Olivocochlear Neuron Central Anatomy Is Normal in α9 Knockout Mice

Brown, M. Christian; Vetter, Douglas E.

doi:10.1007/s10162-008-0144-9

Cited by 15 publications

(13 citation statements)

References 45 publications

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“…This trend became more noticeable after the onset of hearing (P15; Figure b): all parts of the nucleus, including the central and lateral areas, now showed VAChT‐positive punctae, with the medial border being most densely innervated. This pattern is similar to cholinergic innervation patterns reported by other authors in the VCN of rodents (Ryan et al, ; Brown & Vetter, ; Baashar et al, ). Finally, however, in P28 animals all parts of the AVCN showed strong occurrence of VAChT‐positive punctae (Figure b), with the highest density now located closer to the core of the AVCN towards the latero‐ventral side of the AVCN.…”

Section: Resultssupporting

confidence: 91%

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

Gillet

Goyer

Kurth

et al. 2018

J of Comparative Neurology

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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.

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Section: Resultssupporting

confidence: 91%

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

Gillet

Goyer

Kurth

et al. 2018

J of Comparative Neurology

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“…Since OHC loss results in the loss of the post-synaptic targets of the MOC neurons, this may stimulate compensatory regenerative mechanisms in MOC neurons causing them to establish new synapses in the VCN. However, Brown and Vetter (2008) found no increase of MOC innervation to the VCN despite nonfunctional MOC-synapses on OHC in the α9 knock-out mouse, making the hypothesis of central MOC synapse sprouting as a compensation mechanism for lost cochlear innervation less attractive. Thus, OHC loss alone appears unlikely to trigger synapse sprouting in VCN, but may require additional conditions to occur.…”

Section: Discussionmentioning

confidence: 87%

Up-regulation of GAP-43 in the chinchilla ventral cochlear nucleus after carboplatin-induced hearing loss: Correlations with inner hair cell loss and outer hair cell loss

Kraus¹,

Ding²,

Jiang³

et al. 2013

Hearing Research

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Inner ear damage leads to nerve fiber growth and synaptogenesis in the ventral cochlear nucleus (VCN). In this study, we documented the relationship between hair cell loss patterns and synaptic plasticity in the chinchilla VCN using immunolabeling of the growth associated protein-43 (GAP-43), a protein associated with axon outgrowth and modification of presynaptic endings. Unilateral round window application of carboplatin caused hair cell degeneration in which inner hair cells (IHC) were more vulnerable than outer hair cells (OHC). One month after carboplatin treatment (0.5 to 5 mg/ml), we observed varying patterns of cochlear hair cell loss and GAP-43 expression in VCN. Both IHC loss and OHC loss were strongly correlated with increased GAP-43 immunolabeling in the ipsilateral VCN. We speculate that two factors might promote the expression of GAP-43 in the VCN; one is the loss of afferent input through IHC or the associated type I auditory nerve fibers. The other occurs when the medial olivocochlear efferent neurons lose their cochlear targets, the OHC, and may as compensation increase their synapse numbers in the VCN.

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“…However, this possibility seems rather unlikely due to the following arguments: First, the pattern of spontaneous activity in the MNTB of WT mice (Figure 1) is strikingly similar to the activity of MNTB neurons in rats where it closely resembles the spike pattern of spiral ganglion cells (Tritsch et al, 2010), indicating a faithful transmission of spikes from the auditory nerve to the MNTB even at the young ages examined. Secondly, nicotinic α9 AChR subunits are not expressed in the brain and, within the auditory system, are expressed only in the cochlea (Allen Developing Mouse Brain Atlas; Elgoyhen et al, 1994; Zuo et al, 1999) arguing against altered cholinergic transmission at CN neurons (Brown et al, 1988; Brown and Vetter, 2009; Fujino and Oertel, 2001) in α9 KO mice. Third, glutamate sensitivity and glutamate-elicited spike patterns of MNTB neurons in α9 KO mice were normal (Figure S2), as well as its afferent pathways (Figure 9).…”

Section: Discussionmentioning

confidence: 99%

The Precise Temporal Pattern of Prehearing Spontaneous Activity Is Necessary for Tonotopic Map Refinement

Clause

Sonntag

et al. 2014

Neuron

203

265

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SUMMARY Patterned spontaneous activity is a hallmark of developing sensory systems. In the auditory system, rhythmic bursts of spontaneous activity are generated in cochlear hair cells and propagated along central auditory pathways. The role of these activity patterns in the development of central auditory circuits has remained speculative. Here we demonstrate that blocking efferent cholinergic neurotransmission to developing hair cells in mice that lack the α9 subunit of nicotinic acetylcholine receptors (α9 KO mice) altered the temporal fine-structure of spontaneous activity without changing activity levels. KO mice showed a severe impairment in the functional and structural sharpening of an inhibitory tonotopic map, as evidenced by deficits in synaptic strengthening and silencing of connections and an absence in axonal pruning. These results provide evidence that the precise temporal pattern of spontaneous activity before hearing onset is crucial for the establishment of precise tonotopy, the major organizing principle of central auditory pathways.

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Olivocochlear Neuron Central Anatomy Is Normal in α9 Knockout Mice

Cited by 15 publications

References 45 publications

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

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

Up-regulation of GAP-43 in the chinchilla ventral cochlear nucleus after carboplatin-induced hearing loss: Correlations with inner hair cell loss and outer hair cell loss

The Precise Temporal Pattern of Prehearing Spontaneous Activity Is Necessary for Tonotopic Map Refinement

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