Time-dependent activity of primary auditory neurons in the presence of neurotrophins and antibiotics

Cai, Helen; Gillespie, Lisa N; Wright, Tess; Brown, William G. A.; Minter, Ricki L.; Nayagam, Bryony A; O’Leary, Stephen; Needham, Karina

doi:10.1016/j.heares.2017.04.014

Cited by 6 publications

(8 citation statements)

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“…One possibility is that like in sciatic nerve SCs, cultured cochlear SGCs lose Kir4.1 channels in vitro , and then upregulate outwardly rectifying currents. Although our cultures were limited to 3 DIV, changes in the membrane properties of SGNs within cochlear cultures have been observed over a similar time frame (Cai et al., 2017).…”

Section: Discussionmentioning

confidence: 60%

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Divergent membrane properties of mouse cochlear glial cells around hearing onset

Smith

Murphy

Jagger

2020

J of Neuroscience Research

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Spiral ganglion neurons (SGNs) are the primary afferent neurons of the auditory system, and together with their attendant glia, form the auditory nerve. Within the cochlea, satellite glial cells (SGCs) encapsulate the cell body of SGNs, whereas Schwann cells (SCs) wrap their peripherally-and centrally-directed neurites. Despite their likely importance in auditory nerve function and homeostasis, the physiological properties of auditory glial cells have evaded description. Here, we characterized the voltage-activated membrane currents of glial cells from the mouse cochlea. We identified a prominent weak inwardly rectifying current in SGCs within cochlear slice preparations (postnatal day P5-P6), which was also present in presumptive SGCs within dissociated cultures prepared from the cochleae of hearing mice (P14-P15). Pharmacological block by Ba 2+ and desipramine suggested that channels belonging to the Kir4 family mediated the weak inwardly rectifying current, and post hoc immunofluorescence implicated the involvement of Kir4.1 subunits. Additional electrophysiological profiles were identified for glial cells within dissociated cultures, suggesting that glial subtypes may have specific membrane properties to support distinct physiological roles. Immunofluorescence using fixed cochlear sections revealed that although Kir4.1 is restricted to SGCs after the onset of hearing, these channels are more widely distributed within the glial population earlier in postnatal development (i.e., within both SGCs and SCs). The decrease in Kir4.1 immunofluorescence during SC maturation was coincident with a reduction of Sox2 expression and advancing neurite myelination. The data suggest a diversification of glial properties occurs in preparation for sound-driven activity in the auditory nerve.

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Section: Discussionmentioning

confidence: 60%

“…Although our cultures were limited to 3 DIV, changes in the membrane properties of SGNs within cochlear cultures have been observed over a similar time frame (Cai et al, 2017).…”

Section: Heterogeneous Membrane Properties Of Cochlear Glial Cellsmentioning

confidence: 79%

Divergent membrane properties of mouse cochlear glial cells around hearing onset

Smith

Murphy

Jagger

2020

J of Neuroscience Research

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“…(Lv et al, 2012), may lie in the dissociated primary culture of SG itself, which results in rather low neuronal survival (Vieira et al, 2007). Moreover, because type I SG neurons forming subclasses Ia, Ib, and Ic are molecularly and physiologically heterogeneous (Petitpré et al, 2018; Shrestha et al, 2018; Sun et al, 2018), subtle differences in dissociation protocols or chemicals may have resulted in a differential survival of these subclasses (Liu et al, 2016; Browne et al, 2017; Cai et al, 2017). Differential survival of subclasses may also explain the heterogeneity in our I Ca values for a given genotype and age.…”

Section: Discussionmentioning

confidence: 99%

Deletion of the Ca2+ Channel Subunit α2δ3 Differentially Affects Cav2.1 and Cav2.2 Currents in Cultured Spiral Ganglion Neurons Before and After the Onset of Hearing

Stephani

Scheuer

Eckrich

et al. 2019

Front. Cell. Neurosci.

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Voltage-gated Ca 2+ channels are composed of a pore-forming α 1 subunit and auxiliary β and α 2 δ subunits, which modulate Ca 2+ current properties and channel trafficking. So far, the partial redundancy and specificity of α 1 for α 2 δ subunits in the CNS have remained largely elusive. Mature spiral ganglion (SG) neurons express α 2 δ subunit isoforms 1, 2, and 3 and multiple Ca 2+ channel subtypes. Differentiation and in vivo functions of their endbulb of Held synapses, which rely on presynaptic P/Q channels ( Lin et al., 2011 ), require the α 2 δ3 subunit ( Pirone et al., 2014 ). This led us to hypothesize that P/Q channels may preferentially co-assemble with α 2 δ3. Using a dissociated primary culture, we analyzed the effects of α 2 δ3 deletion on somatic Ca 2+ currents ( I Ca ) of SG neurons isolated at postnatal day 20 (P20), when the cochlea is regarded to be mature. P/Q currents were the dominating steady-state Ca 2+ currents (54% of total) followed by T-type, L-type, N-type, and R-type currents. Deletion of α 2 δ3 reduced P/Q- and R-type currents by 60 and 38%, respectively, whereas L-type, N-type, and T-type currents were not altered. A subset of I Ca types was also analyzed in SG neurons isolated at P5, i.e., before the onset of hearing (P12). Both L-type and N-type current amplitudes of wildtype SG neurons were larger at P5 compared with P20. Deletion of α 2 δ3 reduced L-type and N-type currents by 23 and 44%, respectively. In contrast, small P/Q currents, which were just being up-regulated at P5, were unaffected by the lack of α 2 δ3. In summary, α 2 δ3 regulates amplitudes of L- and N-type currents of immature cultured SG neurons, whereas it regulates P/Q- and R-type currents at P20. Our data indicate a developmental switch from dominating somatic N- to P/Q-type currents in cultured SG neurons. A switch from N- to P/Q-type channels, which has been observed at several central synapses, may also occur at developing endbulbs of Held. In this case, reduction of both neonatal N- (P5) and more mature P/Q-type currents (around/after hearing onset) may contribute to the impaired morphology and function of endbulb synapses in α 2 δ3-deficient mice.

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“…Additionally, FpClass PPI tool data indicate the possible interaction of APP with 54 transcription factors. On the other hand, the intersection of the effects of both Aβ and antibiotics on neuronal excitability or firing mechanisms might indicate that both are involved. , …”

Section: Discussionmentioning

confidence: 99%

Vitamin D Receptor Regulates Amyloid Beta 1–42 Production with Protein Disulfide Isomerase A3

Gezen-Ak

Atasoy

Candaş

et al. 2017

ACS Chem. Neurosci.

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The challenge of understanding the biology of neuronal amyloid processing could provide a basis for understanding the amyloid pathology in Alzheimer's disease (AD). Based on our previous studies, we have suggested that AD might be the consequence of a hormonal imbalance in which the critical hormone is vitamin D. The present study primarily focused on the creation of a condition that prevents the genomic or nongenomic action of vitamin D by disrupting vitamin D receptors (VDR or PDIA3/1,25MARRS); the effects of these disruptions on the series of proteins involved in secretases that play a crucial role in amyloid pathology and on amyloid beta (Aβ) production in primary cortical neurons were observed. VDR and PDIA3/1,25MARRS genes were silenced separately or simultaneously in E16 primary rat cortical neurons. The expression of target genes involved in APP processing, including Presenilin1, Presenilin2, Nicastrin, BACE1, ADAM10, and APP, was investigated with qRT-PCR and Western blot in this model. 1,25-Dihydroxyvitamin D treatments were used to verify any transcriptional regulation data gathered from siRNA treatments by determining the mRNA expression of the target genes. Immunofluorescence labeling was used for the verification of silencing experiments and intracellular Aβ1-42 production. Extracellular Aβ1-42 level was assessed with ELISA. mRNA and protein expression results showed that 1,25-dihydroxyvitamin D might affect the transcriptional regulation of the genes involved in APP processing. The intracellular and extracellular Aβ1-42 measurements in our study support this suggestion. Consequently, we suggest that 1,25-dihydroxyvitamin D and its receptors are important parts of the amyloid processing pathway in neurons.

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Time-dependent activity of primary auditory neurons in the presence of neurotrophins and antibiotics

Cited by 6 publications

References 58 publications

Divergent membrane properties of mouse cochlear glial cells around hearing onset

Divergent membrane properties of mouse cochlear glial cells around hearing onset

Deletion of the Ca2+ Channel Subunit α2δ3 Differentially Affects Cav2.1 and Cav2.2 Currents in Cultured Spiral Ganglion Neurons Before and After the Onset of Hearing

Vitamin D Receptor Regulates Amyloid Beta 1–42 Production with Protein Disulfide Isomerase A3

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