The emerging framework of mammalian auditory hindbrain development

Nothwang, Hans Gerd; Ebbers, Lena; Schlüter, Tina; Willaredt, Marc A.

doi:10.1007/s00441-014-2110-7

Cited by 21 publications

(15 citation statements)

References 189 publications

(242 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The formation of tonotopic gradients often depend on the interplay between molecular factors and neuronal activity [ 38 , 39 ]. Our analysis revealed that neuronal activity is required for the formation of this gradient, as the gradient is disrupted in deaf Cldn14 − / − mice.…”

Section: Discussionmentioning

confidence: 99%

Activity-dependent formation of a vesicular inhibitory amino acid transporter gradient in the superior olivary complex of NMRI mice

Ebbers¹,

Weber²,

Nothwang³

2017

BMC Neurosci

Self Cite

View full text Add to dashboard Cite

BackgroundIn the mammalian superior olivary complex (SOC), synaptic inhibition contributes to the processing of binaural sound cues important for sound localization. Previous analyses demonstrated a tonotopic gradient for postsynaptic proteins mediating inhibitory neurotransmission in the lateral superior olive (LSO), a major nucleus of the SOC. To probe, whether a presynaptic molecular gradient exists as well, we investigated immunoreactivity against the vesicular inhibitory amino acid transporter (VIAAT) in the mouse auditory brainstem.ResultsImmunoreactivity against VIAAT revealed a gradient in the LSO and the superior paraolivary nucleus (SPN) of NMRI mice, with high expression in the lateral, low frequency processing limb and low expression in the medial, high frequency processing limb of both nuclei. This orientation is opposite to the previously reported gradient of glycine receptors in the LSO. Other nuclei of the SOC showed a uniform distribution of VIAAT-immunoreactivity. No gradient was observed for the glycine transporter GlyT2 and the neuronal protein NeuN. Formation of the VIAAT gradient was developmentally regulated and occurred around hearing-onset between postnatal days 8 and 16. Congenital deaf Claudin14 −/− mice bred on an NMRI background showed a uniform VIAAT-immunoreactivity in the LSO, whereas cochlear ablation in NMRI mice after hearing-onset did not affect the gradient. Additional analysis of C57Bl6/J, 129/SvJ and CBA/J mice revealed a strain-specific formation of the gradient.ConclusionsOur results identify an activity-regulated gradient of VIAAT in the SOC of NRMI mice. Its absence in other mouse strains adds a novel layer of strain-specific features in the auditory system, i.e. tonotopic organization of molecular gradients. This calls for caution when comparing data from different mouse strains frequently used in studies involving transgenic animals. The presence of strain-specific differences offers the possibility of genetic mapping to identify molecular factors involved in activity-dependent developmental processes in the auditory system. This would provide an important step forward concerning improved auditory rehabilitation in cases of congenital deafness.

show abstract

Section: Discussionmentioning

confidence: 99%

Activity-dependent formation of a vesicular inhibitory amino acid transporter gradient in the superior olivary complex of NMRI mice

Ebbers¹,

Weber²,

Nothwang³

2017

BMC Neurosci

Self Cite

View full text Add to dashboard Cite

show abstract

“…A detailed analysis demonstrated that the volume reduction in the MNTB was due to cell death ( Fig 7 ). This cell death occurs during terminal postnatal differentiation, after completion of migration [ 12 ]. Interestingly, Crygn is thus required for survival after the previously established period between P0 and P4, in which a significant number of SOC neurons die in the absence of innervation [ 23 ] or postsynaptic Ca 2+ signaling [ 21 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

Functional Role of γ-Crystallin N in the Auditory Hindbrain

et al. 2016

Self Cite

View full text Add to dashboard Cite

γ-crystallins are major components of the vertebrate lens but show expression in other tissues as well. Their extralenticular functions remain so far unclear. Here, we explored such roles in the rodent superior olivary complex in which previous analysis demonstrated developmentally regulated expression of Crygd, Cryge and Crygn. Immunohistochemistry with novel antibodies against Crygd/e and Crygn indicate that expression of Crygd/e was moderate and varied between the perinatal superior olivary complex of mice, rats, and gerbils. Crygn-immunoreactivity was more robust and consistently highest in the medial nucleus of the trapezoid body, but also present in other nuclei of the superior olivary complex. To analyze the function of Crygn in the auditory hindbrain, we used a Crygn allele with a floxed exon 2. Upon pairing with Egr2::Cre mice, exon 2, encoding the first two greek key motifs of Crygn, was deleted in the developing auditory hindbrain. Anatomical analysis of these mice revealed a 20% volume reduction in the medial nucleus of the trapezoid body and a 7% reduction in the lateral superior olive at postnatal day 25. This was due to cell loss between postnatal days 4 and 25, whereas cell size was unaffected. Auditory brainstem responses showed normal threshold but a significant increase in the amplitude of wave IV. Crygn is hence required for postmigratory survival and proper function of auditory hindbrain neurons. These results ascertain for the first time an essential extralenticular role for γ-crystallins in vivo.

show abstract

“…An important role for exuberant connectivity seems to be to provide sufficient candidate precursors to ensure that each principal neuron will eventually end up being innervated by a calyx of Held from a globular bushy cell that innervates only a limited number of other principal neurons. As the molecular mechanisms underlying this process are gradually being elucidated (Hsieh et al 2010;Nakamura & Cramer, 2011;Ehmann et al 2013;Michalski et al 2013;Xiao et al 2013;Körber et al 2014;Yu & Goodrich, 2014;Nothwang et al 2015;Willaredt et al 2015;Dimitrov et al 2016;Radulovic et al 2020), to what extent postsynaptic activity plays a role in this selection process is still unclear. Without concurrent activity of other inputs, non-calyceal inputs are unable to evoke postsynaptic APs, as they elicit postsynaptic firing almost exclusively by EPSP summation (Sierksma et al 2016;this study).…”

Section: Calyceal Competition During Development?mentioning

confidence: 99%

Structure–function relation of the developing calyx of Held synapse in vivo

Sierksma

Slotman

Houtsmuller

et al. 2020

The Journal of Physiology

View full text Add to dashboard Cite

During development the giant, auditory calyx of Held forms a one-to-one connection with a principal neuron of the medial nucleus of the trapezoid body. r While anatomical studies described that most of the target cells are temporarily contacted by multiple calyces, multi-calyceal innervation was only sporadically observed in in vivo recordings, suggesting a structure-function discrepancy. r We correlated synaptic strength of inputs, identified in in vivo recordings, with post hoc labelling of the recorded neuron and synaptic terminals containing vesicular glutamate transporters (VGluT). r During development only one input increased to the level of the calyx of Held synapse, and its strength correlated with the large VGluT cluster contacting the postsynaptic soma. r As neither competing strong inputs nor multiple large VGluT clusters on a single cell were observed, our findings did not indicate a structure-function discrepancy.

show abstract

The emerging framework of mammalian auditory hindbrain development

Cited by 21 publications

References 189 publications

Activity-dependent formation of a vesicular inhibitory amino acid transporter gradient in the superior olivary complex of NMRI mice

Activity-dependent formation of a vesicular inhibitory amino acid transporter gradient in the superior olivary complex of NMRI mice

Functional Role of γ-Crystallin N in the Auditory Hindbrain

Structure–function relation of the developing calyx of Held synapse in vivo

Contact Info

Product

Resources

About