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Biomedical subjects

A L Nuttall

Publications and source records attributed to A L Nuttall.

At least 127 records · Page 7Linked to original sources
PubMed1987

Velocity of red blood cell flow in capillaries of the guinea pig cochlea.

Velocities of red blood cells (RBCs) in the lateral wall of the cochlea were determined in the anesthetized guinea pig from direct optical microscopic observations. Mean flow velocity of the blood was measured by timing the passage of a fluorescently-labeled subpopulation of RBCs across a measured capillary length. The optical observations were achieved using an intravital microscope equipped for epifluorescence and the measurements were derived from video images acquired with an image intensified television camera. In the third turn of the cochlea the velocity of RBCs differed significantly between two major classes of capillaries. The mean velocity in spiral ligament vessels was 0.12 mm/s while stria vascularis flow was slower (0.08 mm/s). In a typical animal, the range of velocities among different vessels of the ligament was 0.09-0.18 mm/s while it was 0.03-0.10 mm/s for stria vascularis vessels. Corresponding to this velocity difference, the apparent mean vessel diameters for the two types of vessels also differed. Spiral ligament capillaries were 9.3 micron while strial capillaries were 12.2 micron in diameter. Comparison of flow velocity in different turns of the cochlea indicated that the distribution of blood velocity throughout the cochlea lateral wall is constant.

Animals↗
PubMed1987

Laser Doppler measurements of cochlear blood flow during loud sound exposure in the guinea pig.

This investigation examined the effects of loud sound of different frequencies and intensities on cochlear blood flow as measured by the laser Doppler flowmeter. Cochlear blood flow was measured in anesthetized guinea pigs during a 1 h exposure to either a 2, 4, or 12 kHz pure tone or high-pass noise (10-40 kHz) at 90, 103, or 110 dB SPL. Cochlear function was assessed using the compound action potential audiogram before and after exposure. There was no change in blood flow in the second turn with a 2, 4, or 12 kHz tone but there was a significant (P less than 0.05) decline in flow in the first cochlear turn at the end of either the 12 kHz tone or high-pass noise exposure at 103 and 110 dB SPL. There were elevations in the thresholds of the cochlear compound action potential after all but the 90 dB exposures to 12 kHz or high-pass noise. No such changes were observed in blood flow or electrophysiology in control animals. These findings demonstrate that there is a small but significant decline in cochlear blood flow with high intensity sound exposure. However, the relationship between this change in blood flow and the development of cochlear damage is unclear.

Animals↗
PubMed1987

Effects of carbon monoxide on cochlear electrophysiology and blood flow.

The belief that the cochlea is particularly vulnerable to a reduction in oxygen availability comes predominantly from studies reporting the disruption of electrophysiological measures, such as the compound action potential, endocochlear potential, inner hair cell intracellular potentials or afferent nerve fiber responses by asphyxiation. Because hypoxia has frequently been suggested as an underlying mechanism by which many ototoxic agents produce injury, and because such agents are not likely to completely disrupt oxygen delivery, we investigated the effects of graded hypoxia (using doses of carbon monoxide) on cochlear blood flow, the compound action potential (CAP) and the cochlear microphonic (CM). High doses of carbon monoxide injected intra-peritoneally yielded reversible loss of the CAP sensitivity for high frequency tone bursts, the extent of which was dose dependent. The loss was observed first at the highest frequency tested (50 kHz) and as carboxyhemoglobin levels increased, contiguous lower frequencies were influenced. Recovery progressed from low to high frequencies as carboxyhemoglobin levels declined. Carbon monoxide administration also produced a dose dependent elevation in the cochlear blood flow measured by a laser Doppler flow monitor. The data suggest that carbon monoxide administration disrupts cochlear function only under extremely severe exposure conditions. An elevation in cochlear blood flow may well serve as a protective mechanism which maintains cochlear function in the face of declining blood oxygen carrying capacity and delivery. While the site of action of carbon monoxide in the cochlea is uncertain, the data clearly indicate that elements involved in the generation of the CAP for high frequency tones are particularly vulnerable.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Cryoprobe-induced apical lesions in the chinchilla. I. Morphological effects of lesioning parameters.

To create experimental lesions localized to the low frequency region of the organ of Corti, a cryoprobe was applied to the apical area of 37 cochleas from 26 adult chinchillas. Twenty cochleas were exposed to single applications of a cryoprobe for 2.5, 3.0 and 3.5 min; 17 cochleas were exposed to two applications of 1.5, 2.0 and 3.0 min each with about a 3 min interval between applications. Cryoprobe tip temperature rose from about -140 degrees C when placed on the apex to about -80 degrees C after a continuous 3.5 min application. Survival time after lesioning was from 2 to 75 days, with most being 12 days or less. All cochleas except one sustained regions of damage characterized by complete absence of the organ of Corti and by missing hair cells indicated by extensive scarring. Inner hair cells were less susceptible to damage than were outer hair cells. Well-defined lesions which were continuous over the apical organ of Corti were found in some cochleas exposed to single probe applications, but such applications more often resulted in lesions which had areas of less damage. Of the various application protocols used, two applications of 1.5 min each, with an interval to allow the tissue to warm, most consistently produced severe and discrete apical lesions. In 9 of 13 cochleas exposed to two 1.5 min probe applications, such lesions extended about 35% or less of the distance from the apex. In most cochleas, regardless of the severity of the apical lesion, the pattern of hair cell rows and stereocilia configuration appeared normal in the basal 40-50% of the organ of Corti.

Animals↗
PubMed1987

Cryoprobe-induced apical lesions in the chinchilla. II. Effects on behavioral auditory thresholds.

Lesions of the hair cells in the cochlear apex were produced by a miniature cryoprobe and changes in behavioral auditory thresholds were measured. Monauralized adult chinchillas were behaviorally trained using operant procedures to produce pure-tone audiograms at frequencies from 63 Hz to 40 kHz. Following collection of baseline thresholds, the apical and middle turns of the experimental ear were visualized through a hole drilled in the bulla and a copper cryoprobe that had been cooled in liquid nitrogen was placed on the apical turn of the cochlea. Post-lesion threshold shifts from two subjects showed a flat loss of approximately 20 dB restricted to frequencies below either 710 Hz or 1 kHz; thresholds were normal at higher frequencies. The cytocochleograms, prepared from the ears following completion of threshold testing, show an almost complete loss of both inner and outer hair cells in the apical-most 20% of the cochlea with an abrupt transition region to areas of normal-looking hair cell populations. The relationship between the frequencies at which hearing was impaired and the location of missing hair cells along the basilar membrane is in agreement with the frequency-place map for the chinchilla of Eldredge et al. [(1981) J. Acoust. Soc. Am. 69, 1091-1095]. The magnitude of the loss, however, is less than might be expected based on comparison with threshold shifts produced by similar pathology in the basal turns.

Acoustic Stimulation↗
PubMed1986

Trimethyltin ototoxicity: evidence for a cochlear site of injury.

The environmental contaminant, trimethyltin (TMT), produces a profound elevation in tone intensity necessary to inhibit the acoustic startle reflex in laboratory animals which recovers over a prolonged period except at very high frequencies. The recovery that is observed does not begin until 3 to 5 weeks after a single acute administration depending upon dosage. As opposed to the very temporary threshold shifts by the salicylates and loop diuretics or the permanent and progressive ototoxicity resulting from aminoglycoside antibiotics the time course for recovery of acoustic startle reflex inhibition after TMT appears to be an anomaly for a chemical ototoxicant. In terms of the duration of loss only, this pattern appears similar to that sometimes observed after noise exposure. The current investigation replicates the finding that recovery of acoustic startle reflex inhibition after TMT is frequency related in that only the highest frequency impairment appears to be permanent. While this frequency dependence suggests a cochlear locus of injury, both the known neurotoxic effects of TMT and the time course of the behavioral impairment suggest a more central locus of injury. Compound action potential and cochlear microphonic recordings made from the round window in the current study confirm a preferential high frequency effect of TMT and demonstrate a significant cochlear component to the ototoxic effects of this agent.

Action Potentials↗
PubMed1985

The effects of cochlear hypothermia on compound action potential tuning.

The effects of lowered cochlear temperature on eighth-nerve tuning were assessed by using forward masking of whole nerve action potential (AP) responses to generate AP tuning curves (APTCs) at cochlear temperatures ranging from 38.5 degrees to 30 degrees C for probe frequencies from 8 to 36 kHz. The data indicate that subnormal cochlear temperatures result in: broadened APTCs for probe frequencies above 10 kHz which are interpreted as resulting from reduced hair-cell frequency selectivity, lowered or more sensitive APTC tips where tone-burst thresholds are unchanged, and raised or less sensitive tips where thresholds to tone bursts were elevated. Increased tip sensitivity is explained in terms of enhanced eighth-nerve adaptation which occurred during hypothermia. Experiments directly addressing adaptation were performed, in which the masker-probe interval (delta t) was systematically lengthened. The normalized AP decrement versus delta t functions indicate an enhancement of both the amount and duration of adaptation during hypothermia. Functions relating the growth of response to the masker (AP decrement versus masker intensity functions) were reduced at low temperatures.

Acclimatization↗
PubMed1985

Influence of direct current on dc receptor potentials from cochlear inner hair cells in the guinea pig.

Inner hair cell responses to sound were monitored while direct current was applied across the membranous labyrinth in the first turn of the guinea pig cochlea. The current injection electrodes were positioned in the scala vestibuli and on the round window membrane. Positive and negative current (less than 100 microA) caused changes in the sound-evoked dc receptor potentials which were dependent on the sound frequency and intensity. The frequencies most affected by this extracellular current were those comprising the "tip" portion of the inner hair cell frequency tuning characteristic (FTC). The influence of current increased with increasing frequency. Positive current increased the amount of dc receptor potential for the affected frequencies while negative current decreased the potential. Current-induced changes (on a percentage basis) were greater for low intensity sounds and the negative current direction. These frequency specific changes are evidenced as a loss in sensitivity for the tip area of the FTC and a downward shift of the inner hair cell characteristic frequency. Larger current levels (greater than 160 microA) cause more complex changes including unrecoverable loss of cell performance. In separate experiments positive and negative currents (less than 1.1 microA) were injected into the inner hair cell from the recording electrode during simultaneous measurement of the sound-evoked dc receptor potential. This condition caused a shift in IHC sensitivity that was independent of sound frequency and intensity. Positive current decreased the sensitivity of the level of the cell while negative current increased the responses. The effect of current level on sound-evoked dc receptor potential was nonlinear, as comparatively greater increases in cell response were observed for negative than decreases for positive current. The intracellular current injection results are accounted for by the mechano-resistive model of hair cell transduction, where nonlinear responses with current level may reflect outward rectification. Response changes induced by extracellular current are evidence of current effects on both inner and outer hair cells. The frequency and intensity dependences are hypothesized to represent voltage mediated control of inner hair cell response by the outer hair cells.

Action Potentials↗
PubMed1985

High-synchrony cochlear compound action potentials evoked by rising frequency-swept tone bursts.

The auditory compound action potential (CAP) represents synchronous VIIIth nerve activity. Clicks or impulses have been used in the past to produce this synchrony under the assumption that the wide spectral spread inherent in transient signals will activate a large portion of the cochlear partition. However, the observation that only auditory nerve units tuned above 3 kHz contribute to synchronous activity in the N1P1 complex of the CAP [Dolan et al., J. Acoust. Soc. Am. 73, 580-591 (1983)] suggests that temporal delays imposed by the traveling wave result in an asynchronous pattern of VIIIth nerve activation. In order to determine if units tuned below 3 kHz could be recruited into the CAP response, the present study uses tone bursts of exponentially rising frequency to hypothetically activate synchronous discharges of VIIIth nerve fibers along the length of the cochlear partition. The equations defining the frequency sweeps are calculated to be the inverse of the delay-line characteristics of the guinea pig cochlear partition. The resultant sweeps theoretically cause a constant phase displacement of a large portion of the cochlear partition at one time. Compound action potentials recorded in response to the rising frequency sweeps were compared to CAPs evoked by corresponding falling frequency sweeps and clicks. Analysis of the CAP waveforms showed narrower N1 widths and larger N1 and P1 amplitudes for rising sweeps when compared to falling sweeps. This is consistent with the hypothesis of increased synchrony. A further test of the hypothesis was made by using high-pass masking noise to evaluate the contributions of discrete cochlear locations to the CAP ("derived" CAP). Latency functions of the derived CAPs for clicks and falling frequency sweeps showed progressive increases in latency as the cutoff frequency of the high-pass filter was lowered. The latency of the derived CAP for these stimulus conditions reflects traveling wave delays [Aran and Cazals, "Electrocochleography: Animal studies," in Evoked Electrical Activity in The Auditory Nervous System (Academic, New York, 1978)]. In contrast, derived CAPs obtained from rising sweeps showed no change in latency for any cutoff frequencies, indicating a constant delay of response for fibers with different characteristic frequencies (CFs). These results support the theoretical premise underlying the derivation of the rising sweep: Spectral energy with the appropriate temporal organization, dictated by basilar membrane traveling wave properties, will increase CAP synchrony.

Acoustic Stimulation↗
PubMed1984

Dynamic aspects of guinea pig inner hair cell receptor potentials with transient asphyxia.

DC and AC receptor potentials of cochlear inner hair cells in response to tone bursts of various frequencies and intensities were continuously measured during and following periods of transient asphyxia. The effects of asphyxia were most pronounced for low sound pressure level (SPL) acoustic stimuli near the characteristic frequency (CF) of the inner hair cell, leading to vulnerability of the 'tip' of the cell's frequency tuning curve (FTC). The resulting changes in the shape of the FTC are, first, a reduction in tip criterion sensitivity of 10-20 dB without significant loss in sharpness of tuning. Later, when the full effect of 30-45 s asphyxia occurs, tip sensitivity loss between 30 and 65 dB is accompanied by greatly broadened tuning and a shift downward in frequency of the CF by greater than 1/4 octave. The CF shift is due to a progressive loss of high frequency sensitivity. The linear segment of the input-output (intensity) function, plotted as log DC receptor potential versus SPL (at the original CF), becomes longer during the early phase asphyxia, and the slope of the segment declines by 50%. At high SPLs, for all frequencies, the time course of the receptor potential change was similar in shape to that exhibited by the endocochlear potential (EP). In particular, for high sound levels, the recovery of response matches the EP while for low level tip frequency sounds recovery is protracted. No difference between the decline of the AC and DC receptor potentials at CF was observed. Inner hair cell resting membrane potential (Em) hyperpolarized during asphyxia by 2-6 mV, correlating with the change in EP according to a ratio of 1/10 (Em/EP).

Animals↗
PubMed1984

Efferent control of cochlear inner hair cell responses in the guinea-pig.

The efferent crossed olivocochlear bundle (c.o.c.b.) was electrically stimulated during intracellular recordings from cochlear inner hair cells in anaesthetized guinea-pigs. The effect of c.o.c.b. stimulation was to decrease the magnitude of the inner hair cell depolarizing component (d.c.) and alternating component (a.c.) receptor potentials evoked by tone bursts at the characteristic frequency. At low sound pressure levels, the decrease in receptor potentials caused by c.o.c.b. stimulation was equivalent to decreasing the sound intensity by 9-24 dB. C.o.c.b. stimulation usually had a similar effect on the compound action potential of the auditory nerve. The change in inner hair cell membrane resistance during moderate-level sound was measured for sound alone and when sound was accompanied by c.o.c.b. stimulation. Sound alone produced a greater membrane resistance change than sound with c.o.c.b. stimulation, in proportion to the d.c. receptor potential during the same conditions. The time course of the c.o.c.b. effect was slow, with 50-250 ms required for a full effect and for recovery. The effects of varying the frequency and voltage of electrical stimulation were similar for the d.c. receptor potential and for the compound action potential. For sounds of high level and for frequencies well below the characteristic frequency, c.o.c.b. stimulation was less effective in reducing receptor potentials. Frequency tuning curves for the d.c. receptor potential taken during intervals of continuous c.o.c.b. stimulation showed decreases in sensitivity primarily in the tip segment of the tuning curve. When no sound stimulus was present, the resting membrane potential was relatively unaltered during c.o.c.b. stimulation. The resting membrane resistance did not change during c.o.c.b. stimulation. Since the c.o.c.b. innervates mainly the outer hair cells, these results strongly suggest that changes in outer hair cell activity can influence the receptor potentials of inner hair cells and thus alter the transmission of acoustic responses to the central nervous system.

Animals↗
PubMed1983

Intracellular recordings from cochlear inner hair cells: effects of stimulation of the crossed olivocochlear efferents.

Intracellular recordings were obtained from inner hair cells located in the lower basal turn of the guinea pig cochlea. At low sound pressure levels the inner hair cells were highly frequency selective, producing receptor potentials only in response to sound frequencies between about 16 and 24 kilohertz. Electrical stimulation of efferent nerves in the crossed olivocochlear bundle markedly reduced these receptor potentials while causing little change in the resting membrane potential. At high sound levels, where cells responded to an increasingly wider range of sound frequencies, stimulation was less effective in reducing receptor potentials. Since the crossed olivocochlear bundle primarily innervates outer hair cells, these results support an outer hair cell contribution to the most sensitive response region of inner hair cells.

Afferent Pathways↗
PubMed1983

Cochlear inner hair cells: effects of transient asphyxia on intracellular potentials.

Intracellular potentials were recorded from inner hair cells in the guinea pig cochlea. Transient asphyxia was induced by interrupting respiration for brief periods. Asphyxia caused a hyperpolarization of the resting membrane potential (resting Em). The hyperpolarization averaged 2.9 mV for 30 s asphyxias and 5.7 mV for 45 s asphyxias. The membrane potential recovered quickly after normal ventilation was resumed. Asphyxia also induced a rapid and profound decrease of the d.c. receptor potential in response to moderate intensity tone bursts at the characteristic frequency of the inner hair cell. At maximal depression, the receptor potential was reduced about 60% for a 30 s asphyxia and 100% for a 45 s asphyxia. The receptor potential recovered slowly after normal ventilation was resumed. A similar percent reduction and time course of recovery were observed for the a.c. receptor potential. In recordings from the same animals, the round window compound action potential (CAP) was as severely depressed by asphyxia as the hair cell receptor potentials. The time course of recovery for the CAP was similar to the slow recovery of the d.c. receptor potential. In contrast, the round window cochlear microphonics (CM) and the endolymphatic potential (EP) were affected less by asphyxia and recovered quickly after ventilation was resumed. Frequency tuning curves (FTCs) for the d.c. receptor potential were measured during the period of maximal receptor potential depression. These FTCs showed decreased tip sensitivity and a decrease in sharpness of tuning, as measured by the Q10. These changes were fully reversible. Low frequency (tail) segments of the FTCs were much less affected by asphyxia. The inner hair cell FTC changes during asphyxia were compared with neural FTC changes reported by other investigators. The similarities lead us to the conclusion that the inner hair cell and the auditory neural response to sound are equally sensitive to asphyxia.

Animals↗
PubMed1983

Anesthesia and surgical trauma: their influence on the guinea pig compound action potential.

A chronic implant consisting of a fine thermocouple placed on the round window permitted measurement of temperature and of the compound action potential (CAP) of the cochlear nerve in guinea pigs. Thresholds and latencies of the CAP, in response to tone bursts (2-40 kHz), were measured when the animal was awake and unrestrained, and again after several hours of anesthesia. The CAP remained unchanged with a variety of common anesthetics when precise control of round window temperature was maintained. However, when anesthesia was accompanied by several hours of slight cochlear cooling, thresholds were elevated for CAPs evoked by frequencies above 24 kHz and latencies were increased for CAPs evoked by all frequencies tested. The effects of surgery on CAP threshold and latency were also examined. Guinea pigs were tested while still anesthetized at the conclusion of the implantation procedure, and then again several days later while awake. Thresholds and latencies were unchanged. In two anesthetized guinea pigs already implanted with thermocouples, ventral and post-auricular surgery to expose the middle ear had no effect on the CAP, when low-speed drilling was used to open the auditory bulla. However, when small portions of the bulla were broken away with forceps, the CAP in response to high-frequency tone bursts immediately showed elevated thresholds. This alteration of the CAP was clearly different from that produced by lowered temperature, since the latencies at threshold were significantly decreased.

Action Potentials↗
PubMed1983

The temperature dependency of neural and hair cell responses evoked by high frequencies.

A fine thermocouple, placed on the round window of the guinea pig cochlea, was used to measure temperature and electrical potentials. In acute experiments, rectal temperature was held constant at 38 degrees C while cochlear temperature was varied between 38 degrees C and 31.5 degrees C. Cochlear cooling to 36 degrees C caused elevated thresholds for the compound action potential (CAP) in response to tone bursts with frequencies above 24 kHz. CAP latencies increased for all frequencies tested (2 to 40 kHz). Cooling to lower temperatures produced larger latency increases and greater threshold shifts which extended to CAPs evoked by frequencies as low as 16 kHz. These CAP changes were fully reversible after a cochlear temperature of 38 degrees C was restored. In an attempt to create more uniform cooling of the cochlea, experiments were also conducted with round window thermo-couples chronically implanted in guinea pigs. After cooling the entire anesthetized animal to 36 degrees C, CAP thresholds were again elevated only for frequencies above 24 kHz. In other acute experiments, extracellular dc receptor potentials were recorded from the organ of Corti with micropipettes. Cooling caused a decreased sensitivity to tones at the characteristic frequency of the recording location (20 kHz) and had less effect on responses to lower frequencies. The receptor potential usually recovered after rewarming the cochlea. These data emphasize that temperature is an important parameter when electrophysiological measurements are being made. They also suggest an explanation for the reported discrepancy between behavioral and electrophysiological thresholds at high frequencies.

Action Potentials↗
PubMed1982

Acute perilymphatic perfusion of the guinea pig cochlea.

A method for the continuous perfusion of the perilymphatic space of the inner ear in the guinea pig is described. Artificial perilymph is supplied to the cochlea and drained away through a tubing system while flow rates from 10 microliters/min to 0.3 ml/min are established by gravity syphon pressure. Techniques are also presented which allow control over the temperature of the perfusate and over the level of dissolved oxygen in the perfusate. Alone with these variables, the pH of the artificial perilymph can be manipulated and various drugs can be added to the perfusate to test their effect on the inner ear. The function of the inner ear is monitored by continuous recording of the sound evoked bioelectric potentials, the cochlear microphonic and the compound action potential. The cochlear perfusion technique has many applications in the study of cochlear physiology and metabolism, and in testing the sensitivity of the inner ear to ototoxic drugs.

Animals↗
PubMed1981

Inner hair cell responses to the velocity of basilar membrane motion in the guinea pig.

Triangular wave acoustic stimulation at 200 Hz produced the expected square wave cochlear microphonic at the round window membrane and within the scala media. Intracellular recordings from inner hair cells (IHC) of the first cochlear turn showed a combination waveform having both spike impulse and square wave features. The IHC response suggests a sensitivity of these cells to both the displacement and to the velocity of basilar membrane motion.

Acoustic Stimulation↗