Structure and Function of the Hair Cell Ribbon Synapse

Faithful information transfer at the hair cell afferent synapse requires synaptic transmission to be both reliable and temporally precise. The release of neurotransmitter must exhibit both rapid on and off kinetics to accurately follow acoustic stimuli with a periodicity of 1 ms or less. To ensure such remarkable temporal fidelity, the cochlear hair cell afferent synapse undoubtedly relies on unique cellular and molecular specializations. While the electron microscopy hallmark of the hair cell afferent synapse — the electron-dense synaptic ribbon or synaptic body — has been recognized for decades, dissection of the synapse’s molecular make-up has only just begun. Recent cell physiology studies have added important insights into the synaptic mechanisms underlying fidelity and reliability of sound coding. The presence of the synaptic ribbon links afferent synapses of cochlear and vestibular hair cells to photoreceptors and bipolar neurons of the retina. This review focuses on major advances in understanding the hair cell afferent synapse molecular anatomy and function that have been achieved during the past years

Auditory Cortex Basal Activity Modulates Cochlear Responses in Chinchillas

Background: The auditory efferent system has unique neuroanatomical pathways that connect the cerebral cortex with sensory receptor cells. Pyramidal neurons located in layers V and VI of the primary auditory cortex constitute descending projections to the thalamus, inferior colliculus, and even directly to the superior olivary complex and to the cochlear nucleus. Efferent pathways are connected to the cochlear receptor by the olivocochlear system, which innervates outer hair cells and auditory nerve fibers. The functional role of the cortico-olivocochlear efferent system remains debated. We hypothesized that auditory cortex basal activity modulates cochlear and auditory-nerve afferent responses through the efferent system. Methodology/Principal Findings: Cochlear microphonics (CM), auditory-nerve compound action potentials (CAP) and auditory cortex evoked potentials (ACEP) were recorded in twenty anesthetized chinchillas, before, during and after auditory cortex deactivation by two methods: lidocaine microinjections or cortical cooling with cryoloops. Auditory cortex deactivation induced a transient reduction in ACEP amplitudes in fifteen animals (deactivation experiments) and a permanent reduction in five chinchillas (lesion experiments). We found significant changes in the amplitude of CM in both types of experiments, being the most common effect a CM decrease found in fifteen animals. Concomitantly to CM amplitude changes, we found CAP increases in seven chinchillas and CAP reductions in thirteen animals. Although ACE

Disruption of Lateral Efferent Pathways: Functional Changes in Auditory Evoked Responses

The functional consequences of selectively lesioning the lateral olivocochlear efferent system in guinea pigs were studied. The lateral superior olive (LSO) contains the cell bodies of lateral olivocochlear neurons. Melittin, a cytotoxic chemical, was injected into the brain stem using stereotaxic coordinates and near-field evoked potentials to target the LSO. Brain stem histology revealed discrete damage to the LSO following the injections. Functional consequences of this damage were reflected in depressed amplitude of the compound action potential of the eighth nerve (CAP) following the lesion. Threshold sensitivity and N1 latencies were relatively unchanged. Onset adaptation of the cubic distortion product otoacoustic emission (DPOAE) was evident, suggesting a reasonably intact medial efferent system. The present results provide the first report of functional changes induced by isolated manipulation of the lateral efferent pathway. They also confirm the suggestion that changes in single-unit auditory nerve activity after cutting the olivocochlear bundle are probably a consequence of disrupting the more lateral of the two olivocochlear efferent pathways.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41379/1/10162_2002_Article_3018.pd

Glutamine synthetase and glutamate metabolism in the guinea pig cochlea

Glutamate is thought to act as a neurotransmitter of the sensory hair cells of the organ of Corti. Glutamine synthetase could be involved in a type of glutamate-glutamine cycle in the cochlea which could clear glutamate off the synaptic cleft and replenish the hair cell glutamate neurotransmitter store. Using both light and electron microscopic immunocytochemistry to localize this enzyme in the guinea pig cochlea, we have observed immunoreactive satellite glial cells surrounding parvalbumin-immunoreactive primary auditory neurons in the spiral ganglion. Glutamine synthetase was also detected in Schwann cells of the osseous spiral lamina which form the myelin sheath of nerve fibers. On the contrary, no immunoreactivity could be observed in the cochlear nerve and in the organ of Corti, although this organ contains structures able to take up glutamate. Although they confirm earlier works involving glutamine synthetase in the conversion of l-[ 3H]glutamate taken up by glial cells, our results suggest that the cochlear glutamate-glutamine cycle is not primarily involved in the recycling and replenishment of hair cell neurotransmitter glutamate. Alternatively, it is proposed that glutamine synthetase functions to limit the perilymphatic glutamate concentrations

Mausmutanten mit veränderten afferenten Synapsen der inneren Haarzellen als Tiermodelle der auditorischen Neuropathie

Die perisynaptische Audiopathie (auditorische Neuropathie) ist durch das Vorhandensein von otoakustischen Emissionen bei pathologischen auditorisch evozierten Potentialen gekennzeichnet. Die ursächlichen Pathomechanismen sind noch weitgehend unklar. Es könnte sich sowohl um Störungen des Hörvorganges im Bereich der inneren Haarzellen (IHZ), ihrer afferenten Synapsen oder des Hörnervs handeln . Die Charakterisierung der Pathomechanismen ist durch den Mangel an spezifischen audiologischen Tests, die zwischen Dysfunktionen an den genannten Strukturen unterscheiden könnten, limitiert. Wir untersuchen die Funktion der afferenten Synapse normaler und schwerhöriger Mäuse mit morphologischen sowie zell- und systemphysiologischen Methoden. Die zwei hier vorgestellten Tiermodelle, die Bassoon (synaptisches Protein) Mausmutante und die CaV1.3 (Ca2+ Kanal) Knockout-Maus, zeigen eine hochgradige Schwerhörigkeit bzw. Taubheit. In beiden Fällen liegt eine Dysfunktion der inneren Haarzelle und ihrer Synapsen vor, denen die synaptischen Bänder fehlen. Während in der CaV1.3 KO-Maus Depolarisationen wegen des fehlenden Ca2+-Einstroms auch bei langen Stimuli kaum Exozytose induzierten, beobachteten wir in den Bassoon-Mutanten nur einen selektiven Verlust der schnell freisetzbaren Vesikelpopulation (Readily Releasable Pool, RRP). Dieser Verlust des RRP führte zu einer pantonalen Anhebung der CAP-Schwelle um 50 dB