Evidence of a sensory processing unit in the mammalian macula.

We cut serial sections through the medial part of the rat vestibular macula for transmission electron microscopic (TEM) examination, computer-assisted 3-D reconstruction, and compartmental modeling. The ultrastructural research showed that many primary vestibular neurons have an unmyelinated segment, often branched, that extends between the heminode (putative site of the spike initiation zone) and the expanded terminal(s) (calyx, calyces). These segments, termed the neuron branches, and the calyces frequently have spine-like processes of various dimensions with bouton endings that morphologically are afferent, efferent, or reciprocal to other macular neural elements. The major questions posed by this study were whether small details of morphology, such as the size and location of neuronal processes or synapses, could influence the output of a vestibular afferent, and whether a knowledge of morphological details could guide the selection of values for simulation parameters. The conclusions from our simulations are (1) values of 5.0 k omega cm2 for membrane resistivity and 1.0 nS for synaptic conductance yield simulations that best match published physiological results; (2) process morphology has little effect on orthodromic spread of depolarization from the head (bouton) to the spike initiation zone (SIZ); (3) process morphology has no effect on antidromic spread of depolarization to the process head; (4) synapses do not sum linearly; (5) synapses are electrically close to the SIZ; and (6) all whole-cell simulations should be run with an active SIZ.

Compartmental modeling of rat macular primary afferents from three-dimensional reconstructions of transmission electron micrographs of serial sections.

1. We cut serial sections through the medial part of the rat vestibular macula for transmission electron microscopic (TEM) examination, computer-assisted three-dimensional (3-D) reconstruction, and compartmental modeling. The ultrastructural research showed that many primary vestibular neurons have an unmyelinated segment, often branched, that extends between the heminode [putative site of the spike initiation zone (SIZ)] and the expanded terminal(s) (calyx, calyces). These segments, termed the neuron branches, and the calyces frequently have spinelike processes of various dimensions that morphologically are afferent, efferent, or reciprocal to other macular neural elements. The purpose of this research was to determine whether morphometric data obtained ultrastructurally were essential to compartmental models [i.e., they influenced action potential (AP) generation, latency, or amplitude] or whether afferent parts could be collapsed into more simple units without markedly affecting results. We used the compartmental modeling program NEURON for this research. 2. In the first set of simulations we studied the relative importance of small variations in process morphology on distant depolarization. A process was placed midway along an isolated piece of a passive neuron branch. The dimensions of the four processes corresponded to actual processes in the serial sections. A synapse, placed on the head of each process, was activated and depolarization was recorded at the end of the neuron branch. When we used 5 nS synaptic conductance, depolarization varied by 3 mV. In a systematic study over a representative range of stem dimensions, depolarization varied by 15.7 mV. Smaller conductances produced smaller effects. Increasing membrane resistivity from 5,000 to 50,000 omega cm2 had no significant effect. 3. In a second series of simulations, using whole primary afferents, we examined the combined effects of process location and afferent morphology on depolarization magnitude and latency, and the effect of activating synapses individually or simultaneously. Process location affects peak latency and voltage recorded at the heminode. A synapse on a calyceal process produced < or = 8% more depolarization and a 23% increase in peak latency compared with a synapse on a process of a neuron branch. For whole primary afferents, depolarization decreased 40% between simulations of the smallest and largest afferents. Simulations in which membrane resistivity and synaptic conductance were varied while afferent geometry was kept constant indicated that use of 5,000 omega cm2 and 1.0 nS produced results that best fit electrophysiological findings. Synaptic inputs activated simultaneously did not sum linearly at the heminode. Total depolarization was approximately 14% less than a simple summation of responses of synapses activated one at a time.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation and recovery from adaptation of the auditory nerve neurophonic (ANN) using long duration tones.

The time course of the interaction between adaptation and the recovery from adaptation of the auditory nerve neurophonic (ANN) responses was examined. The interaction between the process of recovery and the adaptation process of long probe tones which follow a masker, the so called whole tone recovery, was determined for the ANN response for different silent intervals between masker offset and probe onset. The auditory nerve neurophonic (ANN) reflects the ensemble response of phase-locked firing in single auditory nerve fibers to sustained signals. Consequently, neural response properties such as adaptation and recovery from adaptation of these coherent, time-locked responses can be studied. Recovery from adaptation was determined by recording the response of a 290 ms duration probe tone following a 100 ms masker tone, equal in frequency to the probe, ranging from -5 to 20 dB relative to the probe amplitude. Two different time patterns of the whole tone recovery were observed. If short silent intervals and/or loud maskers were used, the time course of the probe tone can be described as an exponential increase in amplitude toward a steady state expressed by the equation: A(tp) = Ass-Yr e(-tp/tau Rr)-Ys e(-tp/tau Rs) ('ascending exponential'). For longer silent intervals and/or fainter maskers, the time course of the probe tone can be described by an exponential decrease expressed by the equation: A(tp) = Yr e(-tp/tau Rr) +Ys e(-tp/tau Rs) +A(ss) ('declining exponential').

Adaptation and recovery from adaptation in single fiber responses of the cat auditory nerve.

This study examined the time course of adaptation and recovery from adaptation of single auditory-nerve fiber responses. The conditions studied were: (1) adaptation response using low level, 800 Hz or characteristic frequency (CF) stimuli; and (2) onset recovery and whole tone response recovery of a probe tone following a masker of equal frequency with variable silent intervals between the masker offset and probe onset. Single unit responses to 290 ms long, 800 Hz or CF tones presented at 10-30 dB SL were recorded from the auditory nerve of the cat. Adaptation properties were determined and fit to the equation: A(tp) = Yre(-tp/tau Rr) + Yse(-tp/tau Rs) + Ass. Recovery from adaptation was determined by recording the response of a probe tone following a 100-ms masker tone equal in frequency to the probe, and with amplitudes ranging from 20- to 30-dB relative to the probe amplitude. Both the onset recovery and the whole tone recovery were determined for the single unit responses. The onset data were analyzed and fit to either the equation: A (delta xt,tp) = Ass - Yre(-tp/tau Rr) - Yse(- delta t/tau Rs) or A (delta t,tp) = Ass - Yre(- delta t/tau R). The whole tone response showed two distinctive time patterns that could be fit to either an adaptation equation or to the two-time-constant recovery equation, depending on the relative amplitude of the masker and the length of the silent interval between masker offset and probe onset. The results of this study indicate that single fiber time constants are comparable to those measured in previous studies using the auditory-nerve neurophonic (ANN). Likewise, the pattern of recovery of the whole tone response for single fiber responses is comparable to the ANN. Possible sites and mechanisms for adaptation and recovery from adaptation taking into account recent data from electrical stimulation studies and receptor channel morphology and kinetics are discussed.

Time course of adaptation and recovery from adaptation in the cat auditory-nerve neurophonic.

The auditory-nerve neurophonic (ANN) reflects the ensemble response of phase-locked firing in single auditory-nerve fibers to sustained signals. Consequently, neural response properties such as adaptation and recovery from adaptation can be observed. In this study, ANN responses to 800-Hz, 100-ms tones presented at 10-30-dB SL were recorded using bipolar platinum-iridium electrodes placed on the auditory nerve of the cat. The cat ANN adaptation properties were determined and fit to the equation: A(tp) = Yre(-tp/tau Ar) + Yse(-tp/tau As) + Ass. The rapid time constant of adaptation (tau Ar) was invariant across stimulus level, with a mean value of 4.8 (+/- 2.1) ms. The short-term time constant (tau As) decreased approximately 21 ms for each 10-dB increase in probe amplitude. The mean tau As was 116 ms at 10 dB SL, 83.2 ms at 20 dB SL, and 73.5 ms at 30 dB SL. The ANN recovery from adaptation data was analyzed and fit to the equation: A(delta t) = Amax - Yre(-delta t/tau Rr) - Yse(-delta t/tau Rs). Here, tau Rr, the rapid time constant of recovery, and tau Rs, the short-term time constant, were independent of masker intensity in the studied range, with values of 16.2(+/- 9.8) and 125(+/- 50.1) ms, respectively. The results of this study indicate that ANN time constants are comparable to those measured for single units and that the adaptation behavior of phase-locked and nonphase-locked activity appears to be similar.

Selectively eliminating cochlear microphonic contamination from the frequency-following response.

The frequency-following response (FFR) is the scalp recorded response to low frequency stimuli. As an electrophysiological method for determining auditory threshold, it has application in both clinical and research settings. However, the response is often contaminated with the cochlear microphonic (CM), reflecting the response of outer hair cells, rather than neural generators (i.e., auditory nerve, cochlear nucleus, superior olivary nucleus, inferior colliculus, etc.). The FFR needs to be a purely neural response to establish its clinical and experimental usefulness. The methods applied to date have failed to accomplish this. The present study demonstrates a method of deriving a pure neural response by subtracting a forward masked FFR, which contains only CM, from an unmasked FFR. To confirm that the residual response after forward masking is solely CM, one needs to record two forward masked responses with opposite phase probe stimuli. When the responses are added they will sum to zero only if the residual response with forward masking is pure CM. This study demonstrates that the traditional method for removing CM from FFR, by simple summation of unmasked responses recorded with stimuli of opposite phase, does not accurately reflect the amplitude or frequency of the FFR, while the proposed method provides an accurate assessment of the FFR amplitude free of CM contamination.

Peripheral neurotoxicity testing by pairs of stimuli.

At the present time the best electrophysiological test of peripheral nerve function for purposes of evaluating neurotoxicity in humans is the analysis of the response to pairs of stimuli. This test is a more sensitive measure of axonal conduction deficit than is the single-action potential of standard clinical technique. While not as sensitive a measure as a train of stimuli at any given frequency of stimulation, the paired stimulus technique has the following advantages. The interpretation of responses to trains of impulses can be made inaccurate by alternate blocking. Under such conditions the pairs response will already have shown impaired conduction, The method is sufficiently sensitive that the second response of the pair is decreased in normals. Thus the test will show any neurotoxic impairment which is additive to such normal physiological decrement. The method has already been reported in the literature as being sensitive to a number of different peripheral and central neuropathies in humans, including segmental demyelination and axonal degeneration. The equipment required is often already in the standard clinical facility, or can be added at reasonable cost. Stimulation with pairs is more acceptable to the subject since it is not as painful as presentation of stimulus trains.

Effects of acute nerve compression on conduction of impulse trains of increasing frequency.

The acute effect of localized nerve compression has been detected electrophysiologically in isolated rat tail nerve by utilizing a special stimulus pattern, a STIF (Stimulus Train of Increasing Frequency), which shows the highest frequency that the most sensitive axons in a compound potential can transmit through the compressed region. The same method also detected recovery after release of compression. Overlap of waveforms at high frequencies of stimulation required special techniques to permit unequivocal measurements. The best endpoint at which to detect the acute nerve compression in these experiments was found to be that frequency at which only a few fibers were blocked. The method was also effective when part of the nerve was completely blocked by the compression, and was more sensitive than measure of change in latency of a single response.