Inhibition in the auditory brainstem enhances signal representation and regulates gain in complex acoustic environments

Keine, Christian; Rübsamen, Rudolf; Englitz, Bernhard

doi:10.7554/elife.19295

Cited by 37 publications

(56 citation statements)

References 142 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For both cases the timing of EPSPs and spikes and rising slope of the EPSPs were 139 extracted. The timing and slope of the EPSPs were identified using a slope threshold for the rising 140 part of EPSPs as previously described (Keine et al, 2016). We then modeled spike transmission 141 probability patterns for two recordings: (i) during randomized pure tone acoustic stimulation and 142…”

Section: Neural Data 99mentioning

confidence: 99%

Modeling the short-term dynamics of in vivo excitatory spike transmission

Ghanbari

Ren

Keine

et al. 2018

Preprint

Self Cite

View full text Add to dashboard Cite

250 words) 14 Information transmission in neural networks is influenced by both short-term synaptic plasticity 15(STP) as well as non-synaptic factors, such as after-hyperpolarization currents and changes in 16 excitability. Although these effects have been widely characterized in vitro using intracellular 17 recordings, how they interact in vivo is unclear. Here we develop a statistical model of the short-18 term dynamics of spike transmission that aims to disentangle the contributions of synaptic and 19 non-synaptic effects based only on observed pre-and postsynaptic spiking. The model includes a 20 dynamic functional connection with short-term plasticity as well as effects due to the recent history 21 of postsynaptic spiking and slow changes in postsynaptic excitability. Using paired spike 22recordings, we find that the model accurately describes the short-term dynamics of in vivo spike 23 transmission at a diverse set of identified and putative excitatory synapses, including a 24 thalamothalamic connection in mouse, a thalamocortical connection in a female rabbit, and an 25 auditory brainstem synapse in a female gerbil. We illustrate the utility of this modeling approach 26by showing how the spike transmission patterns captured by the model may be sufficient to account 27for stimulus-dependent differences in spike transmission in the auditory brainstem (endbulb of 28 Held). Finally, we apply this model to large-scale multi-electrode recordings to illustrate how such 29 an approach has the potential to reveal cell-type specific differences in spike transmission in vivo. 30Although short-term synaptic plasticity parameters estimated from ongoing pre-and postsynaptic 31 spiking are highly uncertain, our results are partially consistent with previous intracellular 32 observations in these synapses. 33Significance Statement (120 words) 34 Although synaptic dynamics have been extensively studied and modeled using intracellular 35 recordings of post-synaptic currents and potentials, inferring synaptic effects from extracellular 36 spiking is challenging. Whether or not a synaptic current contributes to postsynaptic spiking 37 depends not only on the amplitude of the current, but also on many other factors, including the 38 activity of other, typically unobserved, synapses, the overall excitability of the postsynaptic 39 neuron, and how recently the postsynaptic neuron has spiked. Here we developed a model that, 40using only observations of pre-and postsynaptic spiking, aims to describe the dynamics of in vivo 41 spike transmission by modeling both short-term synaptic plasticity and non-synaptic effects. This 42 approach may provide a novel description of fast, structured changes in spike transmission. 43

show abstract

Section: Neural Data 99mentioning

confidence: 99%

Modeling the short-term dynamics of in vivo excitatory spike transmission

Ghanbari

Ren

Keine

et al. 2018

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…A number of inhibitory and secondary influences on BC that interact with the excitation have been identified (Oertel, ; Wickesberg & Oertel, ; Gómez‐Nieto & Rubio, ; Campagnola & Manis, ). Inhibition, for example, dynamically influences how the dominant excitatory inputs are processed by these neurons (Kopp‐Scheinpflug, Dehmel, Dörrscheidt, & Rübsamen, ; Kuenzel, Borst, & van der Heijden, ; Kuenzel, Nerlich, Wagner, Rübsamen, & Milenkovic, ; Nerlich et al, ; Keine & Rübsamen, ; Keine, Rübsamen, & Englitz, ). Furthermore, the CN is also targeted by descending modulatory inputs using acetylcholine as neurotransmitter (Comis & Davies, ; Sherriff & Henderson, ; Happe & Morley, ; Behrens, Schofield, & Thompson, ; Mellott, Motts, & Schofield, ).…”

Section: Introductionmentioning

confidence: 99%

“…2015; Nerlich et al, 2014;Keine & R€ ubsamen, 2015;Keine, R€ ubsamen, & Englitz, 2016). Furthermore, the CN is also targeted by descending modulatory inputs using acetylcholine as neurotransmitter (Comis & Davies, 1969;Sherriff & Henderson, 1994;Happe & Morley, 1998;Behrens, Schofield, & Thompson, 2002;.…”

mentioning

confidence: 99%

Cholinergic innervation of principal neurons in the cochlear nucleus of the Mongolian gerbil

Gillet

Goyer

Kurth

et al. 2018

J of Comparative Neurology

View full text Add to dashboard Cite

Principal neurons in the ventral cochlear nucleus (VCN) receive powerful ascending excitation and pass on the auditory information with exquisite temporal fidelity. Despite being dominated by ascending inputs, the VCN also receives descending cholinergic connections from olivocochlear neurons and from higher regions in the pontomesencephalic tegmentum. In Mongolian gerbils, acetylcholine acts as an excitatory and modulatory neurotransmitter on VCN neurons, but the anatomical structure of cholinergic innervation of gerbil VCN is not well described. We applied fluorescent immunohistochemical staining to elucidate the development and the cellular localization of presynaptic and postsynaptic components of the cholinergic system in the VCN of the Mongolian gerbil. We found that cholinergic fibers (stained with antibodies against the vesicular acetylcholine transporter) were present before hearing onset at P5, but innervation density increased in animals after P10. Early in development cholinergic fibers invaded the VCN from the medial side, spread along the perimeter and finally innervated all parts of the nucleus only after the onset of hearing. Cholinergic fibers ran in a rostro-caudal direction within the nucleus and formed en-passant swellings in the neuropil between principal neurons. Nicotinic and muscarinic receptors were expressed differentially in the VCN, with nicotinic receptors being mostly expressed in dendritic areas while muscarinic receptors were located predominantly in somatic membranes. These anatomical data support physiological indications that cholinergic innervation plays a role in modulating information processing in the cochlear nucleus.

show abstract

“…4, middle panel). We next searched for differences in the expression pattern of Gα i3 between Gnai3 gKOs and Gnai3 cKOs in retrocochlear regions possibly involved in neural gain generation at the level of the auditory nerve or its target neurons in the cochlear nucleus [59,60]. At the level of the spiral ganglion neurons (SGN) Gα i3 immunoreactivity was absent in Gnai3 gKO but not in Gnai3 cKO mice (Fig.…”

Section: Function Of Gα I3 In the Central Auditory Pathway Correlatesmentioning

confidence: 99%

Gαi Proteins are Indispensable for Hearing

Beer‐Hammer

Lee

Mauriac

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: From invertebrates to mammals, Gα_i proteins act together with their common binding partner Gpsm2 to govern cell polarization and planar organization in virtually any polarized cell. Recently, we demonstrated that Gα_i3-deficiency in pre-hearing murine cochleae pointed to a role of Gα_i3 for asymmetric migration of the kinocilium as well as the orientation and shape of the stereociliary (“hair”) bundle, a requirement for the progression of mature hearing. We found that the lack of Gα_i3 impairs stereociliary elongation and hair bundle shape in high-frequency cochlear regions, linked to elevated hearing thresholds for high-frequency sound. How these morphological defects translate into hearing phenotypes is not clear. Methods: Here, we studied global and conditional Gnai3 and Gnai2 mouse mutants deficient for either one or both Gα_i proteins. Comparative analyses of global versus Foxg1-driven conditional mutants that mainly delete in the inner ear and telencephalon in combination with functional tests were applied to dissect essential and redundant functions of different Gα_i isoforms and to assign specific defects to outer or inner hair cells, the auditory nerve, satellite cells or central auditory neurons. Results: Here we report that lack of Gα_i3 but not of the ubiquitously expressed Gα_i2 elevates hearing threshold, accompanied by impaired hair bundle elongation and shape in high-frequency cochlear regions. During the crucial reprogramming of the immature inner hair cell (IHC) synapse into a functional sensory synapse of the mature IHC deficiency for Gα_i2 or Gα_i3 had no impact. In contrast, double-deficiency for Gα_i2 and Gα_i3 isoforms results in abnormalities along the entire tonotopic axis including profound deafness associated with stereocilia defects. In these mice, postnatal IHC synapse maturation is also impaired. In addition, the analysis of conditional versus global Gα_i3-deficient mice revealed that the amplitude of ABR wave IV was disproportionally elevated in comparison to ABR wave I indicating that Gα_i3 is selectively involved in generation of neural gain during auditory processing. Conclusion: We propose a so far unrecognized complexity of isoform-specific and overlapping Gα_i protein functions particular during final differentiation processes.

show abstract

Inhibition in the auditory brainstem enhances signal representation and regulates gain in complex acoustic environments

Cited by 37 publications

References 142 publications

Modeling the short-term dynamics of in vivo excitatory spike transmission

Modeling the short-term dynamics of in vivo excitatory spike transmission

Cholinergic innervation of principal neurons in the cochlear nucleus of the Mongolian gerbil

Gαi Proteins are Indispensable for Hearing

Contact Info

Product

Resources

About