Development of synaptic fidelity and action potential robustness at an inhibitory sound localization circuit: effects of otoferlin‐related deafness

Müller, Nicolas I. C.; Paulußen, Isabelle; Hofmann, Lina N; Fisch, Jonas O; Singh, Abhyudai; Friauf, Eckhard

doi:10.1113/jp280403

Cited by 5 publications

(4 citation statements)

References 126 publications

(200 reference statements)

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“…We performed electrophysiological experiments in acute brainstem slices of juvenile mice (postnatal day 11) at MNTB-LSO synapses. These fast auditory synapses transfer inhibitory glycinergic information and can maintain reliable neurotransmission even during prolonged high-frequency stimulation [39, 40]. We refer the reader to the Methods section of Ref.…”

Section: Methodsmentioning

confidence: 99%

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Exact distribution of the quantal content in synaptic transmission

Rijal

Müller

Friauf

et al. 2022

Preprint

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The transfer of electro-chemical signals from the pre-synaptic to the post-synaptic terminal of a neuronal or neuro-muscular synapse is the basic building block of neuronal communication. When triggered by an action potential the pre-synaptic terminal releases neurotransmitters in the synaptic cleft through vesicle fusion. The number of vesicles that fuse, i.e., the burst size, is stochastic, and widely assumed to be binomially distributed. However, the burst size depends on the number of release-ready vesicles, a random variable that depends upon a stochastic replenishment process, as well as stochastic inter-spike intervals of action potentials. The burst size distribution suitably averaged over these two stochastic processes was not known in the literature. Here we analytically obtain the exact probability distribution of the number of vesicles released in the synaptic cleft, in the steady state reached during stimulation by a spike train of action potentials. We show that this distribution is binomial, with modified parameters, only when stimulated by constant frequency signals. Other forms of input, e.g. Poisson-distributed action potentials, lead to distributions that are non-binomial. The general formula valid for arbitrary distributions of the input inter-spike interval, may be employed to study neuronal transmission under diverse experimental conditions. We corroborate our theoretical predictions through comparison with the burst size distributions obtained from electrophysiological recordings from MNTB-LSO synapses of juvenile mice. We also confirm our theoretically predicted frequency dependence of mean burst size by comparing with experimental data from hippocampal and auditory neurons.

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Section: Methodsmentioning

confidence: 99%

“…We refer the reader to the Methods section of Ref. [40] for details on the slice preparation and details of whole-cell patch-clamp recordings. The stimulation protocol consisted of repetitive tetanic AP bursts (100 Hz, 1 s) that were given 20 times.…”

Section: Methodsmentioning

confidence: 99%

Exact distribution of the quantal content in synaptic transmission

Rijal

Müller

Friauf

et al. 2022

Preprint

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“…Like other auditory brainstem structures, the DNLL undergoes changes in biophysical and synaptic properties during postnatal development leading to faster information transfer and higher excitability (Ahuja & Wu, 2000; Ammer et al, 2012). Developmental, postnatal changes in synaptic transmission have been reported in the ventral nucleus of the lateral lemniscus (Baumann & Koch, 2017; Kladisios et al, 2020), the medial superior olive (Franzen et al, 2020; Kladisios et al, 2020; Magnusson et al, 2005; Scott et al, 2005), the medial nucleus of the trapezoid body (Iwasaki & Takahashi, 2001; Joshi et al, 2004; Kladisios et al, 2020; Taschenberger & von Gersdorff, 2000), the lateral superior olive (Alamilla & Gillespie, 2013; Kandler & Friauf, 1995; Muller et al, 2022; Walcher et al, 2011) and the anterior ventral cochlear nucleus (Yang & Xu‐Friedman, 2010). These changes include the size, shape and short‐term plasticity of postsynaptic currents as well as the expression patterns of voltage‐gated ion channels.…”

Section: Introductionmentioning

confidence: 99%

GABA_B receptor‐mediated modulation in the developing dorsal nucleus of the lateral lemniscus

Javadova,

Felmy

2024

Eur J of Neuroscience

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The dorsal nucleus of the lateral lemniscus (DNLL) is a GABAergic, reciprocally connected auditory brainstem structure that continues to develop postnatally in rodents. One key feature of the DNLL is the generation of a strong, prolonged, ionotropic, GABAA receptor‐mediated inhibition. Possible GABAB receptor‐mediated signalling is unexplored in the DNLL. Here, we used Mongolian gerbils of either sex to describe GABAB receptor‐mediated modulation of postsynaptic potassium currents and synaptic inputs in postnatal (P) animals of days 10/11 and 23–28. Throughout development, we observed the presence of a Baclofen‐activated GABAB receptor‐enhanced potassium outward conductance that is capable of suppressing action potential generation. In P10/11, old gerbils GABAB receptor activation enhances glutamatergic and suppresses ionotropic GABAergic synaptic transmission. During development, this differential modulation becomes less distinct, because in P22–28, old animals Baclofen‐activated GABAB receptors rather enhance ionotropic GABAergic synaptic transmission, whereas glutamatergic transmission is both enhanced and suppressed. Blocking GABAB receptors causes an increase in ionotropic GABAergic transmission in P10/11 old gerbils that was independent on stimulation frequency but depended on the type of short‐term plasticity. Together with the lack of Baclofen‐induced changes in the synaptic paired‐pulse ratio of either input type, we suggest that GABAB receptor‐mediated modulation is predominantly postsynaptic and activates different signalling cascades. Thus, we argue that in DNLL neurons, the GABAB receptor is a post‐synaptically located signalling hub that alters signalling cascades during development for distinct targets.

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“…The main inputs are in strict tonotopic register and are glutamatergic, respectively, glycinergic with modulatory GABAergic inputs ( Fischer et al, 2019 ). Collectively, these inputs are tuned for fast and precise synaptic transmission, even during sustained high-frequency stimulation ( Krächan et al, 2017 ; Müller et al, 2022 ). pLSOs in mice have fusiform somata with a surface area of ~130 μm 2 ( Williams et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Molecular and functional profiling of cell diversity and identity in the lateral superior olive, an auditory brainstem center with ascending and descending projections

Maraslioglu-Sperber,

Pizzi,

Fisch

et al. 2024

Front. Cell. Neurosci.

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The lateral superior olive (LSO), a prominent integration center in the auditory brainstem, contains a remarkably heterogeneous population of neurons. Ascending neurons, predominantly principal neurons (pLSOs), process interaural level differences for sound localization. Descending neurons (lateral olivocochlear neurons, LOCs) provide feedback into the cochlea and are thought to protect against acoustic overload. The molecular determinants of the neuronal diversity in the LSO are largely unknown. Here, we used patch-seq analysis in mice at postnatal days P10-12 to classify developing LSO neurons according to their functional and molecular profiles. Across the entire sample (n = 86 neurons), genes involved in ATP synthesis were particularly highly expressed, confirming the energy expenditure of auditory neurons. Two clusters were identified, pLSOs and LOCs. They were distinguished by 353 differentially expressed genes (DEGs), most of which were novel for the LSO. Electrophysiological analysis confirmed the transcriptomic clustering. We focused on genes affecting neuronal input–output properties and validated some of them by immunohistochemistry, electrophysiology, and pharmacology. These genes encode proteins such as osteopontin, Kv11.3, and Kvβ3 (pLSO-specific), calcitonin-gene-related peptide (LOC-specific), or Kv7.2 and Kv7.3 (no DEGs). We identified 12 “Super DEGs” and 12 genes showing “Cluster similarity.” Collectively, we provide fundamental and comprehensive insights into the molecular composition of individual ascending and descending neurons in the juvenile auditory brainstem and how this may relate to their specific functions, including developmental aspects.

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Development of synaptic fidelity and action potential robustness at an inhibitory sound localization circuit: effects of otoferlin‐related deafness

Cited by 5 publications

References 126 publications

Exact distribution of the quantal content in synaptic transmission

Exact distribution of the quantal content in synaptic transmission

GABA_B receptor‐mediated modulation in the developing dorsal nucleus of the lateral lemniscus

Molecular and functional profiling of cell diversity and identity in the lateral superior olive, an auditory brainstem center with ascending and descending projections

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Development of synaptic fidelity and action potential robustness at an inhibitory sound localization circuit: effects of otoferlin‐related deafness

Cited by 5 publications

References 126 publications

Exact distribution of the quantal content in synaptic transmission

Exact distribution of the quantal content in synaptic transmission

GABAB receptor‐mediated modulation in the developing dorsal nucleus of the lateral lemniscus

Molecular and functional profiling of cell diversity and identity in the lateral superior olive, an auditory brainstem center with ascending and descending projections

Contact Info

Product

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GABA_B receptor‐mediated modulation in the developing dorsal nucleus of the lateral lemniscus