverberant energy is lower. Here we computationally explore the combined effectiveness of adaptation before ITD-encoding, and excitatory binaural coincidence detection within MSO neurons, in emphasising ITD conveyed in early-arriving sound. With excitatory inputs from adapting model spherical bushy cells (SBCs) of the bilateral cochlear nuclei, a Hodgkin-Huxley-type model MSO neuron reproduces the frequency-dependent emphasis of rising vs. peak sound-energy in ITD-encoding. Maintaining the adaptation in model SBCs, and adjusting membrane speed in model MSO neurons, hemispheric populations of model SBCs and MSO neurons, with simplified membranes for computational efficiency, also reproduce the stronger weighting of ITD information conveyed during rising sound-energy at 600 Hz compared to 200 Hz. This hemispheric model further demonstrates a link between strong weighting of spatial information during rising sound-energy, and correct unambiguous lateralisation of reverberant speech.

scholarly journals Behavior and modeling of two-dimensional precedence effect in head-unrestrained cats

2015 ◽  
Vol 114 (2) ◽  
pp. 1272-1285
Author(s):  
Yan Gai ◽  
Janet L. Ruhland ◽  
Tom C. T. Yin
Keyword(s):  
Potassium Current ◽  
Horizontal Plane ◽  
Sagittal Plane ◽  
Precedence Effect ◽  
The Novel ◽  
Medial Superior Olive ◽  
Localization Dominance ◽  
Low Threshold ◽  
Spatial Locations ◽  
Auditory Illusion

The precedence effect (PE) is an auditory illusion that occurs when listeners localize nearly coincident and similar sounds from different spatial locations, such as a direct sound and its echo. It has mostly been studied in humans and animals with immobile heads in the horizontal plane; speaker pairs were often symmetrically located in the frontal hemifield. The present study examined the PE in head-unrestrained cats for a variety of paired-sound conditions along the horizontal, vertical, and diagonal axes. Cats were trained with operant conditioning to direct their gaze to the perceived sound location. Stereotypical PE-like behaviors were observed for speaker pairs placed in azimuth or diagonally in the frontal hemifield as the interstimulus delay was varied. For speaker pairs in the median sagittal plane, no clear PE-like behavior occurred. Interestingly, when speakers were placed diagonally in front of the cat, certain PE-like behavior emerged along the vertical dimension. However, PE-like behavior was not observed when both speakers were located in the left hemifield. A Hodgkin-Huxley model was used to simulate responses of neurons in the medial superior olive (MSO) to sound pairs in azimuth. The novel simulation incorporated a low-threshold potassium current and frequency mismatches to generate internal delays. The model exhibited distinct PE-like behavior, such as summing localization and localization dominance. The simulation indicated that certain encoding of the PE could have occurred before information reaches the inferior colliculus, and MSO neurons with binaural inputs having mismatched characteristic frequencies may play an important role.

Exploring parameter space in detailed single neuron models: simulations of the mitral and granule cells of the olfactory bulb

1993 ◽  
Vol 69 (6) ◽  
pp. 1948-1965 ◽  
Author(s):  
U. S. Bhalla ◽  
J. M. Bower
Keyword(s):  
Experimental Data ◽  
Olfactory Bulb ◽  
Parameter Space ◽  
Potassium Current ◽  
Granule Cells ◽  
Cell Model ◽  
Mitral Cell ◽  
Delayed Rectifier ◽  
Model Output ◽  
Parameter Variations

1. Detailed compartmental computer simulations of single mitral and granule cells of the vertebrate olfactory bulb were constructed using previously published geometric data. Electrophysiological properties were determined by comparing model output to previously published experimental data, mainly current-clamp recordings. 2. The passive electrical properties of each model were explored by comparing model output with intracellular potential data from hyperpolarizing current injection experiments. The results suggest that membrane resistivity in both cells is nonuniform, with somatas having a substantially lower resistivity than the dendrites. 3. The active properties of these cells were explored by incorporating active ion channels into modeled compartments. On the basis of evidence from the literature, the mitral cell model included six channel types: fast sodium, fast delayed rectifier (Kfast), slow delayed rectifier (K), transient outward potassium current (KA), voltage- and calcium-dependent potassium current (KCa), and L-type calcium current. The granule cell model included four channel types: rat brain sodium, K, KA, and the non-inactivating muscarinic potassium current (KM). Modeled channels were based on the Hodgkin-Huxley formalism. 4. Representative kinetics for each of the channel classes above were obtained from the literature. The experimentally unknown spatial distributions of each included channel were obtained by systematic parameter searches. These were conducted in two ways: large-scale simulation series, in which each parameter was varied in turn, and an adaptation of a multidimensional conjugate gradient method. In each case, the simulated results were compared wtih experimental data using a curve-matching function evaluating mean squared differences of several aspects of the simulated and experimental voltage waveforms. 5. Systematic parameter variations revealed a single distinct region of parameter space in which the mitral cell model best fit the data. This region of parameter space was also very robust to parameter variations. Specifically, optimum performance was obtained when calcium and slow K channels were concentrated in the glomeruli, with a lower density in the soma and proximal secondary dendrites. The distribution of sodium and fast potassium channels, on the other hand, was highest at the soma and axon, with a much lighter distribution throughout the secondary dendrites. The KA and KCa channels were also concentrated near the soma. 6. The parameter search of the granule cell model was much less restrained by experimental data. Several parameter regimes were found that gave a good match to the data.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Physiological and anatomical investigation of the auditory brainstem in the Fat-tailed Dunnart (Sminthopsis crassicaudata)

2019 ◽  
Author(s):  
Andrew Garrett ◽  
Virginia Lannigan ◽  
Nathanael Yates ◽  
Jennifer Rodger ◽  
Wilhelmina Mulders
Keyword(s):  
Auditory System ◽  
Mammalian Species ◽  
Auditory Brainstem ◽  
Auditory Brainstem Responses ◽  
Superior Olivary Complex ◽  
Medial Superior Olive ◽  
Superior Olive ◽  
Medial Nucleus ◽  
Sminthopsis Crassicaudata ◽  
Nissl Stain

The fat-tailed Dunnart (Sminthopsis crassicaudata) is a small (10-20g) native marsupial endemic to the south west of Western Australia. Currently little is known about the auditory capabilities of the dunnart, and of marsupials in general. Consequently, this study sought to investigate several electrophysiological and anatomical properties of the dunnart auditory system. Auditory brainstem responses (ABR) were recorded to brief (5ms) tone pips at a range of frequencies (4-47.5 kHz) and intensities to determine auditory brainstem thresholds. The dunnart ABR displayed multiple distinct peaks at all test frequencies, similar to other mammalian species. ABR showed the dunnart is most sensitive to higher frequencies increasing up to 47.5 kHz. Morphological observations (Nissl stain) revealed that the auditory structures thought to contribute to the first peaks of the ABR were all distinguishable in the dunnart. Structures identified include the dorsal and ventral subdivisions of the cochlear nucleus, including a cochlear nerve root nucleus as well as several distinct nuclei in the superior olivary complex, such as the medial nucleus of the trapezoid body, lateral superior olive and medial superior olive. This study is the first to show functional and anatomical aspects of the lower part of the auditory system in the Fat-tailed Dunnart.

scholarly journals A design of forceps-type coincidence radiation detector for intraoperative LN diagnosis: clinical impact estimated from LNs data of 20 esophageal cancer patients

2021 ◽  
Author(s):  
Miwako Takahashi ◽  
Shuntaro Yoshimura ◽  
Sodai Takyu ◽  
Susumu Aikou ◽  
Yasuhiro Okumura ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Radiation Detector ◽  
Radiation Detection ◽  
Statistical Error ◽  
Clinical Impact ◽  
Coincidence Detection ◽  
Detection Sensitivity ◽  
Scintillation Crystals ◽  
Positron Emission ◽  
Better Than

Abstract Purpose To reduce postoperative complications, intraoperative lymph node (LN) diagnosis with 18F-fluoro-2-deoxy-D-glucose (FDG) is expected to optimize the extent of LN dissection, leading to less invasive surgery. However, such a diagnostic device has not yet been realized. We proposed the concept of coincidence detection wherein a pair of scintillation crystals formed the head of the forceps. To estimate the clinical impact of this detector, we determined the cut-off value using FDG as a marker for intraoperative LN diagnosis in patients with esophageal cancer, the specifications needed for the detector, and its feasibility using numerical simulation. Methods We investigated the dataset including pathological diagnosis and radioactivity of 1073 LNs resected from 20 patients who underwent FDG-positron emission tomography followed by surgery for esophageal cancer on the same day. The specifications for the detector were determined assuming that it should measure 100 counts (less than 10% statistical error) or more within the intraoperative measurement time of 30 s. The detector sensitivity was estimated using GEANT4 simulation and the expected diagnostic ability was calculated. Results The cut-off value was 620 Bq for intraoperative LN diagnosis. The simulation study showed that the detector had a radiation detection sensitivity of 0.96%, which was better than the estimated specification needed for the detector. Among the 1035 non-metastatic LNs, 815 were below the cut-off value. Conclusion The forceps-type coincidence detector can provide sufficient sensitivity for intraoperative LN diagnosis. Approximately 80% of the prophylactic LN dissections in esophageal cancer can be avoided using this detector.

scholarly journals Protection of cochlear synapses from noise-induced excitotoxic trauma by blockade of Ca2+-permeable AMPA receptors

2020 ◽  
Vol 117 (7) ◽  
pp. 3828-3838 ◽  
Author(s):  
Ning Hu ◽  
Mark A. Rutherford ◽  
Steven H. Green
Keyword(s):  
Ampa Receptors ◽  
Spiral Ganglion ◽  
Auditory Brainstem ◽  
Spiral Ganglion Neurons ◽  
Loud Sound ◽  
Selective Blockade ◽  
Hearing Thresholds ◽  
Brainstem Response ◽  
Low Threshold ◽  
Ganglion Neurons

Exposure to loud sound damages the postsynaptic terminals of spiral ganglion neurons (SGNs) on cochlear inner hair cells (IHCs), resulting in loss of synapses, a process termed synaptopathy. Glutamatergic neurotransmission via α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type receptors is required for synaptopathy, and here we identify a possible involvement of GluA2-lacking Ca2+-permeable AMPA receptors (CP-AMPARs) using IEM-1460, which has been shown to block GluA2-lacking AMPARs. In CBA/CaJ mice, a 2-h exposure to 100-dB sound pressure level octave band (8 to 16 kHz) noise results in no permanent threshold shift but does cause significant synaptopathy and a reduction in auditory brainstem response (ABR) wave-I amplitude. Chronic intracochlear perfusion of IEM-1460 in artificial perilymph (AP) into adult CBA/CaJ mice prevented the decrease in ABR wave-I amplitude and the synaptopathy relative to intracochlear perfusion of AP alone. Interestingly, IEM-1460 itself did not affect the ABR threshold, presumably because GluA2-containing AMPARs can sustain sufficient synaptic transmission to evoke low-threshold responses during blockade of GluA2-lacking AMPARs. On individual postsynaptic densities, we observed GluA2-lacking nanodomains alongside regions with robust GluA2 expression, consistent with the idea that individual synapses have both CP-AMPARs and Ca2+-impermeable AMPARs. SGNs innervating the same IHC differ in their relative vulnerability to noise. We found local heterogeneity among synapses in the relative abundance of GluA2 subunits that may underlie such differences in vulnerability. We propose a role for GluA2-lacking CP-AMPARs in noise-induced cochlear synaptopathy whereby differences among synapses account for differences in excitotoxic susceptibility. These data suggest a means of maintaining normal hearing thresholds while protecting against noise-induced synaptopathy, via selective blockade of CP-AMPARs.

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