A gene cadre orchestrates the normal development of sensory and non-sensory cells in the inner ear, segregating the cochlea with a distinct tonotopic sound frequency map, similar brain projection, and five vestibular end-organs. However, the role of genes driving the ear development is largely unknown. Here, we show double deletion of the Iroquois homeobox 3 and 5 transcription factors (Irx3/5 DKO) leads to the fusion of the saccule and the cochlear base. The overlying otoconia and tectorial membranes are absent in the Irx3/5 DKO inner ear, and the primary auditory neurons project fibers to both the saccule and cochlear hair cells. The central neuronal projections from the cochlear apex-base contour are not fully segregated into a dorsal and ventral innervation in the Irx3/5 DKO cochlear nucleus, obliterating the characteristic tonotopic auditory map. Additionally, Irx3/5 deletion reveals a pronounced cochlear-apex-vestibular "vestibular-cochlear" nerve (VCN) bilateral connection that is less noticeable in wild-type control mice. Moreover, the incomplete segregation of apex and base projections that expands fibers to connect with vestibular nuclei. The results suggest the mammalian cochlear apex is a derived lagena reminiscent of sarcopterygians. Thus, Irx3 and 5 are potential evolutionary branch-point genes necessary for balance-sound segregation, which fused into a saccule-cochlea organization.

• MeSH
• Homeodomain Proteins * genetics   metabolism   MeSH
• Cochlea * physiology   MeSH
• Mice, Knockout * MeSH
• Mice MeSH
• Saccule and Utricle * physiology   MeSH
• Auditory Pathways physiology   MeSH
• Transcription Factors * genetics   metabolism   deficiency   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

This review provides an up-to-date source of information on the primary auditory neurons or spiral ganglion neurons in the cochlea. These neurons transmit auditory information in the form of electric signals from sensory hair cells to the first auditory nuclei of the brain stem, the cochlear nuclei. Congenital and acquired neurosensory hearing loss affects millions of people worldwide. An increasing body of evidence suggest that the primary auditory neurons degenerate due to noise exposure and aging more readily than sensory cells, and thus, auditory neurons are a primary target for regenerative therapy. A better understanding of the development and function of these neurons is the ultimate goal for long-term maintenance, regeneration, and stem cell replacement therapy. In this review, we provide an overview of the key molecular factors responsible for the function and neurogenesis of the primary auditory neurons, as well as a brief introduction to stem cell research focused on the replacement and generation of auditory neurons.

• MeSH
• Spiral Ganglion embryology   physiology   MeSH
• Induced Pluripotent Stem Cells cytology   MeSH
• Cochlea embryology   physiology   MeSH
• Humans MeSH
• Brain Stem MeSH
• Mutation MeSH
• Mice MeSH
• Neurogenesis MeSH
• Neurons physiology   MeSH
• Cochlear Nucleus embryology   physiology   MeSH
• Hearing Loss, Sensorineural physiopathology   MeSH
• Regenerative Medicine methods   MeSH
• Base Sequence MeSH
• Evoked Potentials, Auditory, Brain Stem MeSH
• Hair Cells, Auditory physiology   MeSH
• Ear, Inner embryology   physiology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

To examine whether exposure to sodium salicylate disrupts expression of vesicular glutamate transporter 3 (VGLUT3) and whether the alteration in expression corresponds to increased risk for tinnitus. Rats were treated with saline (control) or sodium salicylate (treated) Rats were examined for tinnitus by monitoring gap-pre-pulse inhibition of the acoustic startle reflex (GPIAS). Auditory brainstem response (ABR) was applied to evaluate hearing function after treatment. Rats were sacrificed after injection to obtain the cochlea, cochlear nucleus (CN), and inferior colliculus (IC) for examination of VGLUT3 expression. No significant differences in hearing thresholds between groups were identified (p>0.05). Tinnitus in sodium salicylate-treated rats was confirmed by GPIAS. VGLUT3 encoded by solute carrier family 17 members 8 (SLC17a8) expression was significantly increased in inner hair cells (IHCs) of the cochlea in treated animals, compared with controls (p<0.01). No significant differences in VGLUT3 expression between groups were found for the cochlear nucleus (CN) or IC (p>0.05). Exposure to sodium salicylate may disrupt SLC17a8 expression in IHCs, leading to alterations that correspond to tinnitus in rats. However, the CN and IC are unaffected by exposure to sodium salicylate, suggesting that enhancement of VGLUT3 expression in IHCs may contribute to the pathogenesis of tinnitus.

• MeSH
• Anti-Inflammatory Agents, Non-Steroidal adverse effects   MeSH
• Inferior Colliculi drug effects   metabolism   MeSH
• Cochlear Nucleus drug effects   metabolism   MeSH
• Rats, Wistar MeSH
• Sodium Salicylate adverse effects   MeSH
• Auditory Threshold drug effects   MeSH
• Tinnitus chemically induced   MeSH
• Vesicular Glutamate Transport Proteins metabolism   MeSH
• Hair Cells, Auditory, Inner drug effects   metabolism   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Hearing depends on extracting frequency, intensity, and temporal properties from sound to generate an auditory map for acoustical signal processing. How physiology intersects with molecular specification to fine tune the developing properties of the auditory system that enable these aspects remains unclear. We made a novel conditional deletion model that eliminates the transcription factor NEUROD1 exclusively in the ear. These mice (both sexes) develop a truncated frequency range with no neuroanatomically recognizable mapping of spiral ganglion neurons onto distinct locations in the cochlea nor a cochleotopic map presenting topographically discrete projections to the cochlear nuclei. The disorganized primary cochleotopic map alters tuning properties of the inferior colliculus units, which display abnormal frequency, intensity, and temporal sound coding. At the behavioral level, animals show alterations in the acoustic startle response, consistent with altered neuroanatomical and physiological properties. We demonstrate that absence of the primary afferent topology during embryonic development leads to dysfunctional tonotopy of the auditory system. Such effects have never been investigated in other sensory systems because of the lack of comparable single gene mutation models.SIGNIFICANCE STATEMENT All sensory systems form a topographical map of neuronal projections from peripheral sensory organs to the brain. Neuronal projections in the auditory pathway are cochleotopically organized, providing a tonotopic map of sound frequencies. Primary sensory maps typically arise by molecular cues, requiring physiological refinements. Past work has demonstrated physiologic plasticity in many senses without ever molecularly undoing the specific mapping of an entire primary sensory projection. We genetically manipulated primary auditory neurons to generate a scrambled cochleotopic projection. Eliminating tonotopic representation to auditory nuclei demonstrates the inability of physiological processes to restore a tonotopic presentation of sound in the midbrain. Our data provide the first insights into the limits of physiology-mediated brainstem plasticity during the development of the auditory system.

• MeSH
• Behavior, Animal physiology   MeSH
• Inferior Colliculi anatomy & histology   physiology   MeSH
• Spiral Ganglion cytology   physiology   MeSH
• Brain Mapping MeSH
• Mesencephalon embryology   physiology   MeSH
• Mice, Knockout MeSH
• Mice MeSH
• Cochlear Nucleus anatomy & histology   physiology   MeSH
• Hearing physiology   MeSH
• Auditory Perception genetics   physiology   MeSH
• Pregnancy MeSH
• Basic Helix-Loop-Helix Transcription Factors genetics   physiology   MeSH
• Reflex, Startle genetics   physiology   MeSH
• Vestibule, Labyrinth anatomy & histology   physiology   MeSH
• Pitch Perception physiology   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Pregnancy MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH

Inhibitory circuits in the auditory brainstem undergo multiple postnatal changes that are both activity-dependent and activity-independent. We tested to see if the shift from GABA- to glycinergic transmission, which occurs in the rat medial nucleus of the trapezoid body (MNTB) around the onset of hearing, depends on sound-evoked neuronal activity. We prevented the activity by bilateral cochlear ablations in early postnatal rats and studied ionotropic GABA and glycine receptors in MNTB neurons after hearing onset. The removal of the cochlea decreased responses of GABAA and glycine receptors to exogenous agonists as well as the amplitudes of inhibitory postsynaptic currents. The reduction was accompanied by a decrease in the number of glycine receptor- or vesicular GABA transporter-immunopositive puncta. Furthermore, the ablations markedly affected the switch in presynaptic GABAA to glycine receptors. The increase in the expression of postsynaptic glycine receptors and the shift in inhibitory transmitters were not prevented. The results suggest that inhibitory transmission in the MNTB is subject to multiple developmental signals and support the idea that auditory experience plays a role in the maturation of the brainstem glycinergic circuits.

• MeSH
• Ablation Techniques * MeSH
• GABA-A Receptor Agonists pharmacology   MeSH
• Trapezoid Body physiology   MeSH
• Inhibitory Postsynaptic Potentials physiology   MeSH
• Cochlea physiopathology   surgery   MeSH
• Rats MeSH
• Synaptic Transmission * MeSH
• Neural Inhibition drug effects   physiology   MeSH
• Animals, Newborn MeSH
• Receptors, GABA-A physiology   MeSH
• Receptors, Glycine agonists   metabolism   physiology   MeSH
• Evoked Potentials, Auditory, Brain Stem physiology   MeSH
• Vesicular Inhibitory Amino Acid Transport Proteins metabolism   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

RATIONALE: Cochlear implantation is the most effective method of rehabilitation for patients with severe to profound sensorineural hearing loss. Binaural hearing forms the basis of the development of hearing-associated cortical networks in infants and toddlers, but simultaneous bilateral implantation is often postponed due to the demands of classical surgical methods, which are associated with large incisions and a deep bony well. OBJECTIVE: The authors report on the use of a modern, thin implant type and the possibilities it provided to simplify the surgical technique. METHODS AND RESULTS: Recent models of the Cochlear™ Nucleus® implant family were studied in an international retrospective multi-center study: 6 otolaryngologists in 5 centers shared their experiences on 73 consecutively implanted, thin implants. The surgical incision could be made shorter than before and only shallow bony wells or none at all were created in 4 out of 5 centers. No complications occurred. DISCUSSION: This study underlines that implants with thin electronics capsules enable a simplified, fast and safe implantation procedure that allows simultaneous bilateral cochlear implantation.

• MeSH
• Electronics * MeSH
• Internationality * MeSH
• Cochlear Implantation MeSH
• Cochlear Implants * MeSH
• Humans MeSH
• Surveys and Questionnaires MeSH
• Retrospective Studies MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

Tone at moderate levels presented to young rats at a stage (postnatal week-4) presumably that has passed the cortical critical period still can enlarge neurons in the auditory cortex. It remains unclear whether this delayed plastic change occurs only in the cortex, or reflects a change taking place in the auditory brainstem. Here we compared sound-exposure effects on neuronal size in the auditory cortex and the midbrain. Starting from postnatal day 22, young rats were exposed to a low-frequency tone (4 kHz at 65 dB SPL) for a period of 3 (postnatal day 22-25) or 7 (postnatal day 22-29) days before sacrifice. Neurons were analyzed morphometrically from 7 μm-thick histological sections. A marked increase in neuronal size (32%) was found at the cortex in the high-frequency region distant from the exposing tone. The increase in the midbrain was even larger (67%) and was found in both the low and high frequency regions. While cell enlargements were clear at day 29, only in the high frequency region of the cortex a slight enlargement was found at day 22, suggesting that the cortical and subcortical changes are synchronized, if not slightly preceded by the cortex. In contrast, no changes in neuronal size were found in the cochlear nucleus or the visual midbrain. Such differential effects of sound-exposure at the auditory centers across cortical and subcortical levels cannot be explained by a simple activity-driven change occurring earlier in the brainstem, and might involve function of other structures as for example the descending auditory system.

• MeSH
• Acoustic Stimulation MeSH
• Time Factors MeSH
• Bone and Bones MeSH
• Rats MeSH
• Mesencephalon physiology   MeSH
• Brain Stem physiology   MeSH
• Neurons metabolism   physiology   MeSH
• Neuronal Plasticity MeSH
• Cochlear Nucleus metabolism   MeSH
• Rats, Sprague-Dawley MeSH
• Hearing MeSH
• Auditory Pathways physiology   MeSH
• Auditory Cortex physiology   MeSH
• Animals MeSH
• Sound * MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Monografie se zabývá mezi odborníky velmi diskutovaným tématem týkajícím se současné situace v oblasti kochleárních implantací u dětí s těžkým sluchovým postižením. Především sleduje možnosti vzdělávání těchto dětí v ČR a tyto údaje doplňujeo popis téže situace v dalších třech vybraných zemích : Velké Británii, Austrálii a USA. Obsah publikace je rozčleněn do pěti samostatných kapitol, které s tématem úzce souvisejí. Každá kapitola je doplněna výzkumnými údaji konkrétně ilustrujícími popisovanou problematiku. Mimo jiné je sledována efektivita kochleárního implantátu z pohledu předem stanovených faktorů (věk při implantaci, délka trvání hluchoty, rodinné prostředí, eventuální výskyt souběžného postižení v podobě vývojové dysfázie či dyslálie), z pohledu možnosti rozvoje komunikačních kompetencí u jedinců s kochleárním implantátem, a dále pak korelaci mezi rozvojem těchto kompetencí a možnostmi začlenění těchto jedinců do škol hlavního vzdělávacího proudu. Nakladatelská anotace. Kráceno; Publikace představuje aktuální poznatky z oblasti problematiky sluchového postižení a kochleárních implantací spolu s výsledky výzkumné činnosti autorky z let 1996 - 2010.

• MeSH
• Cochlear Implants MeSH
• Persons with Hearing Disabilities MeSH
• Education, Special MeSH
• Education of Persons with Hearing Disabilities MeSH
• Publication type
• Monograph MeSH

• Conspectus
• Výchova a vzdělávání zvláštních skupin osob
• NML Fields
• zdravotně postižení
• pedagogika

SMI-32 antibody recognizes a non-phosphorylated epitope of neurofilament proteins, which are thought to be necessary for the maintenance of large neurons with highly myelinated processes. We investigated the distribution and quantity of SMI-32-immunoreactive(-ir) neurons in individual parts of the rat auditory system. SMI-32-ir neurons were present in all auditory structures; however, in most regions they constituted only a minority of all neurons (10-30%). In the cochlear nuclei, a higher occurrence of SMI-32-ir neurons was found in the ventral cochlear nucleus. Within the superior olivary complex, SMI-32-ir cells were particularly abundant in the medial nucleus of the trapezoid body (MNTB), the only auditory region where SMI-32-ir neurons constituted an absolute majority of all neurons. In the inferior colliculus, a region with the highest total number of neurons among the rat auditory subcortical structures, the percentage of SMI-32-ir cells was, in contrast to the MNTB, very low. In the medial geniculate body, SMI-32-ir neurons were prevalent in the ventral division. At the cortical level, SMI-32-ir neurons were found mainly in layers III, V and VI. Within the auditory cortex, it was possible to distinguish the Te1, Te2 and Te3 areas on the basis of the variable numerical density and volumes of SMI-32-ir neurons, especially when the pyramidal cells of layer V were taken into account. SMI-32-ir neurons apparently form a representative subpopulation of neurons in all parts of the rat central auditory system and may belong to both the inhibitory and excitatory systems, depending on the particular brain region.

• MeSH
• Analysis of Variance MeSH
• Inferior Colliculi cytology   metabolism   MeSH
• Immunohistochemistry MeSH
• Rats MeSH
• Geniculate Bodies cytology   metabolism   MeSH
• Microscopy MeSH
• Antibodies, Monoclonal metabolism   MeSH
• Neurofilament Proteins metabolism   MeSH
• Neurons, Afferent metabolism   MeSH
• Cochlear Nucleus cytology   metabolism   MeSH
• Rats, Long-Evans MeSH
• Prosencephalon cytology   metabolism   MeSH
• Auditory Pathways cytology   MeSH
• Auditory Cortex cytology   metabolism   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

The properties of glycine receptors (GlyRs) depend upon their subunit composition. While the prevalent adult forms of GlyRs are heteromers, previous reports suggested functional α homomeric receptors in mature nervous tissues. Here we show two functionally different GlyRs populations in the rat medial nucleus of trapezoid body (MNTB). Postsynaptic receptors formed α1/β-containing clusters on somatodendritic domains of MNTB principal neurons, colocalizing with glycinergic nerve endings to mediate fast, phasic IPSCs. In contrast, presynaptic receptors on glutamatergic calyx of Held terminals were composed of dispersed, homomeric α1 receptors. Interestingly, the parent cell bodies of the calyces of Held, the globular bushy cells of the cochlear nucleus, expressed somatodendritic receptors (α1/β heteromers) and showed similar clustering and pharmacological profile as GlyRs on MNTB principal cells. These results suggest that specific targeting of GlyR β-subunit produces segregation of GlyR subtypes involved in two different mechanisms of modulation of synaptic strength.

• MeSH
• Dendritic Spines physiology   MeSH
• Electric Stimulation MeSH
• Electrophysiological Phenomena MeSH
• Excitatory Postsynaptic Potentials drug effects   MeSH
• Glycine physiology   MeSH
• Glycine Agents pharmacology   MeSH
• Microscopy, Immunoelectron MeSH
• Immunohistochemistry MeSH
• Kinetics MeSH
• Rats MeSH
• Patch-Clamp Techniques MeSH
• Nerve Endings metabolism   MeSH
• Rats, Wistar MeSH
• Receptors, Glycine drug effects   metabolism   MeSH
• Receptors, Presynaptic metabolism   MeSH
• Auditory Pathways metabolism   MeSH
• Synapses metabolism   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH