Activity-dependent, homeostatic regulation of neurotransmitter release from auditory nerve fibers

Information processing in the brain requires reliable synaptic transmission. High reliability at specialized auditory nerve synapses in the cochlear nucleus results from many release sites (N), high probability of neurotransmitter release (Pr), and large quantal size (Q). However, high Pr also causes auditory nerve synapses to depress strongly when activated at normal rates for a prolonged period, which reduces fidelity. We studied how synapses are influenced by prolonged activity by exposing mice to constant, nondamaging noise and found that auditory nerve synapses changed to facilitating, reflecting low Pr. For mice returned to quiet, synapses recovered to normal depression, suggesting that these changes are a homeostatic response to activity. Two additional properties, Q and average excitatory postsynaptic current (EPSC) amplitude, were unaffected by noise rearing, suggesting that the number of release sites (N) must increase to compensate for decreased Pr. These changes in N and Pr were confirmed physiologically using the integration method. Furthermore, consistent with increased N, endbulbs in noise-reared animals had larger VGlut1-positive puncta, larger profiles in electron micrographs, and more release sites per profile. In current-clamp recordings, noise-reared BCs had greater spike fidelity even during high rates of synaptic activity. Thus, auditory nerve synapses regulate excitability through an activity-dependent, homeostatic mechanism, which could have major effects on all downstream processing. Our results also suggest that noise-exposed bushy cells would remain hyperexcitable for a period after returning to normal quiet conditions, which could have perceptual consequences.

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Faculty Opinions recommendation of Activity-dependent, homeostatic regulation of neurotransmitter release from auditory nerve fibers.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725469677.793539250 ◽

2017 ◽

Author(s):

Tobias Moser ◽

Tanvi Butola

Keyword(s):

Auditory Nerve ◽

Neurotransmitter Release ◽

Nerve Fibers ◽

Homeostatic Regulation ◽

Auditory Nerve Fibers ◽

Activity Dependent

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Activity-dependent expression of reporter proteins at dendritic spines for synaptic activity mapping and optogenetic stimulation

10.1101/095984 ◽

2016 ◽

Author(s):

Francesco Gobbo ◽

Laura Marchetti ◽

Claudia Alia ◽

Stefano Luin ◽

Antonino Cattaneo

Keyword(s):

Dendritic Spines ◽

Cognitive Disorders ◽

Synaptic Activity ◽

Regulatory Sequences ◽

Synaptic Connections ◽

Optogenetic Stimulation ◽

Reporter Proteins ◽

Activity Dependent ◽

The Brain ◽

Spine Number

Increasing evidence points to the importance of dendritic spines in the formation and allocation of memories, and alterations of spine number and physiology are associated to memory and cognitive disorders. Synaptic connections and pathways constitute the physical substrate that conveys information in the brain, and different combinations of active synaptic connections are believed to be responsible for the encoding of specific memories. In addition, modifications of the activity of such subsets of synapses are believed to be crucial for memory establishment, but a way to directly test this hypothesis, by selectively controlling the activity of potentiated spines, is currently lagging behind. Therefore it would be important to develop methods to tag active synapses for mapping functionally active connections and to selectively stimulate or interfere with active synapses. Here we introduce an approach to express light-sensitive membrane channels at synapses in an activity-dependent way by means of RNA and protein regulatory sequences. This approach is based on the local expression of reporter proteins, including optogenetic probes, at activated synapses and will allow the mapping of previously active synapses and the re-activation of the neuron only at these sites. This will allow extending the investigation of memory processes beyond the current neuron tagging technologies, whose resolution is limited at the cellular scale. Thus, it will be possible to unveil and recall the synaptic engram out of the global set of synapses.

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Biomechanics of Hearing Sensitivity

Journal of Vibration and Acoustics ◽

10.1115/1.2930149 ◽

1991 ◽

Vol 113 (1) ◽

pp. 1-13 ◽

Cited By ~ 31

Author(s):

Sir James Lighthill

Keyword(s):

Hair Cells ◽

Auditory Nerve ◽

Basilar Membrane ◽

Nerve Fibers ◽

Outer Hair Cells ◽

Hearing Sensitivity ◽

Sound Levels ◽

Auditory Nerve Fibers ◽

The Brain ◽

Stiffness Distribution

This survey lecture on the biomechanics of hearing sensitivity is concerned, not with how the brain in man and other mammals analyzes the data coming to it along auditory nerve fibers, but with the initial capture of that data in the cochlea. The brain, needless to say, can produce all its miracles of interpretation only where it works on good initial data. For frequency selectivity these depend on some remarkable properties of the cochlea as a passive macromechanical system, comprising the basilar membrane with its steeply graded stiffness distribution vibrating within the cochlear fluids. But the biomechanics of hearing sensitivity to low levels of sound (at any particular frequency) calls also into play an active micromechanical system, which during the past few years has progressively been identified as located in the outer hair cells, and which, through a process of positive feedback, amplifies (in healthy ears) that basilar membrane vibration. This in turn offers the inner hair cells an enhanced signal at low sound levels, so that the threshold at which they can generate activity in auditory nerve fibers is, in consequence, very substantially lowered.

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ADAR2 mediated Q/R editing of GluK2 regulates homeostatic plasticity of kainate receptors

10.1101/308650 ◽

2018 ◽

Cited By ~ 1

Author(s):

Sonam Gurung ◽

Ashley J. Evans ◽

Kevin A. Wilkinson ◽

Jeremy M. Henley

Keyword(s):

Neuronal Excitability ◽

Surface Expression ◽

Synaptic Activity ◽

Homeostatic Plasticity ◽

Kainate Receptors ◽

Mrna Editing ◽

Network Function ◽

Pore Lining ◽

Activity Dependent ◽

The Brain

AbstractKainate receptors (KARs) are heteromeric glutamate-gated ion channels that regulate neuronal excitability and network function in the brain. Most KARs contain the subunit GluK2 and the precise properties of these GluK2-containing KARs are determined by additional factors including ADAR2-mediated mRNA editing of a single codon that changes a genomically encoded glutamine (Q) to arginine (R) in the pore-lining region of GluK2. ADAR2-dependent Q/R editing of GluK2 is dynamically regulated during homeostatic plasticity (scaling) elicited by suppression of synaptic activity with TTX. Here we show that TTX decreases levels of ADAR2 by enhancing its proteasomal degradation. This selectively reduces the numbers of GluK2 subunits that are edited and increases the surface expression of GluK2-containing KARs. Furthermore, we show that partial ADAR2 knockdown phenocopies and occludes TTX-induced scaling of KARs. These data indicate that activity-dependent regulation of ADAR2 proteostasis and GluK2 Q/R editing provides a mechanism for KAR homeostatic plasticity.

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Repetitive synaptic activity leads to calcium-dependent secretion of endogenous CGRP and subsequent increase of quantal size in mouse neuromuscular junctions

10.26226/morressier.5b31ec572afeeb001345a1f2 ◽

2018 ◽

Author(s):

Polina Bogatcheva

Keyword(s):

Neuromuscular Junctions ◽

Synaptic Activity ◽

Subsequent Increase ◽

Calcium Dependent ◽

Quantal Size

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Pelvic schwannoma

GYNECOLOGY ◽

10.26442/20795696.2020.5.200216 ◽

2020 ◽

Vol 22 (5) ◽

pp. 84-86

Author(s):

Sergei P. Sinchikhin ◽

Sarkis G. Magakyan ◽

Oganes G. Magakyan

Keyword(s):

Auditory Nerve ◽

World Literature ◽

Morphological Study ◽

Clinical Observation ◽

Nerve Trunk ◽

Practical Case ◽

Surgical Volume ◽

The World ◽

Brain And Spinal Cord ◽

The Brain

Relevance.A neoplasm originated from the myelonic sheath of the nerve trunk is called neurinoma or neurilemmoma, neurinoma, schwannoglioma, schwannoma. This tumor can cause compression and dysfunction of adjacent tissues and organs. The most common are the auditory nerve neurinomas (1 case per 100 000 population per year), the brain and spinal cord neurinomas are rare. In the world literature, there is no information on the occurrences of this tumor in the pelvic region. Description.Presented below is a clinical observation of a 30-year-old patient who was scheduled for myomectomy. During laparoscopy, an unusual tumor of the small pelvis was found and radically removed. A morphological study allowed to identify the remote neoplasm as a neuroma. Conclusion.The presented practical case shows that any tumor can hide under a clinical mask of another disease. The qualification of the doctor performing laparoscopic myomectomy should be sufficient to carry out, if necessary, another surgical volume.

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