Single-Cell RNA Analysis of Type I Spiral Ganglion Neurons Reveals a Population in the Cochlea

Overview

Journal Front Mol Neurosci

Specialty Molecular Biology

Date 2020 Jun 12

PMID 32523514

Citations 12

Authors

Fiorella Carla Grandi

Lara De Tomasi

Mirna Mustapha

Affiliations

Soon will be listed here.

Abstract

In the mature cochlea, each inner hair cell (IHC) is innervated by multiple spiral ganglion neurons of type I (SGNI). SGNIs are morphologically and electro-physiologically diverse. Also, they differ in their susceptibility to noise insult. However, the molecular underpinnings of their identity and physiological differences remain poorly understood. In this study, we developed a novel triple transgenic mouse, which enabled the isolation of pure populations of SGNIs and the analysis of a 96-gene panel single-cell qPCR. We found three distinct populations of Type I SGNs, which were marked by their exclusive expression of , or , respectively, at postnatal days P3, P8, and P12. Our data suggest that afferent SGN subtypes are established genetically before the onset of hearing and that the expression of key physiological markers, such as ion channels, is heterogeneous and may be underlying the heterogeneous firing proprieties of SGNIs.

Citing Articles

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References

Froud K, Wong A, Cederholm J, Klugmann M, Sandow S, Julien J . Type II spiral ganglion afferent neurons drive medial olivocochlear reflex suppression of the cochlear amplifier. Nat Commun. 2015; 6:7115. PMC: 4432632. DOI: 10.1038/ncomms8115. View

McLenachan S, Goldshmit Y, Fowler K, Voullaire L, Holloway T, Turnley A . Transgenic mice expressing the Peripherin-EGFP genomic reporter display intrinsic peripheral nervous system fluorescence. Transgenic Res. 2008; 17(6):1103-16. DOI: 10.1007/s11248-008-9210-7. View

Chen X, Yuan L, Zhao C, Birnbaum S, Frick A, Jung W . Deletion of Kv4.2 gene eliminates dendritic A-type K+ current and enhances induction of long-term potentiation in hippocampal CA1 pyramidal neurons. J Neurosci. 2006; 26(47):12143-51. PMC: 6675426. DOI: 10.1523/JNEUROSCI.2667-06.2006. View

Koo S, Hill J, Hwang C, Lin Z, Millen K, Wu D . Lmx1a maintains proper neurogenic, sensory, and non-sensory domains in the mammalian inner ear. Dev Biol. 2009; 333(1):14-25. PMC: 3400700. DOI: 10.1016/j.ydbio.2009.06.016. View

Jung J, Zhang K, Wang Z, McMurray M, Tkaczuk A, Ogawa Y . Semaphorin-5B Controls Spiral Ganglion Neuron Branch Refinement during Development. J Neurosci. 2019; 39(33):6425-6438. PMC: 6697390. DOI: 10.1523/JNEUROSCI.0113-19.2019. View

Nayagam B, Muniak M, Ryugo D . The spiral ganglion: connecting the peripheral and central auditory systems. Hear Res. 2011; 278(1-2):2-20. PMC: 3152679. DOI: 10.1016/j.heares.2011.04.003. View

Hafidi A, Despres G, ROMAND R . Ontogenesis of type II spiral ganglion neurons during development: peripherin immunohistochemistry. Int J Dev Neurosci. 1993; 11(4):507-12. DOI: 10.1016/0736-5748(93)90024-8. View

Berglund A, Ryugo D . Hair cell innervation by spiral ganglion neurons in the mouse. J Comp Neurol. 1987; 255(4):560-70. DOI: 10.1002/cne.902550408. View

Huang Y, Hill J, Yatteau A, Wong L, Jiang T, Petrovic J . Reciprocal Negative Regulation Between Lmx1a and Lmo4 Is Required for Inner Ear Formation. J Neurosci. 2018; 38(23):5429-5440. PMC: 5990987. DOI: 10.1523/JNEUROSCI.2484-17.2018. View

10.

Nichols D, Pauley S, Jahan I, Beisel K, Millen K, Fritzsch B . Lmx1a is required for segregation of sensory epithelia and normal ear histogenesis and morphogenesis. Cell Tissue Res. 2008; 334(3):339-58. PMC: 2654344. DOI: 10.1007/s00441-008-0709-2. View

11.

Konirova J, Oltova J, Corlett A, Kopycinska J, Kolar M, Bartunek P . Modulated DISP3/PTCHD2 expression influences neural stem cell fate decisions. Sci Rep. 2017; 7:41597. PMC: 5278513. DOI: 10.1038/srep41597. View

12.

Kujawa S, Liberman M . Synaptopathy in the noise-exposed and aging cochlea: Primary neural degeneration in acquired sensorineural hearing loss. Hear Res. 2015; 330(Pt B):191-9. PMC: 4567542. DOI: 10.1016/j.heares.2015.02.009. View

13.

Welker C, Woolsey T . Structure of layer IV in the somatosensory neocortex of the rat: description and comparison with the mouse. J Comp Neurol. 1974; 158(4):437-53. DOI: 10.1002/cne.901580405. View

14.

Qian D, Jones C, Rzadzinska A, Mark S, Zhang X, Steel K . Wnt5a functions in planar cell polarity regulation in mice. Dev Biol. 2007; 306(1):121-33. PMC: 1978180. DOI: 10.1016/j.ydbio.2007.03.011. View

15.

Huang L, Hu F, Feng L, Luo X, Liang G, Zeng X . Bhlhb5 is required for the subtype development of retinal amacrine and bipolar cells in mice. Dev Dyn. 2013; 243(2):279-89. PMC: 4100943. DOI: 10.1002/dvdy.24067. View

16.

Shinoda Y, Sadakata T, Nakao K, Katoh-Semba R, Kinameri E, Furuya A . Calcium-dependent activator protein for secretion 2 (CAPS2) promotes BDNF secretion and is critical for the development of GABAergic interneuron network. Proc Natl Acad Sci U S A. 2010; 108(1):373-8. PMC: 3017206. DOI: 10.1073/pnas.1012220108. View

17.

Millonig J, Millen K, Hatten M . The mouse Dreher gene Lmx1a controls formation of the roof plate in the vertebrate CNS. Nature. 2000; 403(6771):764-9. DOI: 10.1038/35001573. View

18.

Browne L, Smith K, Jagger D . Identification of Persistent and Resurgent Sodium Currents in Spiral Ganglion Neurons Cultured from the Mouse Cochlea. eNeuro. 2017; 4(6). PMC: 5684619. DOI: 10.1523/ENEURO.0303-17.2017. View

19.

Shibata R, Nakahira K, Shibasaki K, Wakazono Y, Imoto K, Ikenaka K . A-type K+ current mediated by the Kv4 channel regulates the generation of action potential in developing cerebellar granule cells. J Neurosci. 2000; 20(11):4145-55. PMC: 6772624. View

20.

Guaiquil V, Pan Z, Karagianni N, Fukuoka S, Alegre G, Rosenblatt M . VEGF-B selectively regenerates injured peripheral neurons and restores sensory and trophic functions. Proc Natl Acad Sci U S A. 2014; 111(48):17272-7. PMC: 4260560. DOI: 10.1073/pnas.1407227111. View