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Gary D Housley - One of the best experts on this subject based on the ideXlab platform.

  • type ii Spiral Ganglion afferent neurons drive medial olivocochlear reflex suppression of the cochlear amplifier
    Nature Communications, 2015
    Co-Authors: Kristina E Froud, Allen F Ryan, Jennie Me Cederholm, Ann Chi Yan Wong, Matthias Klugmann, Shaun L Sandow, Jeanpierre Julien, Gary D Housley
    Abstract:

    The medial olivocochlear efferent reflex regulates cochlear outer hair cell-based amplification of sound energy. Here the authors show this dynamic control of hearing sensitivity is driven by sensory input from the outer hair cells and their type II Spiral Ganglion neuron innervation.

  • Neural Cell Adhesion Molecule L1 Modulates Type I But Not Type II Inner Ear Spiral Ganglion Neurite Outgrowth in an In Vitro Alternate Choice Assay
    Journal of Molecular Neuroscience, 2013
    Co-Authors: Yves Brand, Daniel Bodmer, Gary D Housley, Michael Sung, Eduardo Chavez, Allen F Ryan
    Abstract:

    L1, a neural cell adhesion molecule of the immunoglobulin superfamily, is widely expressed in the nervous system and important in axonal outgrowth, guidance, synapse formation, and signaling. Gene deletion studies emphasize the significance of L1 during development of the central nervous system and L1 is crucial for the topographic targeting of retinal axons. In contrast to the brain and retina, the role of L1 in the inner ear is largely unknown. While previous studies have localized L1 in the developing inner ear of the chicken and mouse, its function during the innervation of the cochlea still remains largely unclear. We therefore investigated the functional role of L1 in the mammalian inner ear. Our aim was to determine whether or not L1 can modulate type I and/or type II Spiral Ganglion neuron outgrowth using an in vitro alternate choice assay. We found that L1, presented in stripe micropatterns, provide directional cues to neonatal rodent type I but not type II inner ear Spiral Ganglion neurites. The results suggest that L1 may play a role in axonal pathfinding of type I Spiral Ganglion dendrites toward their inner hair cell targets but not of type II toward the outer hair cells.

  • type i vs type ii Spiral Ganglion neurons exhibit differential survival and neuritogenesis during cochlear development
    Neural Development, 2011
    Co-Authors: Meagan Barclay, Allen F Ryan, Gary D Housley
    Abstract:

    The mechanisms that consolidate neural circuitry are a major focus of neuroscience. In the mammalian cochlea, the refinement of Spiral Ganglion neuron (SGN) innervation to the inner hair cells (by type I SGNs) and the outer hair cells (by type II SGNs) is accompanied by a 25% loss of SGNs. We investigated the segregation of neuronal loss in the mouse cochlea using β-tubulin and peripherin antisera to immunolabel all SGNs and selectively type II SGNs, respectively, and discovered that it is the type II SGN population that is predominately lost within the first postnatal week. Developmental neuronal loss has been attributed to the decline in neurotrophin expression by the target hair cells during this period, so we next examined survival of SGN sub-populations using tissue culture of the mid apex-mid turn region of neonatal mouse cochleae. In organotypic culture for 48 hours from postnatal day 1, endogenous trophic support from the organ of Corti proved sufficient to maintain all type II SGNs; however, a large proportion of type I SGNs were lost. Culture of the Spiral Ganglion as an explant, with removal of the organ of Corti, led to loss of the majority of both SGN sub-types. Brain-derived neurotrophic factor (BDNF) added as a supplement to the media rescued a significant proportion of the SGNs, particularly the type II SGNs, which also showed increased neuritogenesis. The known decline in BDNF production by the rodent sensory epithelium after birth is therefore a likely mediator of type II neuron apoptosis. Our study thus indicates that BDNF supply from the organ of Corti supports consolidation of type II innervation in the neonatal mouse cochlea. In contrast, type I SGNs likely rely on additional sources for trophic support.

  • type iii intermediate filament peripherin inhibits neuritogenesis in type ii Spiral Ganglion neurons in vitro
    Neuroscience Letters, 2010
    Co-Authors: Meagan Barclay, Allen F Ryan, Jeanpierre Julien, Gary D Housley
    Abstract:

    Peripherin, a type III intermediate filament protein, forms part of the cytoskeleton in a subset of neurons, most of which have peripheral fibre projections. Studies suggest a role for peripherin in axon outgrowth and regeneration, but evidence for this in sensory and brain tissues is limited. The exclusive expression of peripherin in a sub-population of primary auditory neurons, the type II Spiral Ganglion neurons (SGN) prompted our investigation of the effect of peripherin gene deletion (pphKO) on these neurons. We used confocal immunofluorescence to examine the establishment of the innervation of the cochlear outer hair cells by the type II SGN neurites in vivo and in vitro, in wildtype (WT) and pphKO mice, in the first postnatal week. The distribution of the type II SGN nerve fibres was normal in pphKO cochleae. However, using P1 Spiral Ganglion explants under culture conditions where the majority of neurites were derived from type II SGN, pphKO resulted in increased numbers of neurites/explant compared to WT controls. Type II SGN neurites from pphKO explants extended ∼double the distance of WT neurites, and had reduced complexity based on greater distance between turning points. Addition of brain-derived neurotrophic factor (BDNF) to the culture media increased neurite number in WT and KO explants ∼30-fold, but did not affect neurite length or distance between turning. These results indicate that peripherin may interact with other cytoskeletal elements to regulate outgrowth of the peripheral neurites of type II SGN, distinguishing these neurons from the type I SGN innervating the inner hair cells.

Allen F Ryan - One of the best experts on this subject based on the ideXlab platform.

  • type ii Spiral Ganglion afferent neurons drive medial olivocochlear reflex suppression of the cochlear amplifier
    Nature Communications, 2015
    Co-Authors: Kristina E Froud, Allen F Ryan, Jennie Me Cederholm, Ann Chi Yan Wong, Matthias Klugmann, Shaun L Sandow, Jeanpierre Julien, Gary D Housley
    Abstract:

    The medial olivocochlear efferent reflex regulates cochlear outer hair cell-based amplification of sound energy. Here the authors show this dynamic control of hearing sensitivity is driven by sensory input from the outer hair cells and their type II Spiral Ganglion neuron innervation.

  • Neural Cell Adhesion Molecule NrCAM Is Expressed in the Mammalian Inner Ear and Modulates Spiral Ganglion Neurite Outgrowth in an In Vitro Alternate Choice Assay
    Journal of Molecular Neuroscience, 2015
    Co-Authors: Yves Brand, Vesna Radojevic, Daniel Bodmer, Michael Sung, Eduardo Chavez, Allen F Ryan
    Abstract:

    Neuron-glial-related cell adhesion molecule (NrCAM) is a neuronal cell adhesion molecule involved in neuron–neuron and neuron–glial adhesion as well as directional signaling during axonal cone growth. NrCAM has been shown to be involved in several cellular processes in the central and peripheral nervous systems, including neurite outgrowth, axonal pathfinding and myelination, fasciculation of nerve fibers, and cell migration. This includes sensory systems such as the eye and olfactory system. However, there are no reports on the expression/function of NrCAM in the auditory system. The aim of the present study was to elucidate the occurrence of NrCAM in the mammalian cochlea and its role in innervation of the auditory end organ. Our work indicates that NrCAM is highly expressed in the developing mammalian cochlea (position consistent with innervation). Moreover, we found that NrCAM, presented in stripe micropatterns, provide directional cues to neonatal rat inner ear Spiral Ganglion neurites in vitro. Our results are consistent with a role for NrCAM in the pathfinding of Spiral Ganglion dendrites toward their hair cell targets in the sensory epithelium.

  • Neural Cell Adhesion Molecule L1 Modulates Type I But Not Type II Inner Ear Spiral Ganglion Neurite Outgrowth in an In Vitro Alternate Choice Assay
    Journal of Molecular Neuroscience, 2013
    Co-Authors: Yves Brand, Daniel Bodmer, Gary D Housley, Michael Sung, Eduardo Chavez, Allen F Ryan
    Abstract:

    L1, a neural cell adhesion molecule of the immunoglobulin superfamily, is widely expressed in the nervous system and important in axonal outgrowth, guidance, synapse formation, and signaling. Gene deletion studies emphasize the significance of L1 during development of the central nervous system and L1 is crucial for the topographic targeting of retinal axons. In contrast to the brain and retina, the role of L1 in the inner ear is largely unknown. While previous studies have localized L1 in the developing inner ear of the chicken and mouse, its function during the innervation of the cochlea still remains largely unclear. We therefore investigated the functional role of L1 in the mammalian inner ear. Our aim was to determine whether or not L1 can modulate type I and/or type II Spiral Ganglion neuron outgrowth using an in vitro alternate choice assay. We found that L1, presented in stripe micropatterns, provide directional cues to neonatal rodent type I but not type II inner ear Spiral Ganglion neurites. The results suggest that L1 may play a role in axonal pathfinding of type I Spiral Ganglion dendrites toward their inner hair cell targets but not of type II toward the outer hair cells.

  • glial cell line derived neurotrophic factor gdnf induces neuritogenesis in the cochlear Spiral Ganglion via neural cell adhesion molecule ncam
    Molecular and Cellular Neuroscience, 2013
    Co-Authors: Sara Euteneuer, Eduardo Chavez, Kuo H Yang, Anke Leichtle, Gabriele Loers, Adel Olshansky, Kwang Pak, Melitta Schachner, Allen F Ryan
    Abstract:

    Glial cell line-derived neurotrophic factor (GDNF) increases survival and neurite extension of Spiral Ganglion neurons (SGNs), the primary neurons of the auditory system, via yet unknown signaling mechanisms. In other cell types, signaling is achieved by the GPI-linked GDNF family receptor α1 (GFRα1) via recruitment of transmembrane receptors: Ret (re-arranged during transformation) and/or NCAM (neural cell adhesion molecule). Here we show that GDNF enhances neuritogenesis in organotypic cultures of Spiral ganglia from 5-day-old rats and mice. Addition of GFRα1-Fc increases this effect. GDNF/GFRα1-Fc stimulation activates intracellular PI3K/Akt and MEK/Erk signaling cascades as detected by Western blot analysis of cultures prepared from rats at postnatal days 5 (P5, before the onset of hearing) and 20 (P20, after the onset of hearing). Both cascades mediate GDNF stimulation of neuritogenesis, since application of the Akt inhibitor Wortmannin or the Erk inhibitor U0126 abolished GDNF/GFRα1-Fc stimulated neuritogenesis in P5 rats. Since cultures of P5 NCAM-deficient mice failed to respond by neuritogenesis to GDNF/GFRα1-Fc, we conclude that NCAM serves as a receptor for GDNF signaling responsible for neuritogenesis in early postnatal Spiral Ganglion.

  • type i vs type ii Spiral Ganglion neurons exhibit differential survival and neuritogenesis during cochlear development
    Neural Development, 2011
    Co-Authors: Meagan Barclay, Allen F Ryan, Gary D Housley
    Abstract:

    The mechanisms that consolidate neural circuitry are a major focus of neuroscience. In the mammalian cochlea, the refinement of Spiral Ganglion neuron (SGN) innervation to the inner hair cells (by type I SGNs) and the outer hair cells (by type II SGNs) is accompanied by a 25% loss of SGNs. We investigated the segregation of neuronal loss in the mouse cochlea using β-tubulin and peripherin antisera to immunolabel all SGNs and selectively type II SGNs, respectively, and discovered that it is the type II SGN population that is predominately lost within the first postnatal week. Developmental neuronal loss has been attributed to the decline in neurotrophin expression by the target hair cells during this period, so we next examined survival of SGN sub-populations using tissue culture of the mid apex-mid turn region of neonatal mouse cochleae. In organotypic culture for 48 hours from postnatal day 1, endogenous trophic support from the organ of Corti proved sufficient to maintain all type II SGNs; however, a large proportion of type I SGNs were lost. Culture of the Spiral Ganglion as an explant, with removal of the organ of Corti, led to loss of the majority of both SGN sub-types. Brain-derived neurotrophic factor (BDNF) added as a supplement to the media rescued a significant proportion of the SGNs, particularly the type II SGNs, which also showed increased neuritogenesis. The known decline in BDNF production by the rodent sensory epithelium after birth is therefore a likely mediator of type II neuron apoptosis. Our study thus indicates that BDNF supply from the organ of Corti supports consolidation of type II innervation in the neonatal mouse cochlea. In contrast, type I SGNs likely rely on additional sources for trophic support.

Jianxin Bao - One of the best experts on this subject based on the ideXlab platform.

  • Author's personal copy Anti-epileptic drugs delay age-related loss of Spiral Ganglion neurons via T-type calcium channel
    2020
    Co-Authors: Debin Lei, Kevin K Ohlemiller, Xia Gao, Philip Perez, Chienchang Chen, Kevin P Campbell, Aizhen Yang Hood, Jianxin Bao
    Abstract:

    a b s t r a c t Loss of Spiral Ganglion neurons is a major cause of age-related hearing loss (presbycusis). Despite being the third most prevalent condition afflicting elderly persons, there are no known medications to prevent presbycusis. Because calcium signaling has long been implicated in age-related neuronal death, we investigated T-type calcium channels. This family is comprised of three members (Ca v 3.1, Ca v 3.2, and Ca v 3.3), based on their respective main pore-forming alpha subunits: a1G, a1H, and a1I. In the present study, we report a significant delay of age-related loss of cochlear function and preservation of Spiral Ganglion neurons in a1H null and heterozygous mice, clearly demonstrating an important role for Ca v 3.2 in age-related neuronal loss. Furthermore, we show that anticonvulsant drugs from a family of T-type calcium channel blockers can significantly preserve Spiral Ganglion neurons during aging. To our knowledge, this is the first report of drugs capable of diminishing age-related loss of Spiral Ganglion neurons

  • anti epileptic drugs delay age related loss of Spiral Ganglion neurons via t type calcium channel
    Hearing Research, 2011
    Co-Authors: Debin Lei, Kevin K Ohlemiller, Xia Gao, Philip Perez, Chienchang Chen, Kevin P Campbell, Aizhen Yang Hood, Jianxin Bao
    Abstract:

    Loss of Spiral Ganglion neurons is a major cause of age-related hearing loss (presbycusis). Despite being the third most prevalent condition afflicting elderly persons, there are no known medications to prevent presbycusis. Because calcium signaling has long been implicated in age-related neuronal death, we investigated T-type calcium channels. This family is comprised of three members (Ca(v)3.1, Ca(v)3.2, and Ca(v)3.3), based on their respective main pore-forming alpha subunits: α1G, α1H, and α1I. In the present study, we report a significant delay of age-related loss of cochlear function and preservation of Spiral Ganglion neurons in α1H null and heterozygous mice, clearly demonstrating an important role for Ca(v)3.2 in age-related neuronal loss. Furthermore, we show that anticonvulsant drugs from a family of T-type calcium channel blockers can significantly preserve Spiral Ganglion neurons during aging. To our knowledge, this is the first report of drugs capable of diminishing age-related loss of Spiral Ganglion neurons.

  • age related loss of Spiral Ganglion neurons
    Hearing Research, 2010
    Co-Authors: Jianxin Bao, Kevin K Ohlemiller
    Abstract:

    Spiral Ganglion neurons (SGNs) are the relay station for auditory information between hair cells and central nervous system. Age-related decline of auditory function due to SGN loss can not be ameliorated by hearing aids or cochlear implants. Recent findings clearly indicate that survival of SGNs during aging depends on genetic and environmental interactions, which can be demonstrated at the systemic, tissue, cellular, and molecular levels. At the systemic level, both insulin/insulin-like growth factor-1 and lipophilic/steroid hormone pathways influence SGN survival during aging. At the level of organ of the Corti, it is difficult to determine whether age-related SGN loss is primary or secondary degeneration. However, a late stage of SGN degeneration may be independent of age-related loss of hair cells. At the cellular and molecular level, several pathways, particularly free radical and calcium signaling pathways, can influence age-related SGN loss, and further studies should determine how these pathways contribute to SGN loss, such as whether they directly or indirectly act on SGNs. With the advancement of recent genetic and pharmacologic tools, we should not only understand how SGNs die during aging, but also find ways to delay this loss.

Kevin K Ohlemiller - One of the best experts on this subject based on the ideXlab platform.

  • Author's personal copy Anti-epileptic drugs delay age-related loss of Spiral Ganglion neurons via T-type calcium channel
    2020
    Co-Authors: Debin Lei, Kevin K Ohlemiller, Xia Gao, Philip Perez, Chienchang Chen, Kevin P Campbell, Aizhen Yang Hood, Jianxin Bao
    Abstract:

    a b s t r a c t Loss of Spiral Ganglion neurons is a major cause of age-related hearing loss (presbycusis). Despite being the third most prevalent condition afflicting elderly persons, there are no known medications to prevent presbycusis. Because calcium signaling has long been implicated in age-related neuronal death, we investigated T-type calcium channels. This family is comprised of three members (Ca v 3.1, Ca v 3.2, and Ca v 3.3), based on their respective main pore-forming alpha subunits: a1G, a1H, and a1I. In the present study, we report a significant delay of age-related loss of cochlear function and preservation of Spiral Ganglion neurons in a1H null and heterozygous mice, clearly demonstrating an important role for Ca v 3.2 in age-related neuronal loss. Furthermore, we show that anticonvulsant drugs from a family of T-type calcium channel blockers can significantly preserve Spiral Ganglion neurons during aging. To our knowledge, this is the first report of drugs capable of diminishing age-related loss of Spiral Ganglion neurons

  • fractalkine signaling regulates macrophage recruitment into the cochlea and promotes the survival of Spiral Ganglion neurons after selective hair cell lesion
    The Journal of Neuroscience, 2015
    Co-Authors: Tejbeer Kaur, Darius Zamani, Ling Tong, Edwin W Rubel, Kevin K Ohlemiller, Keiko Hirose, Mark E Warchol
    Abstract:

    Macrophages are recruited into the cochlea in response to injury caused by acoustic trauma or ototoxicity, but the nature of the interaction between macrophages and the sensory structures of the inner ear remains unclear. The present study examined the role of fractalkine signaling in regulating the injury-evoked behavior of macrophages following the selective ablation of cochlear hair cells. We used a novel transgenic mouse model in which the human diphtheria toxin receptor (huDTR) is selectively expressed under the control of Pou4f3 , a hair cell-specific transcription factor. Administration of diphtheria toxin (DT) to these mice resulted in nearly complete ablation of cochlear hair cells, with no evident pathology among supporting cells, Spiral Ganglion neurons, or cells of the cochlear lateral wall. Hair cell death led to an increase in macrophages associated with the sensory epithelium of the cochlea. Their numbers peaked at 14 days after DT and then declined at later survival times. Increased macrophages were also observed within the Spiral Ganglion, but their numbers remained elevated for (at least) 56 d after DT. To investigate the role of fractalkine signaling in macrophage recruitment, we crossed huDTR mice to a mouse line that lacks expression of the fractalkine receptor (CX 3 CR1). Disruption of fractalkine signaling reduced macrophage recruitment into both the sensory epithelium and Spiral Ganglion and also resulted in diminished survival of Spiral Ganglion neurons after hair cell death. Our results suggest a fractalkine-mediated interaction between macrophages and the neurons of the cochlea. SIGNIFICANCE STATEMENT It is known that damage to the inner ear leads to recruitment of inflammatory cells (macrophages), but the chemical signals that initiate this recruitment and the functions of macrophages in the damaged ear are unclear. Here we show that fractalkine signaling regulates macrophage recruitment into the cochlea and also promotes the survival of cochlear afferents after selective hair cell lesion. Because these afferent neurons carry sound information from the cochlea to the auditory brainstem, their survival is a key determinant of the success of cochlear prosthetics. Our data suggest that fractalkine signaling in the cochlea is neuroprotective, and reveal a previously uncharacterized interaction between cells of the cochlea and the innate immune system.

  • anti epileptic drugs delay age related loss of Spiral Ganglion neurons via t type calcium channel
    Hearing Research, 2011
    Co-Authors: Debin Lei, Kevin K Ohlemiller, Xia Gao, Philip Perez, Chienchang Chen, Kevin P Campbell, Aizhen Yang Hood, Jianxin Bao
    Abstract:

    Loss of Spiral Ganglion neurons is a major cause of age-related hearing loss (presbycusis). Despite being the third most prevalent condition afflicting elderly persons, there are no known medications to prevent presbycusis. Because calcium signaling has long been implicated in age-related neuronal death, we investigated T-type calcium channels. This family is comprised of three members (Ca(v)3.1, Ca(v)3.2, and Ca(v)3.3), based on their respective main pore-forming alpha subunits: α1G, α1H, and α1I. In the present study, we report a significant delay of age-related loss of cochlear function and preservation of Spiral Ganglion neurons in α1H null and heterozygous mice, clearly demonstrating an important role for Ca(v)3.2 in age-related neuronal loss. Furthermore, we show that anticonvulsant drugs from a family of T-type calcium channel blockers can significantly preserve Spiral Ganglion neurons during aging. To our knowledge, this is the first report of drugs capable of diminishing age-related loss of Spiral Ganglion neurons.

  • age related loss of Spiral Ganglion neurons
    Hearing Research, 2010
    Co-Authors: Jianxin Bao, Kevin K Ohlemiller
    Abstract:

    Spiral Ganglion neurons (SGNs) are the relay station for auditory information between hair cells and central nervous system. Age-related decline of auditory function due to SGN loss can not be ameliorated by hearing aids or cochlear implants. Recent findings clearly indicate that survival of SGNs during aging depends on genetic and environmental interactions, which can be demonstrated at the systemic, tissue, cellular, and molecular levels. At the systemic level, both insulin/insulin-like growth factor-1 and lipophilic/steroid hormone pathways influence SGN survival during aging. At the level of organ of the Corti, it is difficult to determine whether age-related SGN loss is primary or secondary degeneration. However, a late stage of SGN degeneration may be independent of age-related loss of hair cells. At the cellular and molecular level, several pathways, particularly free radical and calcium signaling pathways, can influence age-related SGN loss, and further studies should determine how these pathways contribute to SGN loss, such as whether they directly or indirectly act on SGNs. With the advancement of recent genetic and pharmacologic tools, we should not only understand how SGNs die during aging, but also find ways to delay this loss.

Robin L. Davis - One of the best experts on this subject based on the ideXlab platform.

  • I _h and HCN Channels in Murine Spiral Ganglion Neurons: Tonotopic Variation, Local Heterogeneity, and Kinetic Model
    Journal of the Association for Research in Otolaryngology, 2014
    Co-Authors: Qing Liu, Paul B. Manis, Robin L. Davis
    Abstract:

    One of the major contributors to the response profile of neurons in the auditory pathways is the I _h current. Its properties such as magnitude, activation, and kinetics not only vary among different types of neurons (Banks et al., J Neurophysiol 70:1420–1432, 1993 ; Fu et al., J Neurophysiol 78:2235–2245, 1997 ; Bal and Oertel, J Neurophysiol 84:806–817, 2000 ; Cao and Oertel, J Neurophysiol 94:821–832, 2005 ; Rodrigues and Oertel, J Neurophysiol 95:76–87, 2006 ; Yi et al., J Neurophysiol 103:2532–2543, 2010 ), but they also display notable diversity in a single population of Spiral Ganglion neurons (Mo and Davis, J Neurophysiol 78:3019–3027, 1997 ), the first neural element in the auditory periphery. In this study, we found from somatic recordings that part of the heterogeneity can be attributed to variation along the tonotopic axis because I _h in the apical neurons have more positive half-activation voltage levels than basal neurons. Even within a single cochlear region, however, I _h current properties are not uniform. To account for this heterogeneity, we provide immunocytochemical evidence for variance in the intracellular density of the hyperpolarization-activated cyclic nucleotide-gated channel α-subunit 1 (HCN1), which mediates I _h current. We also observed different combinations of HCN1 and HCN4 α-subunits from cell to cell. Lastly, based on the physiological data, we performed kinetic analysis for the I _h current and generated a mathematical model to better understand varied I _h on Spiral Ganglion function. Regardless of whether I _h currents are recorded at the nerve terminals (Yi et al., J Neurophysiol 103:2532-2543, 2010 ) or at the somata of Spiral Ganglion neurons, they have comparable mean half-activation voltage and induce similar resting membrane potential changes, and thus our model may also provide insights into the impact of I _h on synaptic physiology.

  • heterogeneous intrinsic excitability of murine Spiral Ganglion neurons is determined by kv1 and hcn channels
    Neuroscience, 2014
    Co-Authors: Qing Liu, Edmund Lee, Robin L. Davis
    Abstract:

    The Spiral Ganglion conveys afferent auditory information predominantly through a single class of type I neurons that receive signals from inner hair cell sensory receptors. These auditory primary afferents, like in other systems (Puopolo and Belluzzi, 1998; Gascon and Moqrich, 2010; Leao et al., 2012) possess a marked diversity in their electrophysiological features (Taberner and Liberman, 2005). Consistent with these observations, when the auditory primary afferents were assessed in neuronal explants separated from their peripheral and central targets it was found that individual neurons were markedly heterogeneous in their endogenous electrophysiological features. One aspect of this heterogeneity, obvious throughout the Ganglion, was their wide range of excitability as assessed by voltage threshold measurements (Liu and Davis, 2007). Thus, while neurons in the base differed significantly from apical and middle neurons in their voltage thresholds, each region showed distinctly wide ranges of values. To determine whether the resting membrane potentials (RMPs) of these neurons correlate with the threshold distribution and to identify the ion channel regulatory elements underlying heterogeneous neuronal excitability in the Ganglion, patch-clamp recordings were made from postnatal day (P5-8) murine Spiral Ganglion neurons in vitro. We found that RMP mirrored the tonotopic threshold distribution, and contributed an additional level of heterogeneity in each cochlear location. Pharmacological experiments further indicated that threshold and RMP was coupled through the Kv1 current, which had a dual impact on both electrophysiological parameters. Whereas, hyperpolarization-activated cationic channels decoupled these two processes by primarily affecting RMP without altering threshold level. Thus, beyond mechanical and synaptic specializations, ion channel regulation of intrinsic membrane properties imbues Spiral Ganglion neurons with different excitability levels, a feature that contributes to primary auditory afferent diversity.

  • regional specification of threshold sensitivity and response time in cba caj mouse Spiral Ganglion neurons
    Journal of Neurophysiology, 2007
    Co-Authors: Qing Liu, Robin L. Davis
    Abstract:

    Previous studies of Spiral Ganglion neuron electrophysiology have shown that specific parameters differ according to cochlear location, with apical neurons being distinctly different from basal neurons. To align these features more precisely along the tonotopic axis of the cochlea, we developed a novel Spiral Ganglion culture system in which positional information is retained. Patch-clamp recordings made from neurons of known gangliotopic location revealed two basic firing pattern distributions. Membrane characteristics related to spike timing, such as accommodation, latency and onset tau, were distinctly heterogeneous, yet when averaged, they were distributed in a graded manner along the length of the cochlea. Action potential threshold levels also displayed a wide range, the averages of which were distributed nonmonotonically such that neurons with the greatest sensitivity were localized to the mid-regions of the Ganglion. These studies shed new light on the complexity and sophistication of the intrinsic firing features of Spiral Ganglion neurons. Because timing-related elements are organized in an overall tonotopic manner, it is hypothesized that they contribute to aspects of frequency-dependent acoustic processing. On the other hand, the different distribution of threshold levels, with the greatest sensitivity in the middle region of the tonotopic map, suggests that this neuronal parameter is regulated differently and thus may contribute a distinct realm of auditory sensory processing.

  • firing features and potassium channel content of murine Spiral Ganglion neurons vary with cochlear location
    The Journal of Comparative Neurology, 2002
    Co-Authors: Crista L Adamson, Michael A Reid, Janet Bowneenglish, Robin L. Davis
    Abstract:

    Neurons from varied regions of the central nervous system can show widely divergent responses to electrical stimuli that are determined by cell-specific differences in ion channel composition. The well-ordered and highly characterized peripheral auditory system allows one to explore the significance of this diversity during the final stages of postnatal development. We examined the electrophysiological features of murine Spiral Ganglion neurons in vitro at a time when recordings could be made from the cell bodies before myelination. These cells carry information about sound stimuli from hair cell receptors in the basilar membrane and are arranged tonotopically. Spiral Ganglion neuron responses to depolarizing current injection were assessed with whole-cell current clamp recordings from cells that were isolated separately from the apical and basal thirds of the mouse cochlea. These cells displayed systematic variation in their firing. Apex neurons (low frequency coding) showed longer latency, slowly adapting responses, whereas base neurons (high frequency coding) showed short latency, rapidly adapting responses to the same stimuli. This physiological diversity was mirrored by regional differences in ion channel content assessed immunohistochemically. Apex neurons had a preponderance of Kv4.2 subunits, whereas base neurons possessed greater levels of K(Ca), Kv1.1, and Kv3.1 subunits. Taken together, these results indicate that the distribution of a set of voltage-gated potassium channels may relate specifically to a particular range of coding frequencies. These studies also suggest that intrinsic properties of Spiral Ganglion neurons can contribute to the characteristic responses of the peripheral auditory system. Their potential role in development and adult function is discussed.

  • opposite actions of brain derived neurotrophic factor and neurotrophin 3 on firing features and ion channel composition of murine Spiral Ganglion neurons
    The Journal of Neuroscience, 2002
    Co-Authors: Crista L Adamson, Michael A Reid, Robin L. Davis
    Abstract:

    It is now well established that sensory neurons and receptors display characteristic morphological and electrophysiological properties tailored to their functions. This is especially evident in the auditory system, where cells are arranged tonotopically and are highly specialized for precise coding of frequency- and timing-dependent auditory information. Less well understood, however, are the mechanisms that give rise to these biophysical properties. We have provided insight into this issue by using whole-cell current-clamp recordings and immunocytochemistry to show that BDNF and NT-3, neurotrophins found normally in the cochlea, have profound effects on the firing properties and ion channel distribution of Spiral Ganglion neurons in the murine cochlea. Exposure of neurons to BDNF caused all neurons, regardless of their original cochlear position, to display characteristics of the basal neurons. Conversely, NT-3 caused cells to show the properties of apical neurons. These results are consistent with oppositely oriented gradients of these two neurotrophins and/or their high-affinity receptors along the tonotopic map, and they suggest that a combination of neurotrophins are necessary to establish the characteristic firing features of postnatal Spiral Ganglion neurons.