Extraction of Auditory Information by Modulation of Neuronal Ion Channels

The Oxford Handbook of the Auditory Brainstem ◽

10.1093/oxfordhb/9780190849061.013.23 ◽

2018 ◽

pp. 272-300

Author(s):

Leonard K. Kaczmarek

Keyword(s):

Ion Channels ◽

Neuronal Firing ◽

Auditory Information ◽

Auditory Neurons ◽

Complex Sound ◽

Medial Nucleus ◽

Rapid Changes ◽

Genes Encoding ◽

Kinetics Of ◽

Trapezoid Body

All neurons express a subset of over seventy genes encoding potassium channel subunits. These channels have been studied in auditory neurons, particularly in the medial nucleus of the trapezoid body. The amplitude and kinetics of various channels in these neurons can be modified by the auditory environment. It has been suggested that such modulation is an adaptation of neuronal firing patterns to specific patterns of auditory inputs. Alternatively, such modulation may allow a group of neurons, all expressing the same set of channels, to represent a variety of responses to the same pattern of incoming stimuli. Such diversity would ensure that a small number of genetically identical neurons could capture and encode many aspects of complex sound, including rapid changes in timing and amplitude. This review covers the modulation of ion channels in the medial nucleus of the trapezoid body and how it may maximize the extraction of auditory information.All neurons express a subset of over seventy genes encoding potassium channel subunits. These channels have been studied in auditory neurons, particularly in the medial nucleus of the trapezoid body. The amplitude and kinetics of various channels in these neurons can be modified by the auditory environment. It has been suggested that such modulation is an adaptation of neuronal firing patterns to specific patterns of auditory inputs. Alternatively, such modulation may allow a group of neurons, all expressing the same set of channels, to represent a variety of responses to the same pattern of incoming stimuli. Such diversity would ensure that a small number of genetically identical neurons could capture and encode many aspects of complex sound, including rapid changes in timing and amplitude. This review covers the modulation of ion channels in the medial nucleus of the trapezoid body and how it may maximize the extraction of auditory information.

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Glycinergic inhibition to the medial nucleus of the trapezoid body shows prominent facilitation and can sustain high levels of ongoing activity

Journal of Neurophysiology ◽

10.1152/jn.00864.2013 ◽

2014 ◽

Vol 112 (11) ◽

pp. 2901-2915 ◽

Cited By ~ 9

Author(s):

Florian Mayer ◽

Otto Albrecht ◽

Anna Dondzillo ◽

Achim Klug

Keyword(s):

Meriones Unguiculatus ◽

Inhibitory Synapses ◽

Auditory Information ◽

Activity Levels ◽

Synaptic Currents ◽

Medial Nucleus ◽

Highly Active ◽

Glycinergic Inhibition ◽

Trapezoid Body

Neurons in the medial nucleus of the trapezoid body (MNTB) are well known for their prominent excitatory inputs, mediated by the calyx of Held. Less attention has been paid to the prominent inhibitory inputs that MNTB neurons also receive. Because of their auditory nature, both excitatory and inhibitory synapses are highly active in vivo. These high levels of activity are known to reduce excitatory synaptic currents considerably, such that in vivo synaptic currents produced by the calyx are smaller than typically measured in standard brain slice experiments. The goal of this study was to investigate the properties of the inhibitory inputs in the Mongolian gerbil ( Meriones unguiculatus) under activity levels that correspond to those in the intact brain to facilitate a direct comparison between the two inputs. Our results suggest that inhibitory inputs to MNTB are largely mediated by a fast and phasic glycinergic component, and to a lesser degree by a GABAergic component. The glycinergic component can sustain prolonged high levels of activity. Even when challenged with stimulus patterns consisting of thousands of stimuli over tens of minutes, glycinergic inputs to MNTB maintain large conductances and fast decays and even facilitate substantially when the stimulation frequency is increased. The inhibition is mediated by a relatively small number of independent input fibers. The data presented here suggest that inhibitory inputs to MNTB sustain high levels of activity and need to be considered for a full understanding of mechanisms underlying processing of auditory information in MNTB.

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Seizures and Reduced Life Span in Mice Lacking the Potassium Channel Subunit Kv1.2, but Hypoexcitability and Enlarged Kv1 Currents in Auditory Neurons

Journal of Neurophysiology ◽

10.1152/jn.00640.2006 ◽

2007 ◽

Vol 98 (3) ◽

pp. 1501-1525 ◽

Cited By ~ 101

Author(s):

Helen M. Brew ◽

Joshua X. Gittelman ◽

Robert S. Silverstein ◽

Timothy D. Hanks ◽

Vas P. Demas ◽

...

Keyword(s):

Potassium Channel ◽

Low Voltage ◽

Seizure Susceptibility ◽

Auditory Neurons ◽

Medial Nucleus ◽

Voltage Dependent ◽

Similar Phenotype ◽

Brain Stem Slices ◽

Trapezoid Body ◽

Fine Tune

Genes Kcna1 and Kcna2 code for the voltage-dependent potassium channel subunits Kv1.1 and Kv1.2, which are coexpressed in large axons and commonly present within the same tetramers. Both contribute to the low-voltage–activated potassium current IKv1, which powerfully limits excitability and facilitates temporally precise transmission of information, e.g., in auditory neurons of the medial nucleus of the trapezoid body (MNTB). Kcna1-null mice lacking Kv1.1 exhibited seizure susceptibility and hyperexcitability in axons and MNTB neurons, which also had reduced IKv1. To explore whether a lack of Kv1.2 would cause a similar phenotype, we created and characterized Kcna2-null mice (−/−). The −/− mice exhibited increased seizure susceptibility compared with their +/+ and +/− littermates, as early as P14. The mRNA for Kv1.1 and Kv1.2 increased strongly in +/+ brain stems between P7 and P14, suggesting the increasing importance of these subunits for limiting excitability. Surprisingly, MNTB neurons in brain stem slices from −/− and +/− mice were hypoexcitable despite their Kcna2 deficit, and voltage-clamped −/− MNTB neurons had enlarged IKv1. This contrasts strikingly with the Kcna1-null MNTB phenotype. Toxin block experiments on MNTB neurons suggested Kv1.2 was present in every +/+ Kv1 channel, about 60% of +/− Kv1 channels, and no −/− Kv1 channels. Kv1 channels lacking Kv1.2 activated at abnormally negative potentials, which may explain why MNTB neurons with larger proportions of such channels had larger IKv1. If channel voltage dependence is determined by how many Kv1.2 subunits each contains, neurons might be able to fine-tune their excitability by adjusting the Kv1.1:Kv1.2 balance rather than altering Kv1 channel density.

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Signal processing in brainstem auditory neurons which receive giant endings (calyces of Held) in the medial nucleus of the trapezoid body of the cat

Hearing Research ◽

10.1016/0378-5955(90)90111-2 ◽

1990 ◽

Vol 49 (1-3) ◽

pp. 321-334 ◽

Cited By ~ 95

Author(s):

John J Guinan ◽

Robert Y.-S Li

Keyword(s):

Signal Processing ◽

Auditory Neurons ◽

Medial Nucleus ◽

Trapezoid Body

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Linear coding of complex sound spectra by discharge rate in neurons of the medial nucleus of the trapezoid body (MNTB) and its inputs

Frontiers in Neural Circuits ◽

10.3389/fncir.2014.00144 ◽

2014 ◽

Vol 8 ◽

Cited By ~ 10

Author(s):

Kanthaiah Koka ◽

Daniel J. Tollin

Keyword(s):

Discharge Rate ◽

Complex Sound ◽

Medial Nucleus ◽

Trapezoid Body

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The Auditory Brainstem Implant

The Oxford Handbook of the Auditory Brainstem ◽

10.1093/oxfordhb/9780190849061.013.28 ◽

2019 ◽

pp. 758-770

Author(s):

Robert V. Shannon

Keyword(s):

Surgical Technique ◽

Cochlear Nucleus ◽

Meta Analysis ◽

Auditory Brainstem ◽

Auditory Information ◽

Speech Understanding ◽

Auditory Neurons ◽

Auditory Brainstem Implant ◽

The Brain ◽

Implanted Device

The auditory brainstem implant (ABI) is a surgically implanted device to electrically stimulate auditory neurons in the cochlear nucleus complex of the brainstem in humans to restore hearing sensations. The ABI is similar in function to a cochlear implant, but overall outcomes are poorer. However, recent applications of the ABI to new patient populations and improvements in surgical technique have led to significant improvements in outcomes. While the ABI provides hearing benefits to patients, the outcomes challenge our understanding of how the brain processes neural patterns of auditory information. The neural pattern of activation produced by an ABI is highly unnatural, yet some patients achieve high levels of speech understanding. Based on a meta-analysis of ABI surgeries and outcomes, a theory is proposed of a specialized sub-system of the cochlear nucleus that is critical for speech understanding.

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Acute O2 sensing through HIF2α-dependent expression of atypical cytochrome oxidase subunits in arterial chemoreceptors

Science Signaling ◽

10.1126/scisignal.aay9452 ◽

2019 ◽

Vol 13 (615) ◽

pp. eaay9452 ◽

Cited By ~ 9

Author(s):

Alejandro Moreno-Domínguez ◽

Patricia Ortega-Sáenz ◽

Lin Gao ◽

Olalla Colinas ◽

Paula García-Flores ◽

...

Keyword(s):

Ion Channels ◽

Carotid Body ◽

Acute Hypoxia ◽

Mechanistic Explanation ◽

Nerve Fibers ◽

Adaptive Responses ◽

Glomus Cells ◽

Adult Mice ◽

Genes Encoding ◽

Regulation Of Breathing

Acute cardiorespiratory responses to O2 deficiency are essential for physiological homeostasis. The prototypical acute O2-sensing organ is the carotid body, which contains glomus cells expressing K+ channels whose inhibition by hypoxia leads to transmitter release and activation of nerve fibers terminating in the brainstem respiratory center. The mechanism by which changes in O2 tension modulate ion channels has remained elusive. Glomus cells express genes encoding HIF2α (Epas1) and atypical mitochondrial subunits at high levels, and mitochondrial NADH and reactive oxygen species (ROS) accumulation during hypoxia provides the signal that regulates ion channels. We report that inactivation of Epas1 in adult mice resulted in selective abolition of glomus cell responsiveness to acute hypoxia and the hypoxic ventilatory response. Epas1 deficiency led to the decreased expression of atypical mitochondrial subunits in the carotid body, and genetic deletion of Cox4i2 mimicked the defective hypoxic responses of Epas1-null mice. These findings provide a mechanistic explanation for the acute O2 regulation of breathing, reveal an unanticipated role of HIF2α, and link acute and chronic adaptive responses to hypoxia.

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GABA is a modulator, rather than a classical transmitter, in the medial nucleus of the trapezoid body–lateral superior olive sound localization circuit

The Journal of Physiology ◽

10.1113/jp277566 ◽

2019 ◽

Vol 597 (8) ◽

pp. 2269-2295 ◽

Cited By ~ 5

Author(s):

Alexander U. Fischer ◽

Nicolas I. C. Müller ◽

Thomas Deller ◽

Domenico Del Turco ◽

Jonas O. Fisch ◽

...

Keyword(s):

Sound Localization ◽

Lateral Superior Olive ◽

Superior Olive ◽

Medial Nucleus ◽

Trapezoid Body

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The principal neurons of the medial nucleus of the trapezoid body and NG2+ glial cells receive coordinated excitatory synaptic input

The Journal of General Physiology ◽

10.1085/jgp.200910194 ◽

2009 ◽

Vol 134 (2) ◽

pp. 115-127 ◽

Cited By ~ 48

Author(s):

Jochen Müller ◽

Daniel Reyes-Haro ◽

Tatjyana Pivneva ◽

Christiane Nolte ◽

Roland Schaette ◽

...

Keyword(s):

Glial Cell ◽

Glial Cells ◽

Synaptic Input ◽

Medial Nucleus ◽

Synaptic Structure ◽

Excitatory Synaptic Input ◽

Cell Processes ◽

To Receive ◽

Trapezoid Body ◽

Axosomatic Synapse

Glial cell processes are part of the synaptic structure and sense spillover of transmitter, while some glial cells can even receive direct synaptic input. Here, we report that a defined type of glial cell in the medial nucleus of the trapezoid body (MNTB) receives excitatory glutamatergic synaptic input from the calyx of Held (CoH). This giant glutamatergic terminal forms an axosomatic synapse with a single principal neuron located in the MNTB. The NG2 glia, as postsynaptic principal neurons, establish synapse-like structures with the CoH terminal. In contrast to the principal neurons, which are known to receive excitatory as well as inhibitory inputs, the NG2 glia receive mostly, if not exclusively, α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptor–mediated evoked and spontaneous synaptic input. Simultaneous recordings from neurons and NG2 glia indicate that they partially receive synchronized spontaneous input. This shows that an NG2+ glial cell and a postsynaptic neuron share presynaptic terminals.

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Perinatal Development of the Medial Nucleus of the Trapezoid Body

The Oxford Handbook of the Auditory Brainstem ◽

10.1093/oxfordhb/9780190849061.013.22 ◽

2018 ◽

pp. 244-272

Author(s):

Shobhana Sivaramakrishnan ◽

Ashley Brandebura ◽

Paul Holcomb ◽

Daniel Heller ◽

Douglas Kolson ◽

...

Keyword(s):

Axon Guidance ◽

Neural Circuit ◽

Neural Cells ◽

Calyx Of Held ◽

Medial Nucleus ◽

Target Neuron ◽

Circuit Formation ◽

Key Events ◽

The Brain ◽

Trapezoid Body

Bushy cells (BC) of the cochlear nucleus mono-innervate their target neuron, the principal cell of the medial nucleus of the trapezoid body (MNTB), via the calyx of Held (CH) terminal, which is a typically mammalian structure and perhaps the largest nerve terminal in the brain. CH:MNTB innervation has become an attractive model to study neural circuit formation because it forms quickly, passing through stages of competition in mice within 2–4 days. BCs innervate MNTB neurons by E17, but CHs do not begin to grow for another five days (P3). Progress has been made to identify molecular factors for axon guidance, CH growth, and physiological maturation of synaptic partners, but important details remain to be discovered. We summarize key events in CH formation and highlight unresolved issues in molecular and physiological signaling, roles for non-neural cells, and the nature of competition during the first postnatal week.

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