Differential Expression of Three Distinct Potassium Currents in the Ventral Cochlear Nucleus

2003 ◽  
Vol 89 (6) ◽  
pp. 3070-3082 ◽  
Author(s):  
Jason S. Rothman ◽  
Paul B. Manis
Keyword(s):  
Differential Expression ◽  
Cochlear Nucleus ◽  
Nerve Fibers ◽  
Delayed Rectifier ◽  
High Threshold ◽  
Type I ◽  
Acoustic Environment ◽  
Ventral Cochlear Nucleus ◽  
Wide Range ◽  
Slope Factor

In the ventral cochlear nucleus (VCN), neurons transform information from auditory nerve fibers into a set of parallel ascending pathways, each emphasizing different aspects of the acoustic environment. Previous studies have shown that VCN neurons differ in their intrinsic electrical properties, including the K+ currents they express. In this study, we examine these K+ currents in more detail using whole cell voltage-clamp techniques on isolated VCN cells from adult guinea pigs at 22°C. Our results show a differential expression of three distinct K+ currents. Whereas some VCN cells express only a high-threshold delayed-rectifier-like current ( IHT), others express IHT in combination with a fast inactivating current ( IA) and/or a slow-inactivating low-threshold current ( ILT). IHT, ILT, and IA, were partially blocked by 1 mM 4-aminopyridine. In contrast, only ILT was blocked by 10–100 nM dendrotoxin-I. A surprising finding was the wide range of levels of ILT, suggesting ILT is expressed as a continuum across cell types rather than modally in a particular cell type. IA, on the other hand, appears to be expressed only in cells that show little or no ILT, the Type I cells. Boltzmann analysis shows IHT activates with 164 ± 12 (SE) nS peak conductance, -14.3 ± 0.7 mV half-activation, and 7.0 ± 0.5 mV slope factor. Similar analysis shows ILT activates with 171 ± 22 nS peak conductance, -47.4 ± 1.0 mV half-activation, and 5.8 ± 0.3 mV slope factor.

Convergence of auditory nerve fibers onto bushy cells in the ventral cochlear nucleus: implications of a computational model

1993 ◽  
Vol 70 (6) ◽  
pp. 2562-2583 ◽  
Author(s):  
J. S. Rothman ◽  
E. D. Young ◽  
P. B. Manis
Keyword(s):  
Cochlear Nucleus ◽  
Auditory Nerve ◽  
Full Range ◽  
Nerve Fibers ◽  
Membrane Properties ◽  
Delayed Rectifier ◽  
Current Clamp ◽  
Synaptic Inputs ◽  
Ventral Cochlear Nucleus ◽  
Bushy Cells

1. Convergence of auditory nerve (AN) fibers onto bushy cells of the ventral cochlear nucleus (VCN) was investigated with a model that describes the electrical membrane properties of these cells. The model consists of a single compartment, representing the soma, and includes three voltage-sensitive ion channels (fast sodium, delayed-rectifier-like potassium, and low-threshold potassium). These three channels have characteristics derived from voltage clamp data of VCN bushy cells. The model also contains a leakage channel, membrane capacitance, and synaptic inputs. The model accurately reproduces the membrane rectification seen in current clamp studies of bushy cells, as well as their unique current clamp responses. 2. In this study, the number and synaptic strength of excitatory AN inputs to the model were varied to investigate the relationship between input convergence parameters and response characteristics. From 1 to 20 excitatory synaptic inputs were applied through channels in parallel with the voltage-gated channels. Each synapse was driven by an independent AN spike train; spike arrivals produced brief (approximately 0.5 ms) conductance increases. The number (NS) and conductance (AE) of these inputs were systematically varied. The input spike trains were generated as a renewal point process that accurately models characteristics of AN fibers (refractoriness, adaptation, onset latency, irregularity of discharge, and phase locking). Adaptation characteristics of both high and low spontaneous rate (SR) AN fibers were simulated. 3. As NS and AE vary over the ranges 1–20 and 3–80 nS, respectively, the full range of response types seen in VCN bushy cells are produced by the model, with AN inputs typical of high-SR AN fibers. These include primarylike (PL), primarylike-with-notch (Pri-N), and onset-L (On-L). In addition, Onset responses, whose association with bushy cells in uncertain, and “dip” responses, which are not seen in the VCN, are produced. Dip responses occur with large NS and/or AE, and are due to depolarization block. When the AN inputs have the adaptation characteristics of low-SR AN fibers, PL--but not Pri-N or On-L responses--are produced. This suggests that neurons showing Pri-N and On-L responses must receive high-SR AN inputs. 4. The regularity of discharge of the model is compared with that of VCN bushy cells, using a measure derived from the mean and standard deviation of interspike intervals. Regularity is an important constraint on the model because the regularity of VCN bushy cells is the same as that of their AN inputs.(ABSTRACT TRUNCATED AT 400 WORDS)

Frequency extent of two-tone facilitation in onset units in the ventral cochlear nucleus

1996 ◽  
Vol 75 (1) ◽  
pp. 380-395 ◽  
Author(s):  
D. Jiang ◽  
A. R. Palmer ◽  
I. M. Winter
Keyword(s):  
Cochlear Nucleus ◽  
Auditory Nerve ◽  
Low Frequency ◽  
Nerve Fibers ◽  
Inhibitory Input ◽  
Ventral Cochlear Nucleus ◽  
Narrow Region ◽  
Morphological Studies ◽  
Wide Range ◽  
Auditory Nerve Fibers

1. The frequency threshold curves (FTCs) of 91 single units in the cochlear nucleus of the anesthetized guinea pig were measured using a conventional single-tone paradigm and a two-tone paradigm designed to elucidate the frequency extent of two-tone facilitation in onset units (On). Units were classified according to existing classification schemes into primary-like (n = 3), chopper (n = 23), and three onset groups: OnI (n = 12), OnC (n = 29), and OnL (n = 24). Histological reconstructions show onset units to be widely distributed within the ventral cochlear nucleus in a manner generally consistent with its tonotopic organization. 2. The FTCs of onset units differed in their minimum thresholds, the steepness of their high- and low-frequency cutoffs, and their sharpness of tuning as quantified by the quality factor at 10 dB (Q10dB) above best frequency (BF) threshold values. There was considerable overlap in the sharpness of tuning between onset units and auditory nerve fibers, as indicated by the distribution of Q10dB values in the octave around 10 kHz: onset units had Q10dB values of 3.56 +/- 1.38 (SD), compared with 6.3 +/- 2.48 for auditory nerve fibers. The tuning of chopper units was similar to that of auditory nerve fibers (5.52 +/- 1.46). 3. Seventy-five percent of onset units showed some degree of facilitation (a threshold reduction) when their FTCs were measured in the presence of BF tones 4 dB below BF threshold. The frequency extent of such facilitation was variable, with a maximum of 6 octaves around the BF. In extreme cases facilitation could be measured when the BF tone was as low as 30 dB below BF threshold. 4. In 17% of onset units, suppressive effects were evident, as shown by noncontiguous frequency regions of facilitation. These suppressive effects might be a reflection either of suppression in the auditory nerve input or of a direct inhibitory input to the onset units. The strength of this effect suggests that inhibition is a likely explanation, consistent with the finding in previous morphological studies of profuse synapses with pleomorphic vesicles on multipolar cells. 5. FTCs of chopper and primary-like units measured in the presence of BF tones showed little facilitation. The facilitation that was observed in chopper units was confined to a narrow region around BF and disappeared when the facilitatory tone was lowered to 4 dB below BF threshold. 6. These data support the hypothesis that onset units, but not chopper or primary-like units, receive excitatory inputs from auditory nerve fibers with a wide range of BFs. However, the frequency range of facilitation and the magnitude of the threshold facilitation varied from unit to unit, suggesting that the off-BF inputs from auditory nerve fibers are not evenly distributed or equally effective in all units.

Potassium Currents in Octopus Cells of the Mammalian Cochlear Nucleus

2001 ◽  
Vol 86 (5) ◽  
pp. 2299-2311 ◽  
Author(s):  
Ramazan Bal ◽  
Donata Oertel
Keyword(s):  
Cochlear Nucleus ◽  
Nerve Fibers ◽  
Resting Potential ◽  
Equilibrium Potential ◽  
Repetitive Firing ◽  
High Threshold ◽  
Low Input ◽  
Wide Range ◽  
Maximal Activation ◽  
Low Threshold

Octopus cells in the posteroventral cochlear nucleus (PVCN) of mammals are biophysically specialized to detect coincident firing in the population of auditory nerve fibers that provide their synaptic input and to convey its occurrence with temporal precision. The precision in the timing of action potentials depends on the low input resistance (∼6 MΩ) of octopus cells at the resting potential that makes voltage changes rapid (τ ∼ 200 μs). It is the activation of voltage-dependent conductances that endows octopus cells with low input resistances and prevents repetitive firing in response to depolarization. These conductances have been examined under whole cell voltage clamp. The present study reveals the properties of two conductances that mediate currents whose reversal at or near the equilibrium potential for K+ over a wide range of extracellular K+ concentrations identifies them as K+ currents. One rapidly inactivating conductance, g KL, had a threshold of activation at −70 mV, rose steeply as a function of depolarization with half-maximal activation at −45 ± 6 mV (mean ± SD), and was fully activated at 0 mV. The low-threshold K+ current ( I KL) was largely blocked by α-dendrotoxin (α-DTX) and partially blocked by DTX-K and tityustoxin, indicating that this current was mediated through potassium channels of the Kv1 (also known as shakeror KCNA) family. The maximum low-threshold K+conductance ( g KL) was large, 514 ± 135 nS. Blocking I KL with α-DTX revealed a second K+ current with a higher threshold ( I KH) that was largely blocked by 20 mM tetraethylammonium (TEA). The more slowly inactivating conductance, g KH, had a threshold for activation at −40 mV, reached half-maximal activation at −16 ± 5 mV, and was fully activated at +30 mV. The maximum high-threshold conductance, g KH, was on average 116 ± 27 nS. The present experiments show that it is not the biophysical and pharmacological properties but the magnitude of the K+ conductances that make octopus cells unusual. At the resting potential, −62 mV, g KLcontributes ∼42 nS to the resting conductance and mediates a resting K+ current of 1 nA. The resting outward K+ current is balanced by an inward current through the hyperpolarization-activated conductance, g h, that has been described previously.

Responses of ventral cochlear nucleus onset and chopper units as a function of signal bandwidth

1996 ◽  
Vol 75 (2) ◽  
pp. 780-794 ◽  
Author(s):  
A. R. Palmer ◽  
D. Jiang ◽  
D. H. Marshall
Keyword(s):  
Spectral Density ◽  
Cochlear Nucleus ◽  
Narrow Range ◽  
Discharge Rate ◽  
Nerve Fibers ◽  
Low Noise ◽  
Dorsal Cochlear Nucleus ◽  
Ventral Cochlear Nucleus ◽  
Wide Range ◽  
Response Area

1. The responses of units in the ventral cochlear nucleus in anesthetized guinea pigs have been measured to best-frequency tones, noise bands geometrically centered around the unit best frequency, and noise bands asymmetrically positioned around the best frequency. 2. Each unit isolated was characterized using peristimulus time histograms (PSTHs) to best-frequency tones at 20 and 50 dB suprathreshold, frequency-intensity response areas and rate-versus-level functions in response to best-frequency tones and wideband noise. The data reported here are derived from full analyses of 5 chopper units and 17 onset units. The onsets were divided into onset-I (OnI), onset-L (OnL), and onset-C (OnC) by the criteria described by Winter and Palmer: the PSTHs of OnI units show only an onset response, OnL units respond with a single spike at onset followed by a low level of sustained activity, and OnC units have PSTHs with one to four onset peaks and low levels of sustained discharge. 3. In response to geometrically centered noise bands of constant spectral density, the discharge of chopper units and one OnI unit increased over a relatively narrow range of bandwidths, corresponding to the equivalent rectangular bandwidth calculated from their response area, and then became constant. In contrast, OnL and OnC units showed increases in discharge rate with noise bandwidth over very wide ranges of bandwidth. The growth of the discharge rate with noise bandwidth was approximately linear on double logarithmic axes and therefore could be described by a power function with an exponent of 0.37. This relation held even for noise levels near threshold. 4. When noise bands with constant spectral density (at the input to the earphone) were presented with one edge fixed at the unit's best frequency, the discharge rate of most chopper units and the one OnI unit increased over a narrow range of bandwidths and then became constant. This pattern was observed irrespective of whether the second edge of the noise was progressively increased above, or decreased below, the best frequency. For two of the chopper units, in which lateral inhibitory sidebands could be demonstrated, increasing the noise bandwidth led first to increases and then to decreases in the discharge rate as the noise energy impinged upon the sideband. The chopper units act like energy detectors with a filter corresponding to their single tone response area, but, for some units, with the addition of inhibitory sidebands. 5. For the OnL and OnC units, increasing the noise bandwidth above or below best frequency caused progressive increases in the discharge rate over wide ranges of bandwidth. These increases occurred even for low noise spectral densities. The growth in discharge rate for these onset units was well fitted at all spectral density levels by power functions: one above best frequency and one below. At levels of the noise 40 dB above the unit threshold, the point at which the discharge rate reached 90% of its maximum was, on average, about 2 octaves below best frequency and 1 octave above. For some onset units, changes in the discharge rate were seen as the noise bandwidth was varied over about 14 kHz, which is about one-third of the total frequency hearing range of the guinea pig. 6. The data for onset units is consistent with the hypothesis that onset units in the ventral cochlear nucleus achieve their precision in the temporal domain by integration of the inputs from auditory nerve fibers with a wide range of best frequencies. The range of frequency over which onset units integrate frequency matches that of the inhibitory input to dorsal cochlear nucleus neurons, suggesting a possible role as an inhibitory interneuron.

The Roles Potassium Currents Play in Regulating the Electrical Activity of Ventral Cochlear Nucleus Neurons

2003 ◽  
Vol 89 (6) ◽  
pp. 3097-3113 ◽  
Author(s):  
Jason S. Rothman ◽  
Paul B. Manis
Keyword(s):  
Cochlear Nucleus ◽  
Auditory Nerve ◽  
Threshold Current ◽  
Repetitive Firing ◽  
Resting Membrane Potential ◽  
Type I ◽  
Type Ii Cells ◽  
Type Ii ◽  
Ventral Cochlear Nucleus ◽  
Discharge Patterns

Using kinetic data from three different K+ currents in acutely isolated neurons, a single electrical compartment representing the soma of a ventral cochlear nucleus (VCN) neuron was created. The K+ currents include a fast transient current ( IA), a slow-inactivating low-threshold current ( ILT), and a noninactivating high-threshold current ( IHT). The model also includes a fast-inactivating Na+ current, a hyperpolarization-activated cation current ( Ih), and 1–50 auditory nerve synapses. With this model, the role IA, ILT, and IHT play in shaping the discharge patterns of VCN cells is explored. Simulation results indicate that IHT mainly functions to repolarize the membrane during an action potential, and IA functions to modulate the rate of repetitive firing. ILT is found to be responsible for the phasic discharge pattern observed in Type II cells (bushy cells). However, by adjusting the strength of ILT, both phasic and regular discharge patterns are observed, demonstrating that a critical level of ILT is necessary to produce the Type II response. Simulated Type II cells have a significantly faster membrane time constant in comparison to Type I cells (stellate cells) and are therefore better suited to preserve temporal information in their auditory nerve inputs by acting as precise coincidence detectors and having a short refractory period. Finally, we demonstrate that modulation of Ih, which changes the resting membrane potential, is a more effective means of modulating the activation level of ILT than simply modulating ILT itself. This result may explain why ILT and Ih are often coexpressed throughout the nervous system.

Encoding timing and intensity in the ventral cochlear nucleus of the cat

1986 ◽  
Vol 56 (2) ◽  
pp. 261-286 ◽  
Author(s):  
W. S. Rhode ◽  
P. H. Smith
Keyword(s):  
Firing Rate ◽  
Cochlear Nucleus ◽  
Auditory Nerve ◽  
Cell Types ◽  
Nerve Fibers ◽  
Frequency Selectivity ◽  
Firing Rates ◽  
Ventral Cochlear Nucleus ◽  
Auditory Nerve Fibers ◽  
Different Cell Types

Physiological response properties of neurons in the ventral cochlear nucleus have a variety of features that are substantially different from the stereotypical auditory nerve responses that serve as the principal source of activation for these neurons. These emergent features are the result of the varying distribution of auditory nerve inputs on the soma and dendrites of the various cell types within the nucleus; the intrinsic membrane characteristics of the various cell types causing different responses to the same input in different cell types; and secondary excitatory and inhibitory inputs to different cell types. Well-isolated units were recorded with high-impedance glass microelectrodes, both intracellularly and extracellularly. Units were characterized by their temporal response to short tones, rate vs. intensity relation, and response areas. The principal response patterns were onset, chopper, and primary-like. Onset units are characterized by a well-timed first spike in response to tones at the characteristic frequency. For frequencies less than 1 kHz, onset units can entrain to the stimulus frequency with greater precision than their auditory nerve inputs. This implies that onset units receive converging inputs from a number of auditory nerve fibers. Onset units are divided into three subcategories, OC, OL, and OI. OC units have extraordinarily wide dynamic ranges and low-frequency selectivity. Some are capable of sustaining firing rates of 800 spikes/s at high intensities. They have the smallest standard deviation and coefficient of variation of the first spike latency of any cells in the cochlear nuclei. OC units are candidates for encoding intensity. OI and OL units differ from OC units in that they have dynamic ranges and frequency selectivity ranges much like those of auditory nerve fibers. They differ from one another in their steady-state firing rates; OI units fire mainly at the onset of a tone. OI units also differ from OL units in that they prefer frequency sweeps in the low to high direction. Primary-like-with-notch (PLN) units also respond to tones with a well-timed first spike. They differ from onset cells in that the onset peak is not always as precise as the spontaneous rate is higher. A comparison of spontaneous firing rate and saturation firing rate of PLN units with auditory nerve fibers suggest that PLN units receive one to four auditory nerve fiber inputs. Chopper units fire in a sustained regular manner when they are excited by sound.(ABSTRACT TRUNCATED AT 400 WORDS)

Kinetic Analyses of Three Distinct Potassium Conductances in Ventral Cochlear Nucleus Neurons

2003 ◽  
Vol 89 (6) ◽  
pp. 3083-3096 ◽  
Author(s):  
Jason S. Rothman ◽  
Paul B. Manis
Keyword(s):  
Fourth Order ◽  
Cochlear Nucleus ◽  
Cell Types ◽  
High Threshold ◽  
Ventral Cochlear Nucleus ◽  
First Order Kinetics ◽  
Recovery From Inactivation ◽  
Potassium Conductances ◽  
Voltage Dependent ◽  
Discharge Patterns

Neurons in the ventral cochlear nucleus (VCN) express three distinct K+ currents that differ in their voltage and time dependence, and in their inactivation behavior. In the present study, we quantitatively analyze the voltage-dependent kinetics of these three currents to gain further insight into how they regulate the discharge patterns of VCN neurons and to provide supporting data for the identification of their channel components. We find the transient A-type K+ current ( IA) exhibits fourth-order activation kinetics ( a4), and inactivates with one or two time constants. A second inactivation rate (leading to an a4 bc kinetic description) is required to explain its recovery from inactivation. The dendrotoxin-sensitive low-threshold K+ current ( ILT) also activates with fourth-order kinetics ( w4) but shows slower, incomplete inactivation. The high-threshold K+ current ( IHT) appears to consist of two kinetically distinct components ( n2 + p). The first component activates ∼10 mV positive to the second and has second-order kinetics. The second component activates with first-order kinetics. These two components also contribute to two kinetically distinct currents upon deactivation. The kinetic behavior of IHT was indistinguishable amongst cell types, suggesting the current is mediated by the same K+ channels amongst VCN neurons. Together these results provide a basis for more realistic modeling of VCN neurons, and provide clues regarding the molecular basis of the three K+ currents.

The Functional Role of Excitatory and Inhibitory Interactions in Chopper Cells of the Anteroventral Cochlear Nucleus

1994 ◽  
Vol 6 (6) ◽  
pp. 1127-1140 ◽  
Author(s):  
Ying-Cheng Lai ◽  
Raimond L. Winslow ◽  
Murray B. Sachs
Keyword(s):  
Cochlear Nucleus ◽  
Auditory Nerve ◽  
Dendritic Tree ◽  
Nerve Fibers ◽  
High Threshold ◽  
Spontaneous Rate ◽  
Anteroventral Cochlear Nucleus ◽  
Rate Versus ◽  
High Stimulus ◽  
Auditory Nerve Fibers

Chopper cells in the anteroventral cochlear nucleus of the cat maintain a robust rate-place representation of vowel spectra over a broad range of stimulus levels. This representation resembles that of low threshold, high spontaneous rate primary auditory nerve fibers at low stimulus levels, and that of high threshold, low spontaneous rate auditory-nerve fibers at high stimulus levels. This has led to the hypothesis that chopper cells in the anteroventral cochlear nucleus selectively process inputs from different spontaneous rate populations of primary auditory-nerve fibers at different stimulus levels. We present a computational model, making use of shunting inhibition, for how this level dependent processing may be performed within the chopper cell dendritic tree. We show that this model (1) implements level-dependent selective processing, (2) reproduces detailed features of real chopper cell post-stimulus-time histograms, and (3) reproduces nonmonotonic rate versus level functions in response to single tones measured.

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