The use of kainic acid for studying the origins of scalp-recorded auditory brainstem responses in the guinea pig

Kainic acid was injected into the medial nucleus of the trapezoid body (MNTB) of guinea pigs to evaluate its use in studying generator loci of the scalp-recorded auditory brain stem response (ABR). Sound-evoked near-field potentials from the MNTB and far-field ABRs were recorded before, during and up to 2 h after the injections. Two hours post-injection, small amounts of kainic acid (0.25 nmol in 0.1 [mu]l of Ringer solution) resulted in neuronal destruction which histologically appeared confined to the MNTB. Larger amounts (10 nmol in 1.0 [mu]l) produced more extensive lesions. Regardless of the dose of kainic acid, near-field activity evoked by contralateral ear stimulation was almost totally abolished and ABR wave III amplitude was reduced by as much as 60%. In future studies, the use of excitotoxic amino acids to produce lesions within complex nuclear subdivisions of the auditory pathway may yield valuable information as to the relative contributions that brainstem structures make to the various waves comprising the ABR and about the behavioral effects that axon sparing lesions produce.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24227/1/0000487.pd

An energy-dependent step in aminoglycoside ototoxicity: Prevention of gentamicin ototoxicity during reduced endolymphatic potential

Guinea pigs received a bolus of gentamicin (10 mM for 5 min) by perilymphatic perfusion which normally led to an irreversible loss of the cochlear microphonic potential (CM). Various experimental conditions that reduced the endolymphatic potential (EP) were then superimposed on the gentamicin application. Reversible reductions in EP (and, concomitantly, in CM) were induced by asphyxia (3 min), intravenous furosemide (50 mg/kg), and perilymphatic perfusion of aminooxyacetic acid (10 mM). When the administration of gentamicin was initiated at the time of maximal EP reduction the usual irreversible gentamicin-induced decline of CM was prevented.The results indicate that a metabolic process is essential in the expression of gentamicin toxicity. The data are consistent with the inhibition of an energy-dependent transport of the aminoglycoside. Alternatively, the data are also compatible with the hypothesis that entry of gentamicin into hair cells is prevented by a reduction in their transmembrane electrical potential.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25874/1/0000437.pd

Analysis of histamine as a hair-cell transmitter in the lateral line of Xenopus laevis

The actions of histamine and histamine antagonists on afferent nerve activity were investigated in the lateral line of Xenopus laevis. Histamine (0.002-2.0 mM) had no effect on spontaneous activity or excitatory responses to water motion. In contrast, pyrilamine, an H1 receptor antagonist, suppressed spontaneous activity beginning at 0.01-0.05 mM. Below 0.3 mM the suppression was often preceded by a small excitatory response and responses to high (24-30 dB re threshold), but not low (0-18 dB) levels of water motion were selectively suppressed. Higher concentrations (0.3-2.0 mM) abolished spontaneous activity and suppressed responses at all levels of water motion. Cimetidine, an H2 receptor antagonist, had similar actions but was one-tenth as potent as pyrilamine. Tetrodotoxin (0.001-0.1 [mu]M), which blocks voltage-sensitive Na+ channels, mimicked the suppressive effects of the histamine antagonists. Histamine (2.0 mM) failed to block the actions of pyrilamine (0.1 mM) indicating its effects are mediated through a mechanism other than histamine receptors. In addition, pyrilamine (0.05-0.1 mM) non-selectively suppressed excitation to exogenously applied -glutamate (1.0-2.0 mM), -aspartate (1.0-2.0 mM), kainate (0.005-0.01 mM), and quisqualate (0.002-0.005 mM) and altered responses to (0.5-1.0 mM). The results are inconsistent with histamine being a transmitter in the Xenopus lateral line and reveal that the actions of histamine antagonists are nonspecific, possibly due, in part, to blockade of voltage-sensitive Na+ channels.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28027/1/0000465.pd

Spatial representation of corticofugal input in the inferior colliculus: a multicontact silicon probe approach

The inferior colliculus (IC) is a well-established target of descending projections from the auditory cortex (AC). However, our understanding of these pathways has been limited by an incomplete picture of their functional influence within the three-dimensional space of the IC. Our goal was to study the properties and spatial representation of corticofugal input in the IC of guinea pigs with a high degree of spatial resolution. We systematically mapped neural activity in the IC using two types of silicon substrate probes that allow for simultaneous recording at multiple neural sites. One probe provided a high resolution in the dorsal-ventral plane and the other provided spatial resolution in the medial-lateral plane. Electrical stimulation of the ipsilateral AC produced excitatory responses in the IC with thresholds usually below 5–10 µA. First spike latencies were predominantly in the 6–20 ms range, although latencies from 3–5 ms were also observed. Broadly distributed unimodal spike patterns with modal latencies greater than 30 ms were occasionally seen. The excitatory responses to cortical stimulation were mostly unimodal and occasionally bimodal with a wide range of spike distribution patterns and response durations. Excitation was often followed by suppression of spontaneous activity. Suppression of acoustic responses was observed even when there was little or no response to electrical stimulation, suggesting spatial-temporal integration. A few of the responding neurons showed purely inhibitory responses to electrical stimulation, suggesting that there are disynaptic routes of corticocollicular inhibition. Detailed spatial mapping revealed that the response patterns and their durations had a characteristic spatial distribution in the IC.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46534/1/221_2003_Article_1671.pd

Potassium-induced release of endogenous glutamate and two as yet unidentified substances from the lateral line of Xenopus laevis

The release of endogenous glutamate and other primary amines from the lateral line of Xenopus laevis was studied using an in vitro superfusion technique and high performance liquid chromatography. Potassium stimulation (50 mM KCl) applied to 60 or 120 lateral-line organs dissected from the skin and pooled in a perfusion chamber induced the release of glutamate and aspartate. The release of aspartate was smaller than that of glutamate and more variable. A variable release of two, as yet, unidentified substances was also detected. In low calcium (0.1 mM CaCl2), high magnesium (10 mM MgCl2) solution, 50 mM potassium failed to induce an increase in glutamate, aspartate and the two unknowns, suggesting they are released in a transmitter-like manner. The technique presents a new and simple method for studying transmitters in hair-cell systems. Although other interpretations are possible, the results are consistent with the hypothesis that glutamate is a hair-cell transmitter and suggest a potential role for other substances in the transduction process, perhaps as neuromodulators.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27844/1/0000254.pd

Design and testing of conductive polysilicon beam leads for use in a high-density biomedical connector

A study was conducted to measure and characterize the reliability of polysilicon cantilever beams with electroplated gold pads for use in a high-density biomedical connector. In this design, an array of beams is brought into contact with a corresponding array of 30 µm high gold bumps, forming electrical connection. Analytical computations of multi-layer beams were performed, including the effects of residual stresses. Beam leads of various lengths and widths with electroplated gold contact pads on their ends were tested over 1000 cycles to determine their mechanical reliability, and to measure their contact resistance with gold bumps on a separate substrate. The dimensions of the polysilicon beam that produce the least breakage were determined to be 400 µm long by 125 µm wide. For a beam having a calculated contact force of ∼100 µN, the initial contact resistance was 764 mΩ. After 1000 connect/disconnect cycles, beams of this type had an average final contact resistance of 1.598 Ω. These results demonstrate that very high-density connectors with high mechanical reliability and low-contact resistance can be fabricated.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49046/2/jmm4_7_017.pd

Comparative actions of gaba and acetylcholine on the Xenopus laevis lateral line

1. The effects of GABA, acetylcholine and carbachol on the spontaneous activity of afferent nerve fibers in the lateral line of Xenopus laevis are characterized.2. Atropine and bicuculline were also tested on drug- and water motion-evoked activity.3. GABA (0.019-1.25 mM) suppressed and both acetylcholine (1.25-80 [mu]M) and carbachol (1.25-40 [mu]M) increased spontaneous activity. These actions were blocked by bicuculline (100 [mu]M) and atropine (4 [mu]M) respectively.4. Atropine (20 [mu]M) and bicuculline (100 [mu]M) had no effect on water motion-evoked activity.5. The results characterize actions of GABA and acetylcholine not previously described and provide evidence that does not support the hypothesis that GABA or acetylcholine are the afferent transmitter.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25886/1/0000449.pd

Disruption of Lateral Olivocochlear Neurons via a Dopaminergic Neurotoxin Depresses Sound-Evoked Auditory Nerve Activity

We applied the dopaminergic (DA) neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the guinea pig cochlear perilymph. Immunolabeling of lateral olivocochlear (LOC) neurons using antibodies against synaptophysin was reduced after the MPTP treatment. In contrast, labeling of the medial olivocochlear innervation remained intact. As after brainstem lesions of the lateral superior olive (LSO), the site of origin of the LOC neurons, the main effect of disrupting LOC innervation of the cochlea via MPTP was a depression of the amplitude of the compound action potential (CAP). CAP amplitude depression was similar to that produced by LSO lesions. Latency of the N1 component of the CAP, and distortion product otoacoustic emission amplitude and adaptation were unchanged by the MPTP treatment. This technique for selectively lesioning descending LOC efferents provides a new opportunity for examining LOC modulation of afferent activity and behavioral measures of perception.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41386/1/10162_2004_Article_2429.pd

Descending projections to the dorsal and ventral divisions of the cochlear nucleus in guinea pig

The origins of extrinsic projections to the guinea pig dorsal and ventral cochlear nuclei were identified by examining the retrograde transport of horseradish peroxidase conjugated to wheatgerm agglutinin following its injection into each of these divisions. Major projections originated in periolivary regions of the superior olivary complex, the contralateral cochlear nucleus and the inferior colliculus. There was no contribution from the nuclei of the lateral lemniscus to these pathways. The heaviest projection from the periolivary regions to both divisions of the cochlear nucleus arose bilaterally in the ventral nucleus of the trapezoid body. The ipsilateral lateral nucleus of the trapezoid body also projected heavily to dorsal and ventral cochlear nucleus. In addition, the ventral cochlear nucleus received a substantial projection from the dorsal aspect of the ipsilateral dorsomedial periolivary nucleus. Projections originating bilaterally in the central nucleus of the inferior colliculus terminated in the deep layers of dorsal cochlear nucleus. These projections appear to be more strongly ipsilateral and specific than those reported in the cat.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29434/1/0000515.pd

Comparative actions of salicylate on the amphibian lateral line and guinea pig cochlea

1. 1. Salicylate actions on afferent nerve activity in the Xenopus lateral line and on cochlear potentials in guinea pig were investigated.2. 2. In the lateral line, salicylate (0.3-2.5 mM) suppressed spontaneous activity, water motion evoked excitation and responses to -glutamate (1-2 mM) and kainate (10-20[mu]M).3. 3. In the guinea pig, salicylate (0.6-10 mM) suppressed the compound action potential (CAP) and increased N1 latency at low but not high sound intensities.4. 4. In the lateral line salicylate action may involve an antagonism of the hair-cell transmitter on the afferent nerve.5. 5. In the cochlea salicylate may suppress the active process or cochlear amplifier.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28123/1/0000573.pd