97:3961-3975, 2007. First published Apr 11, 2007; doi:10.1152/jn.00052.2007 J NeurophysiolXiao-Jie Cao, Shalini Shatadal and Donata Oertel You might find this additional information useful...119 articles, 65 of which you can access free at: This article cites http://jn.physiology.org/cgi/content/full/97/6/3961#BIBLincluding high-resolution figures, can be found at: Updated information and services http://jn.physiology.org/cgi/content/full/97/6/3961 can be found at: Journal of Neurophysiologyabout Additional material and information http://www.the-aps.org/publications/jnThis information is current as of June 6, 2007 . http://www.the-aps.org/.American Physiological Society. ISSN: 0022-3077, ESSN: 1522-1598. Visit our website at (monthly) by the American Physiological Society, 9650 Rockville Pike, Bethesda MD 20814-3991. Copyright © 2005 by the publishes original articles on the function of the nervous system. It is published 12 times a yearJournal of Neurophysiology on June 6, 2007 jn.physiology.orgDownloaded fromVoltage-Sensitive Conductances of Bushy Cells of the Mammalian VentralCochlear NucleusXiao-Jie Cao, Shalini Shatadal, and Donata OertelDepartment of Physiology, University of Wisconsin School of Medicine, Madison, WisconsinSubmitted 15 January 2007; accepted in final form 6 April 2007Cao X-J, Shatadal S, Oertel D. Voltage-sensitive conductances ofbushy cells of the mammalian ventral cochlear nucleus. J Neuro-physiol 97: 3961–3975, 2007. First published April 11, 2007;doi:10.1152/jn.00052.2007. Bushy cells in the ventral cochlear nu-cleus convey firing of auditory nerve fibers to neurons in the superiorolivary complex that compare the timing and intensity of sounds at thetwo ears and enable animals to localize sound sources in the horizon-tal plane. Three voltage-sensitive conductances allow bushy cells toconvey acoustic information with submillisecond temporal precision.All bushy cells have a low-voltage-activated,␣-dendrotoxin (␣-DTX)-sensitive K⫹conductance (gKL) that was activated by depolar-ization past –70 mV, was half-activated at –39.0 ⫾ 1.7 (SE) mV, andinactivated ⬃60% over 5 s. Maximal gKLvaried between 40 and 150nS (mean: 80.8 ⫾ 16.7 nS). An␣-DTX-insensitive, tetraethylammo-nium (TEA)-sensitive, K⫹conductance (gKH) was activated at volt-ages positive to – 40 mV, was half-activated at –18.1 ⫾ 3.8 mV, andinactivated by 90% over 5 s. Maximal gKHvaried between 35 and 80nS (mean: 58.2 ⫾ 6.5 nS). A ZD7288-sensitive, mixed cation con-ductance (gh) was activated by hyperpolarization greater than – 60 mVand half-activated at – 83.1 ⫾ 1.1 mV. Maximum ghranged between14.5 and 56.6 nS (mean: 30.0 ⫾ 5.5 nS). 8-Br-cAMP shifted thevoltage sensitivity of ghpositively. Changes in temperature stablyaltered the steady-state magnitude of Ih. Both gKLand gKHcontributeto repolarizing action potentials and to sharpening synaptic potentials.Those cells with the largest ghand the largest gKLfired least at theonset of a depolarization, required the fastest depolarizations to fire,and tended to be located nearest the nerve root.INTRODUCTIONBushy cells receive information about the timing and finestructure of sounds from the temporal firing patterns in audi-tory nerve fibers and convey it to the superior olivary complex.Neurons in the MSO use phase-locking by large sphericalbushy cells in the encoding of low-frequency sounds to com-pute the interaural phase and thus the relative time of arrival, ofsounds at the two ears (Joris et al. 1998; Yin 2002). Neurons inthe LSO compare the timing and frequency of excitation fromipsilateral small spherical bushy (Cant and Casseday 1986) andT (or planar) stellate cells (Doucet and Ryugo 2003) withinhibition from the medial nucleus of the trapezoid body(MNTB) that reflects the timing and frequency of firing ofcontralateral globular bushy cells in responses to high-fre-quency sounds to compute the relative intensities of sounds atthe two ears (Tollin and Yin 2005; Yin 2002).The three subtypes of bushy cells have been described inmammals that differ subtly in size and histological staining aswell as in projection patterns: large spherical, small spherical,and globular bushy cells (Brawer et al. 1974; Cant and Casse-day 1986; Cant and Morest 1979a,b; Osen 1969; Tolbert andMorest 1982a,b; Tolbert et al. 1982). Large spherical bushycells in the rostral anterior VCN encode mainly low-frequencysounds and project to the lateral tuft in the ipsilateral and themedial tuft of dendrites of neurons in the contralateral MSO(Smith et al. 1993). Mice have little low-frequency hearing(Ehret 1974), a small and inconspicuous MSO and also fewlarge spherical bushy cells (Willard and Ryugo 1983). In micemost bushy cells are of the globular and small sphericalsubtypes. Globular bushy cells are generally located near theroot of the auditory nerve (Liberman 1991, 1993; Spirou et al.1990; Tolbert and Morest 1982a,b; Tolbert et al. 1982), encodesounds of higher frequencies, and project to the MNTBthrough large axons that end in very large terminals, thecalyces of Held (Brownell 1975; Liberman 1991; Sento andRyugo 1989; Smith et al. 1991; Tolbert et al. 1982). Smallspherical bushy cells are least well understood. Many project tothe ipsilateral LSO, but it is unclear whether small sphericalbushy cells or T stellate cells are the predominant source ofipsilateral excitation (Cant and Casseday 1986; Doucet andRyugo 2003). Several lines of evidence indicate that globularand small spherical bushy cells are distinct. First, individuallylabeled globular bushy cells do not innervate the LSO (Smithet al. 1991). Second, monosynaptic, ipsilateral excitation of theLSO is matched in timing with disynaptic, contralateral inhi-bition through the MNTB and is therefore likely to be mediatedthrough more slowly conducting axons (Joris and Yin 1995). Incats, the axons of globular bushy cells have exceptionally largediameters, small spherical bushy cells presumably have axonsof intermediate diameter, and axons of T stellate cells havesmall diameters (Brownell 1975; Joris 1996; Tolbert et al.1982).Early recordings showed that bushy cells fire only one ortwo action potentials at the onset, whereas stellate cells firetonically in response to a suprathreshold depolarizing currentpulse (Fujino and Oertel 2001; Oertel 1983; Schwarz and Puil1997; Wu and Oertel 1984). It has been reported that althoughall bushy cells fire transiently when they are depolarized,