Computational model for the bushy cell of the cochlear nucleus
Introduction
The cochlear nucleus contains the second-order neurons of the auditory system. Several cell types can be distinguished morphologically and physiologically. Studies using slices [4] or isolated cells [3] have shown that the bushy cell fires just one or two action potentials (APs) at the onset of a depolarizing current step while the response of the cochlear nucleus stellate cell is characterized by a regular series of APs. The bushy cells are thought to preserve the precision of temporal information so that it can be used to process interaural timing differences. The latter is important for sound localization [1]. Bushy cells receive a strong excitatory input from a few auditory nerve axons directly on the soma in the form of an endbulb of Held. The bushy cell membrane also possesses potassium (K+) channels with different activation thresholds: low-threshold (GKLT) and high-threshold channels [3]. The principal cell of the medial nucleus of the trapezoid body (MNTB) exhibits response properties similar to those of the bushy cell [2], [8].
The present study used a computational model (adapted from Rothman et al. [7]) to investigate the roles played by the low- and high-threshold K+ channels in determining the characteristic responses of the bushy cell and the MNTB cell: (1) onset discharges to a step depolarizing current (in vitro; e.g. [4], [8]; (2) the ability to entrain to high-rate current pulse trains (in vitro; e.g. [6], [8]; (3) the ability to show precise temporal encoding, i.e., phase locking at high frequencies (in vivo; e.g. [9]).
The present study evaluated the following hypotheses: (1) The GKLT channel of the bushy cell, which is partially activated at the resting potential, shortens the cell membrane time constant; (2) The GKLT channel of the bushy cell underlies the onset discharge behavior of the cell to current-step stimulation; (3) The GKHT channel (fast delayed rectifier Kv3.1) of the bushy cell rapidly repolarizes APs (i.e., sharpens APs) and allows the cell to fire at high rates; (4) The combined actions of GKLT and GKHT, in conjunction with the sodium channel (GNa), contribute to optimize the bushy cell's precise temporal-encoding ability such as entrainment to high-rate pulse train stimulation and accurate phase locking to high-frequency acoustic stimulation.
Section snippets
Methods
The model was implemented using Neurokit of GENESIS V2.1 running on an SGI Onyx computer with time steps. The model was a one-compartment representation of a bushy cell and included GKLT [3], GKHT (Kv3.1 [5]) and GNa channels plus a leakage channel and membrane capacitance (Fig. 1 and Table 1). The model was adapted from Rothman et al. [7] and the temperature was set to 22°C to match the condition of the Wang et al. [8] data. The present model had the following modifications from those of
Results
The model was tested with current step injections. For comparison, the response of a mouse MNTB neuron is shown in Fig. 2, reprinted with permission from Wang et al. [8]. In the control (Fig. 2A), the MNTB cell fired one or a few APs at the beginning of the current step. The AP of the cell was narrow and there was after-hyperpolarization reaching below the resting potential at the trailing phase of the AP. When 100 nM dendrotoxin (DTX) was applied, which is expected to block the low-threshold
Discussion
The main finding of the present study is that a one-compartment model of the cochlear nucleus bushy cell, that incorporates several K+ and Na+ channels, reproduced salient features of experimental observations of the time-encoding auditory cells, i.e., the cochlear nucleus bushy and MNTB cells. The reproduced response features include narrow APs, onset discharges to current steps and entrainment to high-rate pulse-train stimulation. The model also reproduced response alterations experimentally
Acknowledgements
This study was supported in part by grants No. DC00360 and DC00025 from NIDCD, NIH.
Duck O. Kim is currently Professor, Neuroscience Program, Otolaryngology/Surgery, Biomedical Engineering, University of Connecticut Health Center, Farmington, CT. In 1968, he received B.S. degree in Electronic Engineering from Seoul National University, Seoul, Korea, and in 1972, D.Sc. degree in Biomedical Engineering from Washington University, St. Louis, MO. He worked as a member of staff, Bell Laboratories, Murray Hill, NJ, and as a faculty member at Washington University, St. Louis, MO, and
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Cited by (1)
Duck O. Kim is currently Professor, Neuroscience Program, Otolaryngology/Surgery, Biomedical Engineering, University of Connecticut Health Center, Farmington, CT. In 1968, he received B.S. degree in Electronic Engineering from Seoul National University, Seoul, Korea, and in 1972, D.Sc. degree in Biomedical Engineering from Washington University, St. Louis, MO. He worked as a member of staff, Bell Laboratories, Murray Hill, NJ, and as a faculty member at Washington University, St. Louis, MO, and University of Wisconsin, Madison, WI, before taking the present position. His research interests include computational neuroscience, neurophysiology and neuroanatomy, particularly as applied to the auditory system.
William R. D'Angelo received his B.S. in electrical engineering from Worcester Polytechnic Institute in 1990 and M.S. in biomedical engineering from Boston University in 1992. From there he entered the U.S. Air Force as a biomedical engineer. Working in the Air Force Research Laboratory, he designed and tested virtual auditory displays for military applications. In 1997, he left the Air Force and is now a Ph.D. candidate in the Neuroscience Program at the University of Connecticut Health Center. His current research involves the use of multi-electrode arrays and study of the bineural hearing system.