Classification of neurons in the adult mouse cochlear nucleus: Linear discriminant analysis

Autoři: Paul B. Manis aff001;  Michael R. Kasten aff001;  Ruili Xie aff002
Působiště autorů: Department of Otolaryngology/Head and Neck Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America aff001;  Department of Otolaryngology, The Ohio State University, Columbus, Ohio, United States of America aff002
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223137


The cochlear nucleus (CN) transforms the spike trains of spiral ganglion cells into a set of sensory representations that are essential for auditory discriminations and perception. These transformations require the coordinated activity of different classes of neurons that are embryologically derived from distinct sets of precursors. Decades of investigation have shown that the neurons of the CN are differentiated by their morphology, neurotransmitter receptors, ion channel expression and intrinsic excitability. In the present study we have used linear discriminant analysis (LDA) to perform an unbiased analysis of measures of the responses of CN neurons to current injections to objectively categorize cells on the basis of both morphology and physiology. Recordings were made from cells in brain slices from CBA/CaJ mice and a transgenic mouse line, NF107, crossed against the Ai32 line. For each cell, responses to current injections were analyzed for spike rate, spike shape, input resistance, resting membrane potential, membrane time constant, hyperpolarization-activated sag and time constant. Cells were filled with dye for morphological classification, and visually classified according to published accounts. The different morphological classes of cells were separated with the LDA. Ventral cochlear nucleus (VCN) bushy cells, planar multipolar (T-stellate) cells, and radiate multipolar (D-stellate) cells were in separate clusters and separate from all of the neurons from the dorsal cochlear nucleus (DCN). Within the DCN, the pyramidal cells and tuberculoventral cells were largely separated from a distinct cluster of cartwheel cells. principal axes, whereas VCN cells were in 3 clouds approximately orthogonal to this plane. VCN neurons from the two mouse strains overlapped but were slightly separated, indicating either a strain dependence or differences in slice preparation methods. We conclude that cochlear nucleus neurons can be objectively distinguished based on their intrinsic electrical properties, but such distinctions are still best aided by morphological identification.

Klíčová slova:

Action potentials – Linear discriminant analysis – Membrane potential – Neuronal dendrites – Neurons – Principal component analysis – Auditory pathway – Pyramidal cells


1. Rothman JS, Manis PB. Differential expression of three distinct potassium currents in the ventral cochlear nucleus. J Neurophysiol. 2003;89: 3070–3082. doi: 10.1152/jn.00125.2002 12783951

2. Rothman JS, Manis PB. The roles potassium currents play in regulating the electrical activity of ventral cochlear nucleus neurons. J Neurophysiol. 2003;89: 3097–3113. doi: 10.1152/jn.00127.2002 12783953

3. Cao X-J, Oertel D. The magnitudes of hyperpolarization-activated (Ih) and low-voltage-activated potassium (IKL) currents co-vary in neurons of the ventral cochlear nucleus. J Neurophysiol. 2011;106: 630–640. doi: 10.1152/jn.00015.2010 21562186

4. Oertel D. Synaptic responses and electrical properties of cells in brain slices of the mouse anteroventral cochlear nucleus. J Neurosci. 1983;3: 2043–2053. doi: 10.1523/JNEUROSCI.03-10-02043.1983 6619923

5. Wu SH, Oertel D. Intracellular injection with horseradish peroxidase of physiologically characterized stellate and bushy cells in slices of mouse anteroventral cochlear nucleus. J Neurosci. 1984;4: 1577–1588. doi: 10.1523/JNEUROSCI.04-06-01577.1984 6726347

6. Oertel D, Wu SH, Garb MW, Dizack C. Morphology and physiology of cells in slice preparations of the posteroventral cochlear nucleus of mice. J Comp Neurol. 1990;295: 136–154. doi: 10.1002/cne.902950112 2341631

7. Zhang S, Oertel D. Cartwheel and superficial stellate cells of the dorsal cochlear nucleus of mice: intracellular recordings in slices. J Neurophysiol. 1993;69: 1384–1397. doi: 10.1152/jn.1993.69.5.1384 8389821

8. Zhang S, Oertel D. Giant cells of the dorsal cochlear nucleus of mice: intracellular recordings in slices. J Neurophysiol. 1993;69: 1384–1397. doi: 10.1152/jn.1993.69.5.1384 8389821

9. Zhang S, Oertel D. Neuronal circuits associated with the output of the dorsal cochlear nucleus through fusiform cells. J Neurophysiol. 1994;71: 914–930. doi: 10.1152/jn.1994.71.3.914 8201432

10. Manis PB, Spirou GA, Wright DD, Paydar S, Ryvgo DK. Physiology and morphology of complex spiking neurons in the guinea pig dorsal cochlear nucleus. J Comp Neurol. 1994;348: 261–276. doi: 10.1002/cne.903480208 7814691

11. Xie R, Manis PB. Radiate and planar multipolar neurons of the mouse anteroventral cochlear nucleus: Intrinsic excitability and characterization of their auditory nerve input. Front Neural Circuits. 2017;11: 77. doi: 10.3389/fncir.2017.00077 29093666

12. Kuo SP, Lu H-W, Trussell LO. Intrinsic and synaptic properties of vertical cells of the mouse dorsal cochlear nucleus. J Neurophysiol. 2012;108: 1186–1198. doi: 10.1152/jn.00778.2011 22572947

13. Druckmann S, Hill S, Schürmann F, Markram H, Segev I. A Hierarchical Structure of Cortical Interneuron Electrical Diversity Revealed by Automated Statistical Analysis. Cereb Cortex. 2013;23: 2994–3006. doi: 10.1093/cercor/bhs290 22989582

14. Tavakoli A, Schmaltz A, Schwarz D, Margrie TW, Schaefer AT, Kollo M. Quantitative Association of Anatomical and Functional Classes of Olfactory Bulb Neurons. J Neurosci. 2018;38: 7204–7220. doi: 10.1523/JNEUROSCI.0303-18.2018 29976625

15. Tripathy SJ, Burton SD, Geramita M, Gerkin RC, Urban NN. Brain-wide analysis of electrophysiological diversity yields novel categorization of mammalian neuron types. J Neurophysiol. 2015;113: 3474–3489. doi: 10.1152/jn.00237.2015 25810482

16. Typlt M, Englitz B, Sonntag M, Dehmel S, Kopp-Scheinpflug C, Ruebsamen R. Multidimensional characterization and differentiation of neurons in the anteroventral cochlear nucleus. PLoS One. 2012;7: e29965. doi: 10.1371/journal.pone.0029965 22253838

17. Rao CR. The Utilization of Multiple Measurements in Problems of Biological Classification. J R Stat Soc Ser B. 1948;10: 159–203. doi: 10.2307/2983775

18. Gong S, Zheng C, Doughty ML, Losos K, Didkovsky N, Schambra UB, et al. A gene expression atlas of the central nervous system based on bacterial artificial chromosomes. Nature. 2003;425: 917–925. doi: 10.1038/nature02033 14586460

19. Madisen L, Mao T, Koch H, Zhuo J, Berenyi A, Fujisawa S, et al. A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing. Nat Neurosci. 2012;15: 793–802. doi: 10.1038/nn.3078 22446880

20. Xie R, Manis PB. Target-Specific IPSC Kinetics Promote Temporal Processing in Auditory Parallel Pathways. J Neurosci. 2013;33: 1598–1614. doi: 10.1523/JNEUROSCI.2541-12.2013 23345233

21. Ting JT, Daigle TL, Chen Q, Feng G. Acute Brain Slice Methods for Adult and Aging Animals: Application of Targeted Patch Clamp Analysis and Optogenetics. Methods Mol Biol. 2014;1183: 221–242. doi: 10.1007/978-1-4939-1096-0_14 25023312

22. Campagnola L, Kratz MB, Manis PB. ACQ4: an open-source software platform for data acquisition and analysis in neurophysiology research. Front Neuroinform. 2014;8: 3. doi: 10.3389/fninf.2014.00003 24523692

23. Fujino K, Oertel D. Cholinergic modulation of stellate cells in the mammalian ventral cochlear nucleus. J Neurosci. 2001;21: 7372–7383. doi: 10.1523/JNEUROSCI.21-18-07372.2001 11549747

24. Doucet JR, Ryugo DK. Projections from the ventral cochlear nucleus to the dorsal cochlear nucleus in rats. J Comp Neurol. 1997;385: 245–264. 9268126

25. Campagnola L, Manis PB. A Map of Functional Synaptic Connectivity in the Mouse Anteroventral Cochlear Nucleus. J Neurosci. 2014;34: 2214–2230. doi: 10.1523/JNEUROSCI.4669-13.2014 24501361

26. Lauer AM, Connelly CJ, Graham H, Ryugo DK. Morphological Characterization of Bushy Cells and Their Inputs in the Laboratory Mouse (Mus musculus) Anteroventral Cochlear Nucleus. PLoS One. 2013;8: e73308. doi: 10.1371/journal.pone.0073308 23991186

27. Cant NB, Morest DK. Organization of the neuorns in the anterior division of the anteroventral cochlear nucleus of the cat. Light-microscopic observations. Neuroscience. 1979;4: 1909–1923. doi: 10.1016/0306-4522(79)90065-4 530438

28. Webster DB, Trune DR. Cochlear nuclear complex of mice. Am J Anat. 1982;163: 103–130. doi: 10.1002/aja.1001630202 7072613

29. Tolbert LP, Morest DK, Yurgelun-Todd DA. The neuronal architecture of the anteroventral cochlear nucleus of the cat in the region of the cochlear nerve root: horseradish peroxidase labelling of identified cell types. Neuroscience. 1982;7: 3031–3052. doi: 10.1016/0306-4522(82)90228-7 6298659

30. Blackstad TW, Osen KK, Mugnaini E. Pyramidal neurones of the dorsal cochlear nucleus: A golgi and computer reconstruction study in cat. Neuroscience. 1984;13: 827–854. doi: 10.1016/0306-4522(84)90099-x 6527780

31. Lorente de No R. The Primary Acoustic Nuclei. NY: Raven Press; 1981.

32. Molitor SC, Manis PB. Dendritic Ca 2+ Transients Evoked by Action Potentials in Rat Dorsal Cochlear Nucleus Pyramidal and Cartwheel Neurons. J Neurophysiol. 2003;89: 2225–2237. doi: 10.1152/jn.00709.2002 12612001

33. Mugnaini E, Berrebi A, Dahl A, Morgan J. The polypeptide PEP-19 is a marker for Purkinje neurons in cerebellar cortex and cartwheel neurons in the dorsal cochlear nucleus. Arch Ital Biol. 1987;126: 41–67. Available: papers2://publication/uuid/CE9BAF51-50D1-4BC3-BA4B-D527E29C0730 3449006

34. Wouterlood FG, Mugnaini E. Cartwheel neurons of the dorsal cochlear nucleus: A Golgi-electron microscopic study in rat. J Comp Neurol. 1984;227: 136–157. doi: 10.1002/cne.902270114 6088594

35. Zhang S, Oertel D. Tuberculoventral cells of the dorsal cochlear nucleus of mice: intracellular recordings in slices. J Neurophysiol. 1993;69: 1409–1421. doi: 10.1152/jn.1993.69.5.1409 8389823

36. Manis PB. Membrane properties and discharge characteristics of guinea pig dorsal cochlear nucleus neurons studied in vitro. J Neurosci. 1990;10: 2338–2351. doi: 10.1523/JNEUROSCI.10-07-02338.1990 2376777

37. Hirsch JA, Oertel D. Intrinsic properties of neurones in the dorsal cochlear nucleus of mice, in vitro. J Physiol. 1988;396: 535–548. doi: 10.1113/jphysiol.1988.sp016976 2457693

38. Kanold PO, Manis PB. Transient Potassium Currents Regulate the Discharge Patterns of Dorsal Cochlear Nucleus Pyramidal Cells. J Neurosci. 1999;19: 2195–2208. doi: 10.1523/JNEUROSCI.19-06-02195.1999 10066273

39. Street SE, Manis PB. Action potential timing precision in dorsal cochlear nucleus pyramidal cells. J Neurophysiol. 2007;97: 4162–4172. doi: 10.1152/jn.00469.2006 17442767

40. Leao RM, Li S, Doiron B, Tzounopoulos T. Diverse levels of an inwardly rectifying potassium conductance generate heterogeneous neuronal behavior in a population of dorsal cochlear nucleus pyramidal neurons. J Neurophysiol. 2012/03/02. 2012;107: 3008–3019. doi: 10.1152/jn.00660.2011 22378165

41. Weedman DL, Pongstaporn T, Ryugo DK. Ultrastructural study of the granule cell domain of the cochlear nucleus in rats: mossy fiber endings and their targets. J Comp Neurol. 1996;369: 345–360. doi: 10.1002/(SICI)1096-9861(19960603)369:3<345::AID-CNE2>3.0.CO;2-5 8743417

42. Apostolides PF, Trussell LO. Superficial stellate cells of the dorsal cochlear nucleus. Front Neural Circuits. 2014;8: 1–9. doi: 10.3389/fncir.2014.00001

43. Mugnaini E, Sekerková G, Martina M. The unipolar brush cell: A remarkable neuron finally receiving deserved attention. Brain Res Rev. 2011;66: 220–245. doi: 10.1016/j.brainresrev.2010.10.001 20937306

44. Francis HW, Manis PB. Effects of deafferentation on the electrophysiology of ventral cochlear nucleus neurons. Hear Res. 2000;149: 91–105. doi: 10.1016/s0378-5955(00)00165-9 11033249

45. Cao X-J, Shatadal S, Oertel D. Voltage-sensitive conductances of bushy cells of the Mammalian ventral cochlear nucleus. J Neurophysiol. 2007;97: 3961–3975. doi: 10.1152/jn.00052.2007 17428908

Článek vyšel v časopise


2019 Číslo 10

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…


Zvyšte si kvalifikaci online z pohodlí domova

Léčba bolesti v ordinaci praktického lékaře
nový kurz
Autoři: MUDr. PhDr. Zdeňka Nováková, Ph.D.

Revmatoidní artritida: včas a k cíli
Autoři: MUDr. Heřman Mann

Jistoty a nástrahy antikoagulační léčby aneb kardiolog - neurolog - farmakolog - nefrolog - právník diskutují
Autoři: doc. MUDr. Štěpán Havránek, Ph.D., prof. MUDr. Roman Herzig, Ph.D., doc. MUDr. Karel Urbánek, Ph.D., prim. MUDr. Jan Vachek, MUDr. et Mgr. Jolana Těšínová, Ph.D.

Léčba akutní pooperační bolesti
Autoři: doc. MUDr. Jiří Málek, CSc.

Nové antipsychotikum kariprazin v léčbě schizofrenie
Autoři: prof. MUDr. Cyril Höschl, DrSc., FRCPsych.

Všechny kurzy
Kurzy Doporučená témata Časopisy
Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.


Nemáte účet?  Registrujte se