- Email: [email protected]
Auditory Physiology: Listening with K+ Channels
Current Biology, Vol. 13, R767–R769, September 30, 2003, ©2003 Elsevier Science Ltd. All rights reserved. DOI 10.1016/j.cub.2003.09.018
Auditory Physiology: Listening with K+ Channels Ruth Anne Eatock
New data on neurons in the auditory brainstem have been incorporated into simulations which show how ion channels and synaptic inputs may be combined to produce diverse sound-evoked responses.
Neuroscientists examine the biophysical properties of ion channels with the goal of understanding how they shape neuronal output during sensory, motor or cognitive tasks, but the connection between studies of ion channel properties and neuronal encoding is often weak. In the cochlear nucleus complex, recognizable neuronal morphologies have allowed investigators to link ion channel and synaptic properties with specific sound-evoked responses. In three recent papers [1–3], Jason Rothman and Paul Manis report new results on the ion channels of ventral cochlear nucleus neurons and simulations incorporating the new data which reproduce well-known features of the neurons’ responses to sounds. Primary auditory afferent neurons bifurcate as they enter the ventral cochlear nucleus (Figure 1A), sending an ascending branch into the anteroventral part and a descending branch through the posteroventral part to the dorsal cochlear nucleus (reviewed in [4]). Each afferent forms excitatory glutamatergic synapses on multiple secondary neurons, which fall into distinct morphological classes that project to different higherlevel targets (reviewed in [5]). The important cell classes in the ventral cochlear nucleus include bushy cells, which have extensive secondary apical dendrites emanating from a short thick primary dendrite, and stellate (multipolar) cells, which have multiple long dendrites (Figure 1B). Most primary auditory afferents form one or two very large endings (‘endbulbs of Held’; Figure 1A) on the cell bodies of spherical bushy cells; several slightly smaller endings (‘modified endbulbs’) on the cell bodies and proximal dendrites of globular bushy cells; and multiple en passant or bouton synapses on various neurons. The different neuronal classes of the cochlear nuclei produce distinctive sound-evoked responses. In response to short-duration pure-frequency sounds (tone bursts), primary auditory afferents produce an initial vigorous response which declines to a steady level [6]. The tone burst response patterns of cochlear nucleus neurons [7,8] include: ‘primary-like’ responses, similar to those of the afferents; ‘primary-like with notch’ responses, in which a brief refractory period follows the peak response; ‘onset-L’ responses, in which a narrow peak is followed by low sustained firing; and ‘chopper’ Department of Otolaryngology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. E-mail: [email protected]
Dispatch
responses, in which spikes occur at regular intervals unrelated to their frequency tuning. Bushy cells tend to make primary-like or onset-L responses, often with very precise timing, while stellate cells tend to make chopper responses (Figure 1C) [9,10]. These response differences arise in part from the striking differences in afferent synaptic contacts. The large endbulbs of Held seem designed to transmit incoming action potentials rapidly — that is, to make primary-like responses with high temporal fidelity. The multiple endbulbs and bouton synapses on globular bushy cells are well suited to coincidence detection, a process that sharpens the timing of responses [11]. The location of bouton endings on the dendrites of certain stellate cells may degrade temporal processing through electrotonic decay to the spike initiating zone [12]. But the neurons’ intrinsic electrophysiological properties are also likely to shape their sound-evoked activity, as shown by their voltage responses to injected currents (Figure 1D) [13–15]. Bushy cells respond to depolarizing current steps with one-to-several spikes at the onset — known as the Type II response — reminiscent of their onset and primary-like responses to tone bursts, while stellate cells respond to current steps with trains of regularly spaced spikes — the Type I response — similar to their chopper tone-burst responses. Bushy cells have low input resistances at resting potential, which confer short membrane time constants that favor temporal processing. Manis and colleagues [1,2,16] have used whole-cell patch clamp recording to characterize the voltage dependence and kinetics of voltage-gated currents responsible for the intrinsic differences that lead to Type I and Type II responses (Figure 1E). All neurons express a ‘high-threshold-activating’ current, IHT, an outwardly rectifying K+ current which activates above the resting potential. This current may be carried by KCNC (Kv3) subunits, some of which are expressed at a high level in auditory brainstem neurons [17]. The low input resistances of Type II cells arise from the additional expression of currents that are partly activated at resting potential: the ‘low-threshold-activating’ current, ILT, an outwardly rectifying K+ current that is blocked by dendrotoxin, and Ih, an inwardly rectifying current carried by both K+ and Na+ ions. The molecule composition of the channels mediating ILT is not known, but these channels may be widely expressed in the auditory system; similar dendrotoxin-sensitive, low-threshold K+ currents are expressed by other central auditory neurons that may be specialized for rapid signaling [18–20]. ILT is most prominent in Type II neurons, but it is also expressed to varying amounts in about half of the Type I neurons. Rothman and Manis [3] assessed the impact of individual voltage-gated conductances on current- and sound-evoked responses by representing cells that produce Type I, Type II and intermediate responses
Dispatch R768
Figure 1. Structure and function in the cochlear nuclei. (A) A slice through the mammalian cochlear nuclei. A labelled auditory nerve fiber enters and bifurcates, sending one process through the anteroventral cochlear nucleus (AVCN) and the other branch across the posteroventral cochlear nucleus (PVCN) to the dorsal cochlear nucleus (DCN). The fibers form modified endbulbs of Held on globular bushy cells and bouton endings on globular bushy cells and stellate (multipolar) cells, terminating in large endbulbs (inset) on spherical bushy cells. (B–E) In addition to their different afferent contacts, bushy cells (top) and stellate cells (bottom) have distinct: (B) morphologies; (C) spike responses to 30 ms tone bursts, shown as peri-stimulus time histograms; (D) intracellular voltage responses to 100 ms current steps; and (E) whole-cell current responses to families of 100-ms voltage steps. According to Rothman and Manis [3], the difference in the voltage responses to current steps (D) can be explained by the presence in bushy cells of a critical amount of lowvoltage-activating current, ILT, and the difference in tone-burst responses (C) can be explained by the different combinations of voltage-gated currents and afferent synaptic inputs. (Adapted, with permission, from [1,4,7,9,10,15].)
with Hodgkin–Huxley models for specific combinations of conductances and synaptic inputs. The simulations yielded a rich trove of testable insights into the known properties of bushy and stellate neurons, including their phase-locking and entrainment capabilities and their responses to current steps and tone bursts. On the question of what differentiates cells that produce Type I and Type II responses to current steps, the model and data agree that the Type II response requires a critical density of ILT channels. At lower densities, neurons make responses that vary in a graduated manner with the ILT channel density, from Type I responses to mixed, level-dependent responses (single spikes to small current steps and multiple but not sustained spikes to large current steps). To simulate tone burst responses, Rothman and Manis [3] drove the Hodgkin–Huxley models with model auditory nerve input arriving via different synaptic arrangements. The simulated response patterns were found to match observations in several ways. Cells with large ILT — the model bushy cells — respond with primary-like responses or onset-L responses, depending on the nature of the synaptic input. One-to-several supra-threshold inputs, representing endbulbs, generate primary-like or primary-like-with-notch responses. Many identical sub-threshold inputs, as may occur on globular bushy cells, evoke onset-L responses. This arrangement is ideal for sharpening timing through coincidence detection: multiple inputs can overcome
the low gain of the neuron (conferred by its low input resistance), but only if they coincide, because the short membrane time constant prevents temporal integration over long intervals. Large numbers of sub-threshold synaptic inputs onto cells with no ILT — model stellate cells — evoke chopper responses. The high input resistances of stellate cells at resting potential confer long membrane time and space constants which allow summation of excitatory post-synaptic potentials from many synapses, producing a steady depolarization. This in turn evokes a train of regularly spaced spikes, as expected from the stellate cell’s Type I voltage response to a depolarizing current step. The modeling by Rothman and Manis [3] shows how strikingly different response patterns can emerge from simple variations in ion channels and synaptic inputs. While this has been an underlying assumption of studies on auditory brainstem neurons since the pioneering observations of Oertel [13], the present study stands out for its integration of detailed biophysical characterizations with previous morphological and sound-evoked response data in an extensive modeling effort. Such simulations are necessary when dealing with multiple interacting processes, such as voltagegated currents that feed back on each other. On the other hand, the more detailed the models, the more forgiving they can be of underlying errors; as noted by Rothman and Manis [3], previous models based on less
Current Biology R769
accurate characterizations of the ion channels also succeeded in predicting certain response properties. Despite its relative sophistication, the modeling by Rothman and Manis [3] also involved deliberate simplifications, the effects of which are unexplored. These include: the experimental blocking of Ca2+ and Ca2+-activated currents, which are important in setting firing patterns in some neurons; the use of generic rather than actual values for the voltage-gated Na+ current, which may critically affect spike timing; the placement of all synaptic inputs on the cell body, although some are dendritic. Nevertheless, these examples from the ventral cochlear nucleus show that bridging the chasm between ion-channel and higher-level neurophysiology can reward us with insights into the significance of ion channel diversity in central neurons. References 1. Rothman, J.S., and Manis, P.B. (2003). Differential expression of three distinct potassium currents in the ventral cochlear nucleus. J. Neurophysiol. 89, 3070-3082. 2. Rothman, J.S., and Manis, P.B. (2003). Kinetic analyses of three distinct potassium conductances in ventral cochlear nucleus neurons. J. Neurophysiol. 89, 3083-3096. 3. Rothman J.S., and Manis P.B. (2003). The roles potassium currents play in regulating the electrical activity of ventral cochlear nucleus neurons. J. Neurophysiol. 89, 3097-3113. 4. Ryugo D.K., and Parks, T.N. (2003). Primary innervation of the avian and mammalian cochlear nucleus. Brain Res. Bull. 60, 435-456. 5. Cant, N.B., and Benson, C.G. (2003). Parallel auditory pathways: projection patterns of the different neuronal populations in the dorsal and ventral cochlear nuclei. Brain Res. Bull. 60, 457-474. 6. Kiang, N.Y.S., Watanabe ,T., Thomas, E.C., and Clark, L.F. (1965). Discharge patterns of single fibers in the cat’s auditory nerve. Cambridge, M.I.T. Press. 7. Pfeiffer, R.R. (1966). Classification of response patterns of spike discharges for units in the cochlear nucleus, Tone-burst stimulation. Exp. Brain Res. 1, 220-235. 8. Blackburn, C.C. and Sachs, M.B. (1989). Classification of unit types in the anteroventral cochlear nucleus, PST histograms and regularity analysis. J. Neurophysiol. 62,1303-1329. 9. Smith, P.H., and Rhode, W.S. (1987). Characterization of HRPlabeled globular bushy cells in the cat anteroventral cochlear nucleus. J. Comp. Neurol. 266, 360-375. 10. Smith, P.H., and Rhode W.S. (1989). Structural and functional properties distinguish two types of multipolar cells in the ventral cochlear nucleus. J. Comp. Neurol. 282, 595-616. 11. Joris, P.X., Carney, L.H., Smith, P.H., and Yin, T.C. (1994). Enhancement of neural synchronization in the anteroventral cochlear nucleus. I. Responses to tones at the characteristic frequency. J. Neurophysiol. 71, 1022-1036. 12. White, J.A., Young, E.D., and Manis, P.B. (1994). The electrotonic structure of regular-spiking neurons in the ventral cochlear nucleus may determine their response properties. J. Neurophysiol. 71, 17741786. 13. Oertel, D. (1983). Synaptic responses and electrical properties of cells in brain slices of the mouse anteroventral cochlear nucleus. J. Neurosci. 3, 2043-2053. 14. Wu, S.H., and Oertel, D. (1984). Intracellular injection with horseradish peroxidase of physiologically characterized stellate and bushy cells in slices of mouse anteroventral cochlear nucleus. J. Neurosci. 4, 1577-1588. 15. Francis, H.W., and Manis, P.B. (2000). Effects of deafferentation on the electrophysiology of ventral cochlear nucleus neurons. Hear. Res. 149, 91-105. 16. Manis, P.B., and Marx, S.O. (1991). Outward currents in isolated ventral cochlear nucleus neurons. J. Neurosci. 11, 2865-2880. 17. Li , W., Kaczmarek, L.K., and Perney, T.M. (2001). Localization of two high-threshold potassium channel subunits in the rat central auditory system. J. Comp. Neurol. 437, 196-218. 18. Brew H.M., and Forsythe, I.D. (1995). Two voltage-dependent K+ conductances with complementary functions in postsynaptic integration at a central auditory synapse. J. Neurosci. 15, 8011-8022. 19. Rathouz, M., and Trussell, L. (1998). Characterization of outward currents in neurons of the avian nucleus magnocellularis. J. Neurophysiol. 80, 2824-2835. 20. Bal, R., and Oertel, D. (2001). Potassium currents in octopus cells of the mammalian cochlear nucleus. J. Neurophysiol. 86, 22992311.
Auditory Physiology: Listening with K+ Channels Ruth Anne Eatock
New data on neurons in the auditory brainstem have been incorporated into simulations which show how ion channels and synaptic inputs may be combined to produce diverse sound-evoked responses.
Neuroscientists examine the biophysical properties of ion channels with the goal of understanding how they shape neuronal output during sensory, motor or cognitive tasks, but the connection between studies of ion channel properties and neuronal encoding is often weak. In the cochlear nucleus complex, recognizable neuronal morphologies have allowed investigators to link ion channel and synaptic properties with specific sound-evoked responses. In three recent papers [1–3], Jason Rothman and Paul Manis report new results on the ion channels of ventral cochlear nucleus neurons and simulations incorporating the new data which reproduce well-known features of the neurons’ responses to sounds. Primary auditory afferent neurons bifurcate as they enter the ventral cochlear nucleus (Figure 1A), sending an ascending branch into the anteroventral part and a descending branch through the posteroventral part to the dorsal cochlear nucleus (reviewed in [4]). Each afferent forms excitatory glutamatergic synapses on multiple secondary neurons, which fall into distinct morphological classes that project to different higherlevel targets (reviewed in [5]). The important cell classes in the ventral cochlear nucleus include bushy cells, which have extensive secondary apical dendrites emanating from a short thick primary dendrite, and stellate (multipolar) cells, which have multiple long dendrites (Figure 1B). Most primary auditory afferents form one or two very large endings (‘endbulbs of Held’; Figure 1A) on the cell bodies of spherical bushy cells; several slightly smaller endings (‘modified endbulbs’) on the cell bodies and proximal dendrites of globular bushy cells; and multiple en passant or bouton synapses on various neurons. The different neuronal classes of the cochlear nuclei produce distinctive sound-evoked responses. In response to short-duration pure-frequency sounds (tone bursts), primary auditory afferents produce an initial vigorous response which declines to a steady level [6]. The tone burst response patterns of cochlear nucleus neurons [7,8] include: ‘primary-like’ responses, similar to those of the afferents; ‘primary-like with notch’ responses, in which a brief refractory period follows the peak response; ‘onset-L’ responses, in which a narrow peak is followed by low sustained firing; and ‘chopper’ Department of Otolaryngology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. E-mail: [email protected]
Dispatch
responses, in which spikes occur at regular intervals unrelated to their frequency tuning. Bushy cells tend to make primary-like or onset-L responses, often with very precise timing, while stellate cells tend to make chopper responses (Figure 1C) [9,10]. These response differences arise in part from the striking differences in afferent synaptic contacts. The large endbulbs of Held seem designed to transmit incoming action potentials rapidly — that is, to make primary-like responses with high temporal fidelity. The multiple endbulbs and bouton synapses on globular bushy cells are well suited to coincidence detection, a process that sharpens the timing of responses [11]. The location of bouton endings on the dendrites of certain stellate cells may degrade temporal processing through electrotonic decay to the spike initiating zone [12]. But the neurons’ intrinsic electrophysiological properties are also likely to shape their sound-evoked activity, as shown by their voltage responses to injected currents (Figure 1D) [13–15]. Bushy cells respond to depolarizing current steps with one-to-several spikes at the onset — known as the Type II response — reminiscent of their onset and primary-like responses to tone bursts, while stellate cells respond to current steps with trains of regularly spaced spikes — the Type I response — similar to their chopper tone-burst responses. Bushy cells have low input resistances at resting potential, which confer short membrane time constants that favor temporal processing. Manis and colleagues [1,2,16] have used whole-cell patch clamp recording to characterize the voltage dependence and kinetics of voltage-gated currents responsible for the intrinsic differences that lead to Type I and Type II responses (Figure 1E). All neurons express a ‘high-threshold-activating’ current, IHT, an outwardly rectifying K+ current which activates above the resting potential. This current may be carried by KCNC (Kv3) subunits, some of which are expressed at a high level in auditory brainstem neurons [17]. The low input resistances of Type II cells arise from the additional expression of currents that are partly activated at resting potential: the ‘low-threshold-activating’ current, ILT, an outwardly rectifying K+ current that is blocked by dendrotoxin, and Ih, an inwardly rectifying current carried by both K+ and Na+ ions. The molecule composition of the channels mediating ILT is not known, but these channels may be widely expressed in the auditory system; similar dendrotoxin-sensitive, low-threshold K+ currents are expressed by other central auditory neurons that may be specialized for rapid signaling [18–20]. ILT is most prominent in Type II neurons, but it is also expressed to varying amounts in about half of the Type I neurons. Rothman and Manis [3] assessed the impact of individual voltage-gated conductances on current- and sound-evoked responses by representing cells that produce Type I, Type II and intermediate responses
Dispatch R768
Figure 1. Structure and function in the cochlear nuclei. (A) A slice through the mammalian cochlear nuclei. A labelled auditory nerve fiber enters and bifurcates, sending one process through the anteroventral cochlear nucleus (AVCN) and the other branch across the posteroventral cochlear nucleus (PVCN) to the dorsal cochlear nucleus (DCN). The fibers form modified endbulbs of Held on globular bushy cells and bouton endings on globular bushy cells and stellate (multipolar) cells, terminating in large endbulbs (inset) on spherical bushy cells. (B–E) In addition to their different afferent contacts, bushy cells (top) and stellate cells (bottom) have distinct: (B) morphologies; (C) spike responses to 30 ms tone bursts, shown as peri-stimulus time histograms; (D) intracellular voltage responses to 100 ms current steps; and (E) whole-cell current responses to families of 100-ms voltage steps. According to Rothman and Manis [3], the difference in the voltage responses to current steps (D) can be explained by the presence in bushy cells of a critical amount of lowvoltage-activating current, ILT, and the difference in tone-burst responses (C) can be explained by the different combinations of voltage-gated currents and afferent synaptic inputs. (Adapted, with permission, from [1,4,7,9,10,15].)
with Hodgkin–Huxley models for specific combinations of conductances and synaptic inputs. The simulations yielded a rich trove of testable insights into the known properties of bushy and stellate neurons, including their phase-locking and entrainment capabilities and their responses to current steps and tone bursts. On the question of what differentiates cells that produce Type I and Type II responses to current steps, the model and data agree that the Type II response requires a critical density of ILT channels. At lower densities, neurons make responses that vary in a graduated manner with the ILT channel density, from Type I responses to mixed, level-dependent responses (single spikes to small current steps and multiple but not sustained spikes to large current steps). To simulate tone burst responses, Rothman and Manis [3] drove the Hodgkin–Huxley models with model auditory nerve input arriving via different synaptic arrangements. The simulated response patterns were found to match observations in several ways. Cells with large ILT — the model bushy cells — respond with primary-like responses or onset-L responses, depending on the nature of the synaptic input. One-to-several supra-threshold inputs, representing endbulbs, generate primary-like or primary-like-with-notch responses. Many identical sub-threshold inputs, as may occur on globular bushy cells, evoke onset-L responses. This arrangement is ideal for sharpening timing through coincidence detection: multiple inputs can overcome
the low gain of the neuron (conferred by its low input resistance), but only if they coincide, because the short membrane time constant prevents temporal integration over long intervals. Large numbers of sub-threshold synaptic inputs onto cells with no ILT — model stellate cells — evoke chopper responses. The high input resistances of stellate cells at resting potential confer long membrane time and space constants which allow summation of excitatory post-synaptic potentials from many synapses, producing a steady depolarization. This in turn evokes a train of regularly spaced spikes, as expected from the stellate cell’s Type I voltage response to a depolarizing current step. The modeling by Rothman and Manis [3] shows how strikingly different response patterns can emerge from simple variations in ion channels and synaptic inputs. While this has been an underlying assumption of studies on auditory brainstem neurons since the pioneering observations of Oertel [13], the present study stands out for its integration of detailed biophysical characterizations with previous morphological and sound-evoked response data in an extensive modeling effort. Such simulations are necessary when dealing with multiple interacting processes, such as voltagegated currents that feed back on each other. On the other hand, the more detailed the models, the more forgiving they can be of underlying errors; as noted by Rothman and Manis [3], previous models based on less
Current Biology R769
accurate characterizations of the ion channels also succeeded in predicting certain response properties. Despite its relative sophistication, the modeling by Rothman and Manis [3] also involved deliberate simplifications, the effects of which are unexplored. These include: the experimental blocking of Ca2+ and Ca2+-activated currents, which are important in setting firing patterns in some neurons; the use of generic rather than actual values for the voltage-gated Na+ current, which may critically affect spike timing; the placement of all synaptic inputs on the cell body, although some are dendritic. Nevertheless, these examples from the ventral cochlear nucleus show that bridging the chasm between ion-channel and higher-level neurophysiology can reward us with insights into the significance of ion channel diversity in central neurons. References 1. Rothman, J.S., and Manis, P.B. (2003). Differential expression of three distinct potassium currents in the ventral cochlear nucleus. J. Neurophysiol. 89, 3070-3082. 2. Rothman, J.S., and Manis, P.B. (2003). Kinetic analyses of three distinct potassium conductances in ventral cochlear nucleus neurons. J. Neurophysiol. 89, 3083-3096. 3. Rothman J.S., and Manis P.B. (2003). The roles potassium currents play in regulating the electrical activity of ventral cochlear nucleus neurons. J. Neurophysiol. 89, 3097-3113. 4. Ryugo D.K., and Parks, T.N. (2003). Primary innervation of the avian and mammalian cochlear nucleus. Brain Res. Bull. 60, 435-456. 5. Cant, N.B., and Benson, C.G. (2003). Parallel auditory pathways: projection patterns of the different neuronal populations in the dorsal and ventral cochlear nuclei. Brain Res. Bull. 60, 457-474. 6. Kiang, N.Y.S., Watanabe ,T., Thomas, E.C., and Clark, L.F. (1965). Discharge patterns of single fibers in the cat’s auditory nerve. Cambridge, M.I.T. Press. 7. Pfeiffer, R.R. (1966). Classification of response patterns of spike discharges for units in the cochlear nucleus, Tone-burst stimulation. Exp. Brain Res. 1, 220-235. 8. Blackburn, C.C. and Sachs, M.B. (1989). Classification of unit types in the anteroventral cochlear nucleus, PST histograms and regularity analysis. J. Neurophysiol. 62,1303-1329. 9. Smith, P.H., and Rhode, W.S. (1987). Characterization of HRPlabeled globular bushy cells in the cat anteroventral cochlear nucleus. J. Comp. Neurol. 266, 360-375. 10. Smith, P.H., and Rhode W.S. (1989). Structural and functional properties distinguish two types of multipolar cells in the ventral cochlear nucleus. J. Comp. Neurol. 282, 595-616. 11. Joris, P.X., Carney, L.H., Smith, P.H., and Yin, T.C. (1994). Enhancement of neural synchronization in the anteroventral cochlear nucleus. I. Responses to tones at the characteristic frequency. J. Neurophysiol. 71, 1022-1036. 12. White, J.A., Young, E.D., and Manis, P.B. (1994). The electrotonic structure of regular-spiking neurons in the ventral cochlear nucleus may determine their response properties. J. Neurophysiol. 71, 17741786. 13. Oertel, D. (1983). Synaptic responses and electrical properties of cells in brain slices of the mouse anteroventral cochlear nucleus. J. Neurosci. 3, 2043-2053. 14. Wu, S.H., and Oertel, D. (1984). Intracellular injection with horseradish peroxidase of physiologically characterized stellate and bushy cells in slices of mouse anteroventral cochlear nucleus. J. Neurosci. 4, 1577-1588. 15. Francis, H.W., and Manis, P.B. (2000). Effects of deafferentation on the electrophysiology of ventral cochlear nucleus neurons. Hear. Res. 149, 91-105. 16. Manis, P.B., and Marx, S.O. (1991). Outward currents in isolated ventral cochlear nucleus neurons. J. Neurosci. 11, 2865-2880. 17. Li , W., Kaczmarek, L.K., and Perney, T.M. (2001). Localization of two high-threshold potassium channel subunits in the rat central auditory system. J. Comp. Neurol. 437, 196-218. 18. Brew H.M., and Forsythe, I.D. (1995). Two voltage-dependent K+ conductances with complementary functions in postsynaptic integration at a central auditory synapse. J. Neurosci. 15, 8011-8022. 19. Rathouz, M., and Trussell, L. (1998). Characterization of outward currents in neurons of the avian nucleus magnocellularis. J. Neurophysiol. 80, 2824-2835. 20. Bal, R., and Oertel, D. (2001). Potassium currents in octopus cells of the mammalian cochlear nucleus. J. Neurophysiol. 86, 22992311.