scholarly journals Dendritic HCN Channels Shape Excitatory Postsynaptic Potentials at the Inner Hair Cell Afferent Synapse in the Mammalian Cochlea

2010 ◽  
Vol 103 (5) ◽  
pp. 2532-2543 ◽  
Author(s):  
Eunyoung Yi ◽  
Isabelle Roux ◽  
Elisabeth Glowatzki

Synaptic transmission at the inner hair cell (IHC) afferent synapse, the first synapse in the auditory pathway, is specialized for rapid and reliable signaling. Here we investigated the properties of a hyperpolarization-activated current ( Ih), expressed in the afferent dendrite of auditory nerve fibers, and its role in shaping postsynaptic activity. We used whole cell patch-clamp recordings from afferent dendrites directly where they contact the IHC in excised postnatal rat cochlear turns. Excitatory postsynaptic potentials (EPSPs) of variable amplitude (1–35 mV) were found with 10–90% rise times of about 1 ms and time constants of decay of about 5 ms at room temperature. Current–voltage relations recorded in afferent dendrites revealed Ih. The pharmacological profile and reversal potential (−45 mV) indicated that Ih is mediated by hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels. The HCN channel subunits HCN1, HCN2, and HCN4 were found to be expressed in afferent dendrites using immunolabeling. Raising intracellular cAMP levels sped up the activation kinetics, increased the magnitude of Ih and shifted the half activation voltage ( Vhalf) to more positive values (−104 ± 3 to −91 ± 2 mV). Blocking Ih with 50 μM ZD7288 resulted in hyperpolarization of the resting membrane potential (∼4 mV) and slowing the decay of the EPSP by 47%, suggesting that Ih is active at rest and shortens EPSPs, thereby potentially improving rapid and reliable signaling at this first synapse in the auditory pathway.

1983 ◽  
Vol 91 (4) ◽  
pp. 421-426 ◽  
Author(s):  
Terry J. Garfinkle ◽  
James C. Saunders

The observation that hair cell tuning curves exhibit frequency selectivity as sharply tuned as that seen in auditory nerve fibers has prompted closer examination of the sensory hairs or stereocilia. The present study was designed to examine the morphologic organization of inner hair cell stereocilia in a mammalian species, the neonatal C57BL/6J mouse. The cochleae of mice were fixed in OSO4, dehydrated, dissected, and prepared for scanning electron microscopy. An examination of the number of stereocilia per inner hair cell revealed an orderly decrease from base to apex. Conversely, there was a 300% increase in the height of the tallest stereocilia, a 100% increase in the height of the middle row stereocilia, and a 30% increase in shortest stereocilia from base to apex. The total surface area of the stereocilia, per hair cell, was shown to increase by approximately 250% from the base to the apex of the cochlea.


Neuron ◽  
2001 ◽  
Vol 29 (3) ◽  
pp. 681-690 ◽  
Author(s):  
Dirk Beutner ◽  
Thomas Voets ◽  
Erwin Neher ◽  
Tobias Moser

2021 ◽  
Vol 11 (4) ◽  
pp. 639-652
Author(s):  
Rosamaria Santarelli ◽  
Pietro Scimemi ◽  
Chiara La Morgia ◽  
Elona Cama ◽  
Ignacio del Castillo ◽  
...  

Auditory Neuropathy (AN) is a hearing disorder characterized by disruption of temporal coding of acoustic signals in auditory nerve fibers resulting in the impairment of auditory perceptions that rely on temporal cues. Mutations in several nuclear and mitochondrial genes have been associated to the most well-known forms of AN. Underlying mechanisms include both pre-synaptic and post-synaptic disorders affecting inner hair cell (IHC) depolarization, neurotransmitter release from ribbon synapses, spike initiation in auditory nerve terminals, loss of nerve fibers and impaired conduction, all occurring in the presence of normal physiological measures of outer hair cell (OHC) activities (otoacoustic emissions [OAEs] and cochlear microphonic [CM]). Disordered synchrony of auditory nerve activity has been suggested as the basis of both the profound alterations of auditory brainstem responses (ABRs) and impairment of speech perception. We will review how electrocochleography (ECochG) recordings provide detailed information to help objectively define the sites of auditory neural dysfunction and their effect on inner hair cell receptor summating potential (SP) and compound action potential (CAP), the latter reflecting disorders of ribbon synapses and auditory nerve fibers.


2021 ◽  
Vol 13 ◽  
Author(s):  
Shelby A. Payne ◽  
Matthew S. Joens ◽  
Heather Chung ◽  
Natalie Skigen ◽  
Adam Frank ◽  
...  

Auditory nerve fibers (ANFs) innervating the same inner hair cell (IHC) may have identical frequency tuning but different sound response properties. In cat and guinea pig, ANF response properties correlate with afferent synapse morphology and position on the IHC, suggesting a causal structure-function relationship. In mice, this relationship has not been fully characterized. Here we measured the emergence of synaptic morphological heterogeneities during maturation of the C57BL/6J mouse cochlea by comparing postnatal day 17 (p17, ∼3 days after hearing onset) with p34, when the mouse cochlea is mature. Using serial block face scanning electron microscopy and three-dimensional reconstruction we measured the size, shape, vesicle content, and position of 70 ribbon synapses from the mid-cochlea. Several features matured over late postnatal development. From p17 to p34, presynaptic densities (PDs) and post-synaptic densities (PSDs) became smaller on average (PDs: 0.75 to 0.33; PSDs: 0.58 to 0.31 μm2) and less round as their short axes shortened predominantly on the modiolar side, from 770 to 360 nm. Membrane-associated synaptic vesicles decreased in number from 53 to 30 per synapse from p17 to p34. Anatomical coupling, measured as PSD to ribbon distance, tightened predominantly on the pillar side. Ribbons became less spherical as long-axes lengthened only on the modiolar side of the IHC, from 372 to 541 nm. A decreasing gradient of synaptic ribbon size along the modiolar-pillar axis was detected only at p34 after aligning synapses of adjacent IHCs to a common reference frame (median volumes in nm3 × 106: modiolar 4.87; pillar 2.38). The number of ribbon-associated synaptic vesicles scaled with ribbon size (range 67 to 346 per synapse at p34), thus acquiring a modiolar-pillar gradient at p34, but overall medians were similar at p17 (120) and p34 (127), like ribbon surface area (0.36 vs. 0.34 μm2). PD and PSD morphologies were tightly correlated to each other at individual synapses, more so at p34 than p17, but not to ribbon morphology. These observations suggest that PDs and PSDs mature according to different cues than ribbons, and that ribbon size may be more influenced by cues from the IHC than the surrounding tissue.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pierre Hakizimana ◽  
Anders Fridberger

AbstractMammalian hearing depends on sound-evoked displacements of the stereocilia of inner hair cells (IHCs), which cause the endogenous mechanoelectrical transducer channels to conduct inward currents of cations including Ca2+. Due to their presumed lack of contacts with the overlaying tectorial membrane (TM), the putative stimulation mechanism for these stereocilia is by means of the viscous drag of the surrounding endolymph. However, despite numerous efforts to characterize the TM by electron microscopy and other techniques, the exact IHC stereocilia-TM relationship remains elusive. Here we show that Ca2+-rich filamentous structures, that we call Ca2+ ducts, connect the TM to the IHC stereocilia to enable mechanical stimulation by the TM while also ensuring the stereocilia access to TM Ca2+. Our results call for a reassessment of the stimulation mechanism for the IHC stereocilia and the TM role in hearing.


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