#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Mutation of Leads to Blurred Tonotopic Organization of Central Auditory Circuits in Mice


Millions of people suffer from debilitating hearing defects, ranging from a complete inability to detect sound to more subtle changes in how sounds are encoded by the nervous system. Many forms of deafness are due to mutations in genes that impair the development or function of hair cells, which are responsible for changing sound into electrical signals that can be processed by the brain. Both mice and humans carrying these mutations fail standard hearing tests. In contrast, very little is known about the genetic basis of central auditory processing disorders, which are poorly defined and difficult to diagnose, since these patients can still detect sounds. By finding genes that are required for the normal wiring of central auditory circuits in mice, we can investigate how changes at the circuit level affect circuit function and therefore improve our understanding of central auditory processing disorders. Here, we show that the natriuretic peptide receptor Npr2 is required to establish frequency maps in the mouse central auditory system. Surprisingly, despite a dramatic change in circuit organization, Npr2 mutant mice are still able to respond to sounds with normal sensitivity and timing, underscoring the need for better hearing diagnostic methods in mice as in humans.


Vyšlo v časopise: Mutation of Leads to Blurred Tonotopic Organization of Central Auditory Circuits in Mice. PLoS Genet 10(12): e32767. doi:10.1371/journal.pgen.1004823
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004823

Souhrn

Millions of people suffer from debilitating hearing defects, ranging from a complete inability to detect sound to more subtle changes in how sounds are encoded by the nervous system. Many forms of deafness are due to mutations in genes that impair the development or function of hair cells, which are responsible for changing sound into electrical signals that can be processed by the brain. Both mice and humans carrying these mutations fail standard hearing tests. In contrast, very little is known about the genetic basis of central auditory processing disorders, which are poorly defined and difficult to diagnose, since these patients can still detect sounds. By finding genes that are required for the normal wiring of central auditory circuits in mice, we can investigate how changes at the circuit level affect circuit function and therefore improve our understanding of central auditory processing disorders. Here, we show that the natriuretic peptide receptor Npr2 is required to establish frequency maps in the mouse central auditory system. Surprisingly, despite a dramatic change in circuit organization, Npr2 mutant mice are still able to respond to sounds with normal sensitivity and timing, underscoring the need for better hearing diagnostic methods in mice as in humans.


Zdroje

1. WickesbergRE, OertelD (1988) Tonotopic projection from the dorsal to the anteroventral cochlear nucleus of mice. J Comp Neurol 268: 389–399.

2. WickesbergRE, OertelD (1990) Delayed, frequency-specific inhibition in the cochlear nuclei of mice: a mechanism for monaural echo suppression. Journal of Neuroscience 10: 1762–1768.

3. CantNB, BensonCG (2003) Parallel auditory pathways: projection patterns of the different neuronal populations in the dorsal and ventral cochlear nuclei. Brain Research Bulletin 60: 457–474.

4. CantNB, MorestDK (1979) The bushy cells in the anteroventral cochlear nucleus of the cat. A study with the electron microscope. Neuroscience 4: 1925–1945.

5. Yin TT (2002) Neural mechanisms of encoding binaural localization cues in the auditory brainstem. In: Oertel D, Fay R, Popper A, editors. Integrative Functions in the Mammalian Auditory Pathway: Springer New York. pp. 99–159.

6. SpirouGA, RagerJ, ManisPB (2005) Convergence of auditory-nerve fiber projections onto globular bushy cells. Neuroscience 136: 843–863.

7. LauerAM, ConnellyCJ, GrahamH, RyugoDK (2013) Morphological characterization of bushy cells and their inputs in the laboratory mouse (Mus musculus) anteroventral cochlear nucleus. PLoS ONE 8: e73308.

8. BlackburnCC, SachsMB (1990) The representations of the steady-state vowel sound/e/in the discharge patterns of cat anteroventral cochlear nucleus neurons. J Neurophysiol 63: 1191–1212.

9. AlibardiL (1998) Ultrastructural and immunocytochemical characterization of commissural neurons in the ventral cochlear nucleus of the rat. Annals of Anatomy - Anatomischer Anzeiger 180: 427–438.

10. OertelD, WrightS, CaoX-J, FerragamoM, BalR (2011) The multiple functions of T stellate/multipolar/chopper cells in the ventral cochlear nucleus. Hearing Research 276: 61–69.

11. RhodeWS, SmithPH (1986) Encoding timing and intensity in the ventral cochlear nucleus of the cat. J Neurophysiol 56: 261–286.

12. GoldingNL, RobertsonD, OertelD (1995) Recordings from slices indicate that octopus cells of the cochlear nucleus detect coincident firing of auditory nerve fibers with temporal precision. Journal of Neuroscience 15: 3138–3153.

13. McGinleyMJ, LibermanMC, BalR, OertelD (2012) Generating synchrony from the asynchronous: compensation for cochlear traveling wave delays by the dendrites of individual nrainstem neurons. Journal of Neuroscience 32: 9301–9311.

14. OertelD, YoungED (2004) What's a cerebellar circuit doing in the auditory system? Trends in Neurosciences 27: 104–110.

15. YangH, Xu-FriedmanMA (2008) Relative roles of different mechanisms of depression at the mouse endbulb of Held. J Neurophysiol 99: 2510–2521.

16. CaoX-J, OertelD (2010) Auditory nerve fibers excite targets through synapses that vary in convergence, strength, and short-term plasticity. J Neurophysiol 104: 2308–2320.

17. MichalskiN, BabaiN, RenierN, PerkelDJ, ChédotalA, et al. (2013) Robo3-driven axon midline crossing conditions functional maturation of a large commissural synapse. Neuron 78: 855–868.

18. DrorAA, AvrahamKB (2009) Hearing loss: mechanisms revealed by genetics and cell biology. Annu Rev Genet 43: 411–437.

19. MooreDR (2006) Auditory processing disorder (APD)-potential contribution of mouse research. Brain Research 1091: 200–206.

20. ZengFG (2005) Perceptual consequences of disrupted auditory nerve activity. J Neurophysiol 93: 3050–3063.

21. LuCC, ApplerJM, HousemanEA, GoodrichLV (2011) Developmental profiling of spiral ganglion neurons reveals insights into auditory circuit assembly. Journal of Neuroscience 31: 10903–10918.

22. PotterLR, Abbey-HoschS, DickeyDM (2006) Natriuretic peptides, their receptors, and cyclic guanosine monophosphate-dependent signaling functions. Endocr Rev 27: 47–72.

23. SchmidtH, StonkuteA, JüttnerR, KoeslingD, FriebeA, et al. (2009) C-type natriuretic peptide (CNP) is a bifurcation factor for sensory neurons. Proc Natl Acad Sci USA 106: 16847–16852.

24. SchmidtH, StonkuteA, JüttnerR, SchäfferS, ButtgereitJ, et al. (2007) The receptor guanylyl cyclase Npr2 is essential for sensory axon bifurcation within the spinal cord. Journal of Cell Biology 179: 331–340.

25. Ter-AvetisyanG, RathjenFG, SchmidtH (2014) Bifurcation of axons from cranial sensory neurons is disabled in the absence of npr2-induced cgmp signaling. Journal of Neuroscience 34: 737–747.

26. SchmidtH, RathjenFG (2010) Signalling mechanisms regulating axonal branching in vivo. Bioessays 32: 977–985.

27. XiaC, NguyenM, GarrisonAK, ZhaoZ, WangZ, et al. (2013) CNP/cGMP signaling regulates axon branching and growth by modulating microtubule polymerization. Dev Neurobiol 73: 673–687.

28. ZhaoZ, MaL (2009) Regulation of axonal development by natriuretic peptide hormones. Proc Natl Acad Sci USA 106: 18016–18021.

29. ZhaoZ, WangZ, GuY, FeilR, HofmannF, et al. (2009) Regulate axon branching by the cyclic GMP pathway via inhibition of glycogen synthase kinase 3 in dorsal root ganglion sensory neurons. Journal of Neuroscience 29: 1350–1360.

30. BartelsCF, BukulmezH, PadayattiP, RheeDK, van Ravenswaaij-ArtsC, et al. (2004) Mutations in the transmembrane natriuretic peptide receptor NPR-B impair skeletal growth and cause acromesomelic dysplasia, type Maroteaux. Am J Hum Genet 75: 27–34.

31. MikaelianD, RubenR (1965) Development of hearing in the normal CBA-J mouse: correlation of physiological observations with behavioral responses and with cochlear anatomy. Acta Otolaryngol 59: 451–461.

32. RushtonW (1951) A theory of the effects of fibre size in medullated nerve. Journal of Physiology 115: 101–122.

33. KoundakjianEJ, ApplerJL, GoodrichLV (2007) Auditory neurons make stereotyped wiring decisions before maturation of their targets. Journal of Neuroscience 27: 14078–14088.

34. ZhangS, OertelD (1993) Tuberculoventral cells of the dorsal cochlear nucleus of mice: intracellular recordings in slices. J Neurophysiol 69: 1409–1421.

35. MelcherJR, GuinanJ, JohnJ, KnudsonIM, KiangN (1996) Generators of the brainstem auditory evoked potential in cat. II. Correlating lesion sites with waveform changes. Hearing Research 93: 28–51.

36. Parham K, Sun X-M, Kim D (2001) Noninvasive assessment of auditory function in mice: auditory brainstem response and distortion product otoacoustic emissions. In: Willott JF, editor. Handbook of Mouse Auditory Research. Boca Raton: CRC Press LLC. pp. 37–58.

37. YuanY, ShiF, YinY, TongM, LangH, et al. (2014) Ouabain-induced cochlear nerve degeneration: synaptic loss and plasticity in a mouse model of auditory neuropathy. JARO 15: 31–43.

38. EhretG (1976) Development of absolute auditory thresholds in the house mouse (Mus musculus). J Am Audiol Soc 1: 179–184.

39. TsujiT (2005) A loss-of-function mutation in natriuretic peptide receptor 2 (Npr2) gene is responsible for disproportionate dwarfism in cn/cn mouse. Journal of Biological Chemistry 280: 14288–14292.

40. OertelD, WuSH, GarbMW, DizackC (1990) Morphology and physiology of cells in slice preparations of the posteroventral cochlear nucleus of mice. J Comp Neurol 295: 136–154.

41. CaoX-J, ShatadalS, OertelD (2007) Voltage-sensitive conductances of bushy cells of the mammalian ventral cochlear nucleus. J Neurophysiol 97: 3961–3975.

42. ChandaS, Xu-FriedmanMA (2010) A low-affinity antagonist reveals saturation and desensitization in mature synapses in the auditory brain stem. J Neurophysiol 103: 1915–1926.

43. FerragamoMJ, GoldingNL, OertelD (1998) Synaptic inputs to stellate cells in the ventral cochlear nucleus. J Neurophysiol 79: 51–63.

44. WuSH, OertelD (1984) Intracellular injection with horseradish peroxidase of physiologically characterized stellate and bushy cells in slices of mouse anteroventral cochlear nucleus. Journal of Neuroscience 4: 1577–1588.

45. DoucetJR, RyugoDK (1997) Projections from the ventral cochlear nucleus to the dorsal cochlear nucleus in rats. J Comp Neurol 385: 245–264.

46. WuSH, OertelD (1987) Maturation of synapses and electrical properties of cells in the cochlear nuclei. Hearing Research 30: 99–110.

47. DunnJ, BlightA (2011) Dalfampridine: a brief review of its mechanism of action and efficacy as a treatment to improve walking in patients with multiple sclerosis. Curr Med Res Opin 27: 1415–1423.

48. CoateTM, KelleyMW (2013) Making connections in the inner ear: recent insights into the development of spiral ganglion neurons and their connectivity with sensory hair cells. Seminars in Cell and Developmental Biology 24: 460–469.

49. MaricichSM, XiaA, MathesEL, WangVY, OghalaiJS, et al. (2009) Atoh1-lineal neurons are required for hearing and for the survival of neurons in the spiral ganglion and brainstem accessory auditory nuclei. Journal of Neuroscience 29: 11123–11133.

50. FaragoAF, AwatramaniRB, DymeckiSM (2006) Assembly of the brainstem cochlear nuclear complex is revealed by intersectional and subtractive genetic fate maps. Neuron 50: 205–218.

51. MoleaD, RubelEW (2003) Timing and topography of nucleus magnocellularis innervation by the cochlear ganglion. J Comp Neurol 466: 577–591.

52. KandlerK, ClauseA, NohJ (2009) Tonotopic reorganization of developing auditory brainstem circuits. Nat Neurosci 12: 711–717.

53. TritschNX, BerglesDE (2010) Developmental regulation of spontaneous activity in the mammalian cochlea. Journal of Neuroscience 30: 1539–1550.

54. JahanI, KersigoJ, PanN, FritzschB (2010) Neurod1 regulates survival and formation of connections in mouse ear and brain. Cell Tissue Res 341: 95–110.

55. MikoIJ, NakamuraPA, HenkemeyerM, CramerKS (2007) Auditory brainstem neural activation patterns are altered in EphA4- and ephrin-B2-deficient mice. J Comp Neurol 505: 669–681.

56. CoateTM, RaftS, ZhaoX, RyanAK, IiiEBC, et al. (2012) Otic mesenchyme cells regulate spiral ganglion axon fasciculation through a pou3f4/epha4 signaling pathway. Neuron 73: 49–63.

57. ClandininTR, FeldheimDA (2009) Making a visual map: mechanisms and molecules. Curr Opin Neurobiol 19: 174–180.

58. ImaiT, YamazakiT, KobayakawaR, KobayakawaK, AbeT, et al. (2009) Pre-target axon sorting establishes the neural map topography. Science 325: 585–590.

59. LeinES, HawrylyczMJ, AoN, AyresM, BensingerA, et al. (2007) Genome-wide atlas of gene expression in the adult mouse brain. Nature 445: 168–176.

60. PienkowskiM, EggermontJJ (2012) Reversible long-term changes in auditory processing in mature auditory cortex in the absence of hearing loss induced by passive, moderate-level sound exposure. Ear Hear 33: 305–314.

61. ClauseA, NguyenT, KandlerK (2011) An acoustic startle-based method of assessing frequency discrimination in mice. Journal of Neuroscience Methods 200: 63–67.

62. KimJH, RendenR, von GersdorffH (2013) Dysmyelination of auditory afferent axons increases the jitter of action potential timing during high-frequency firing. Journal of Neuroscience 33: 9402–9407.

63. MooreJ, WesterfieldM (1983) Action potential propagation and threshold parameters in inhomogeneous regions of squid axons. Journal of Physiology 336: 285–300.

64. HindSE, Haines-BazrafshanR, BentonCL, BrassingtonW, TowleB, et al. (2011) Prevalence of clinical referrals having hearing thresholds within normal limits. Int J Audiol 50: 708–716.

65. AhmmedAU, AhmmedAA, BathJR, FergusonMA, PlackCJ, et al. (2014) Assessment of children with suspected auditory processing disorder: a factor analysis study. Ear Hear 35: 295–305.

66. HamaH, KurokawaH, KawanoH, AndoR, ShimogoriT, et al. (2011) Scale: a chemical approach for fluorescence imaging and reconstruction of transparent mouse brain. Nat Neurosci 14: 1481–1488.

67. del RioT, NishitaniAM, YuW-M, GoodrichLV (2013) In vivo analysis of lrig genes reveals redundant and independent functions in the inner ear. PLoS Genet 9: e1003824.

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2014 Číslo 12
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#