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Biomedical subjects

J B Kelly

Publications and source records attributed to J B Kelly.

At least 55 records · Page 3Linked to original sources
PubMed1992

NMDA, non-NMDA and glycine receptors mediate binaural interaction in the lateral superior olive: physiological evidence from mouse brain slice.

Binaural interaction was investigated in a 400 microns brain slice taken through the mouse lateral superior olive (LSO). Ipsilateral excitatory and contralateral inhibitory inputs to LSO neurons were examined by recording physiological responses to electrical stimulation of the trapezoid body. Bath application of non-N-methyl-D-aspartate (non-NMDA) antagonists blocked ipsilateral excitation and strychnine blocked contralateral inhibition. N-methyl-D-aspartate (NMDA) had little effect on ipsilateral responses but completely blocked contralateral inhibition. These results suggest that ipsilateral excitation is mediated by non-NMDA receptors and contralateral inhibition by strychnine dependent glycine receptors. NMDA receptors may play a role by modulating contralateral inhibition in LSO.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1992

Binaural responses in rat inferior colliculus following kainic acid lesions of the superior olive: interaural intensity difference functions.

The binaural responses of cells in the rat's inferior colliculus were determined following either unilateral or bilateral lesions of the superior olivary complex (SOC). The lesions were made by local injection of kainic acid through a glass micropipette lowered stereotaxically into the auditory brain stem. After a recovery period of at least two weeks, neural responses to pure tone pulses were recorded from the inferior colliculus with tungsten microelectrodes inserted into the central nucleus. Attention was focused on neurons that exhibited binaural suppression, ie., were excited by contralateral and inhibited by bilateral stimulation. Binaural suppression responses were still present following complete unilateral destruction of the superior olive either ipsilateral or contralateral to the recording site. Binaural responses were also present following bilateral lesions of the SOC. Furthermore, the shape and slope of interaural intensity difference functions were not statistically different for normal animals and animals with either unilateral or bilateral SOC lesions. No differences were found among lesion groups or between recording sites ipsilateral or contralateral to the lesions. These data suggest that the superior olive is not essential for binaural interaction and that supraolivary structures play a significant role in shaping binaural responses in the inferior colliculus.

Acoustic Stimulation↗
PubMed1992

Midline and lateral field sound localization in the ferret (Mustela putorius): contribution of the superior olivary complex.

1. The ability of ferrets to localize sound in space was determined before and after unilateral or bilateral lesions of the superior olivary complex (SOC). Lesions were made by pressure injection of kainic acid into the SOC through a stereotaxically positioned glass micropipette. The lesions destroyed the cell bodies in the superior olive without disrupting fibers of passage in the trapezoid body or other pathways in the auditory brain stem. The integrity of fibers was demonstrated by protargol staining of axonal processes and by the retrograde transport of horseradish peroxidase (HRP) from the inferior colliculus to other auditory brain stem nuclei. Behavioral tests were carried out separately for sound localization at midline and lateral field positions. Minimum audible angles were determined for single 45-ms noise bursts presented through paired loudspeakers positioned symmetrically around 0, -60, and +60 degrees azimuth. 2. Four ferrets received complete lesions of the left SOC, and two received complete lesions of the right SOC. In general, unilateral destruction of the superior olive resulted in impairments in sound localization in both left and right lateral fields. In some cases, deficits were also apparent on midline. Four additional animals received unilateral lesions that spared cells within the SOC. In most cases, deficits were apparent despite incomplete lesions of the SOC. The pattern of deficits was generally consistent with that found in animals with complete lesions. Most animals had difficulty localizing sounds in the lateral fields. 3. Four animals received bilateral lesions of the SOC. Three had complete or near-complete destruction of the superior olive on one side of the brain with relatively minor damage on the other side. Each of these animals exhibited behavioral deficits that were particularly severe ipsilateral to the more extensively damaged superior olive. One animal with complete bilateral destruction of the SOC was incapable of sound localization, even with 2-s noise bursts. This animal, however, suffered severe motor impairments after surgery that might have contributed to the apparent inability to localize sound. 4. Two animals with kainic acid lesions that caused little or no damage to the SOC were still capable of high levels of performance in tests of sound localization and had no elevation in minimum audible angles. These cases served as controls for the possible effects of nonspecific brain damage and demonstrated that kainic acid injections per se resulted in no obvious deficits in our test situation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Binaural interaction in the lateral superior olive: time difference sensitivity studied in mouse brain slice.

1. The sensitivity of lateral superior olive (LSO) neurons to interaural time differences was examined in an in vitro brain slice preparation. Brain slices, 400-500 microns, were taken through the superior olivary complex of C57 BL/6J mice and were maintained in an oxygenated saline solution for single-unit recording. Both extracellular and intracellular recordings were made with glass pipettes filled with 4 M potassium acetate. Responses were elicited by applying current pulses to the trapezoid body through bipolar stimulating electrodes located ipsilateral or contralateral to the olivary complex. Binaural interactions were studied by manipulating the timing and intensity of paired ipsilateral and contralateral pulses. 2. In extracellular recordings, stimulation of the ipsilateral trapezoid body usually elicited a single action potential, whereas stimulation of the contralateral trapezoid body failed to produce a spike response. Bilateral stimulation resulted in the complete suppression of the evoked spike, indicating the presence of a contralateral inhibitory effect. The degree of inhibition depended on the interpulse interval between ipsilateral and contralateral stimulation. With sufficiently large ipsilateral lead times, the probability of eliciting an extracellular spike was 1.0. As the interpulse interval was gradually shifted to reduce the ipsilateral lead time, the response probability precipitously dropped to 0.0. Most neurons could be completely suppressed by simultaneous stimulation. The dynamic range, defined as the range of interpulse intervals over which response probability changed from 0.9 to 0.1, was between 125 and 225 microseconds for most cells tested. 3. With increasing contralateral lead times, the extracellularly recorded spike was eventually released from inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Inhibitory influence of the dorsal nucleus of the lateral lemniscus on binaural responses in the rat's inferior colliculus.

The contribution of the dorsal nucleus of the lateral lemniscus (DNLL) to binaural processing was examined by recording single-unit activity in the rat's inferior colliculus before, during, and after a reversible block of the excitatory activity in DNLL by local injection of kynurenic acid. Recordings were made from the central nucleus of the inferior colliculus with glass micropipettes filled with 3 M sodium acetate. Kynurenic acid (2 mM in Locke's solution) was injected into the DNLL through one side of a double-barreled glass pipette. The other side of the pipette was filled with Locke's solution for making control injections and recording neural activity. Pressure injection of 0.7-2.0 microliter of kynurenic acid resulted in the complete cessation of tone-evoked responses in DNLL for periods of 45 min to 1 hr. Tone bursts were delivered separately to the two ears through headphones fitted to the external auditory meatus. Binaural responses in the inferior colliculus were determined by comparing the effects of monaural and binaural stimulation. Attention was focused on neurons that were excited by contralateral stimulation and inhibited by ipsilateral stimulation. Interaural intensity difference (IID) functions were generated by holding contralateral sound pressure constant at 10 dB above threshold while increasing ipsilateral sound pressure level. Prior to kynurenic acid injection, ipsilateral stimulation caused a pronounced suppression of contralaterally evoked single-unit activity. Unilateral injection of kynurenic acid into DNLL reduced the strength of binaural suppression in the contralateral inferior colliculus. In every cell tested, the IID curve in inferior colliculus was shifted following contralateral DNLL injection. The IID curve returned to normal after recovery of neural activity in DNLL. In contrast, no effect was seen in the inferior colliculus ipsilateral to the kynurenic acid injection. The injection of Locke's solution into DNLL had no effect on IID curves in the inferior colliculus. These data suggest that the DNLL plays a role in binaural processing through an inhibitory influence on responses in the contralateral inferior colliculus.

Acoustic Stimulation↗
PubMed1992

Synaptic pharmacology of the superior olivary complex studied in mouse brain slice.

The synaptic pharmacology of the lateral superior olive (LSO) and medial nucleus of the trapezoid body (MNTB) was examined in a brain slice preparation of the mouse superior olivary complex (SOC). Physiological responses in SOC were elicited by electrical stimulation of the trapezoid body ipsilateral or contralateral to the recording site, and bilateral interactions were investigated by combined ipsilateral and contralateral stimulation. Pharmacological effects were tested by bath application of amino acid agonists and antagonists. Neurons in MNTB were excited by contralateral stimulation and unaffected by ipsilateral stimulation. Excitatory amino acid (EAA) agonists--kainic acid (KA), quisqualic acid (QA), or L-glutamate--caused spontaneous firing at low concentrations and eliminated responses at higher concentrations in MNTB. The EAA agonist NMDA had relatively little effect at comparable concentrations. Stimulus-elicited responses were blocked by non-NMDA antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 6,7-dinitro-quinoxaline-2,3-dione (DNQX) and by the nonspecific EAA antagonist kynurenic acid, but were unaffected by the NMDA antagonist D,L-2-amino-5-phosphonovaleric acid (APV). LSO neurons were typically excited by ipsilateral stimulation and inhibited by contralateral stimulation. In LSO, KA, QA, and L-glutamate caused spontaneous firing at low concentrations and eliminated responses at higher concentrations, and NMDA had relatively little effect. Excitatory responses in the vast majority of LSO neurons were blocked by CNQX, DNQX, or kynurenic acid. Some responses were also blocked by APV. LSO neurons were affected by glycine, and contralateral inhibition in LSO was completely blocked by strychnine. NMDA also blocked inhibition in LSO. These results indicate that excitation of both MNTB and LSO neurons is mediated primarily by an EAA neurotransmitter through non-NMDA receptors and that contralateral inhibition of LSO cells is mediated through strychnine-dependent glycine receptors. NMDA receptors may play a role in binaural processing by modulating contralateral inhibitory input to LSO.

Amino Acids↗
PubMed1992

Kainic acid lesions of the dorsal nucleus of the lateral lemniscus: effects on binaural evoked responses in rat auditory cortex.

The effects of unilateral lesions of the dorsal nucleus of the lateral lemniscus (DNLL) on binaural processing were examined by measuring the amplitude of auditory cortical evoked responses in the albino rat. Lesions were made by pressure injection of small quantities of kainic acid through a micropipette lowered into the lateral lemniscus. Comparisons were made between normal animals and animals with unilateral DNLL damage. In normal animals, the amplitude of evoked potentials recorded from left and right primary auditory cortex varied as a function of the time difference between clicks delivered to the two ears. Maximum responses were obtained from the hemisphere contralateral to the leading click, and response amplitude was progressively reduced as the interaural time difference (ITD) was shifted in favor of the ipsilateral ear over the range from +600 microseconds to -600 microseconds. The functions in the left and right hemisphere were symmetrical mirror images of one another. Destruction of the DNLL had no significant effect on the maximum response amplitude, evoked response threshold, or response latency in either hemisphere. On the other hand, the lesion did have the effect of greatly reducing the slope of the ITD function in the hemisphere contralateral to the lesion. The change in slope was attributed to a reduction in the strength of inhibition produced by stimulation of the ipsilateral ear. No effect was seen on the slope of the function in the ipsilateral hemisphere. Animals with lesions that spared DNLL but destroyed the intermediate and ventral nucleus of the lateral lemniscus had normal binaural response functions. These data show that the DNLL plays an important role in shaping binaural responses in the contralateral auditory pathway.

Animals↗
PubMed1991

Kainic acid lesions of the superior olivary complex: a horseradish peroxidase study of surviving brain-stem projections.

Lesions of the superior olivary complex of the adult ferret were made by pressure injection of kainic acid (5 nM/microliters in Locke's solution) through a glass micropipette inserted into the lower brain-stem. Small injections of kainic acid (1.5 microliters) produced a localized loss of nerve cells in the superior olivary complex in the vicinity of the pipette tip without apparent damage to fibers of passage in the trapezoid body. The extent of neural damage was determined by the absence of cell bodies in Nissl-stained sections. Integrity of fibers in the trapezoid body and other decussating pathways of the auditory lower brain-stem was confirmed by retrograde transport of horseradish peroxidase (HRP) following large injections of the enzyme into the central nucleus of the inferior colliculus. Even animals with complete destruction of the superior olivary complex had a normal complement of HRP-labelled cells in all divisions of the cochlear nucleus (the dorsal, anteroventral and posteroventral nuclei) contralateral to the HRP injection. In cases with partial lesions, normal labelling was also seen in those parts of the superior olivary complex not directly destroyed by the kainic acid injection. There was no evidence of disruption of fibers of passage nor was there any indication of abnormal projections from the lower brain-stem to inferior colliculus even after prolonged survival times.

Animals↗
PubMed1991

Coding of interaural time differences of transients in auditory cortex of Rattus norvegicus: implications for the evolution of mammalian sound localization.

We obtained quantitative evidence on the coding of interaural time differences (ITDs) of click stimuli by 40 single neurons in the auditory cortex of anesthetized albino rats. Most of the neurons (31/40) received an excitatory input from the contralateral ear, and an inhibitory input from the ipsilateral ear (EI cells). These neurons expressed their sensitivity to ITDs in a sigmoidal relation between spike count and ITD, with maximal responses associated with contralateral-leading ITDs. The mean ITD dynamic range was 590 microseconds. The dynamic ranges typically encompassed at least part of the behaviorally-relevant range (about +/- 130 microseconds). Variations in ITD from 130 microseconds favoring one ear to 130 microseconds favoring the other ear caused spike response rate changes, on average, of 29.5%. These data are similar to those previously presented for the central auditory systems of larger mammals, whose auditory localization acuity is significantly better than that of the rat. We argue, therefore, that the sound localization mechanisms based on transient ITDs have not evolved in a fashion that covaries with interaural distance, and that there exists a mismatch between the ITDs the rat will encounter in the free field, and the ITDs which are encoded by its nervous system. This may be one reason why sound localization acuity has a roughly inverse relation to interaural distance.

Acoustic Stimulation↗
PubMed1991

Sound frequency and binaural response properties of single neurons in rat inferior colliculus.

Sound frequency and binaural response properties were determined for single neurons in the rat's inferior colliculus. Nerve cell responses in the central nucleus of the inferior colliculus were narrowly tuned and had clearly defined characteristic frequencies (CF). The central nucleus was tonotopically organized with low frequencies represented dorsolaterally and high frequencies ventromedially from 0.87 to 45 kHz. Sharpness of tuning, as indicated by Q10, covered a wide range of values for neurons with the same CF, but the maximum Q10 at each frequency increased monotonically with CF. Maximum Q10s were larger than previously reported for auditory cortex at the same CF. Binaural responses were classified as either suppression, summation or mixed. Most of the units encountered exhibited binaural suppression but there were substantial numbers of both summation and mixed responses. Each major binaural response type was distributed broadly across sound frequencies within the rat's hearing range. Binaural suppression responses were most numerous at high frequencies and summation responses at low frequencies. The binaural response types, their relative proportions and their distribution by CF were similar for neurons in the central nucleus of inferior colliculus and primary auditory cortex of the albino rat.

Acoustic Stimulation↗
PubMed1991

Physiological properties of neurons in the mouse superior olive: membrane characteristics and postsynaptic responses studied in vitro.

1. The physiological properties of cells in the superior olivary complex (SOC) were studied in 400-microns brain slices taken through the mouse auditory brain stem. Coronal sections were prepared from fresh brain tissue and were placed fully submerged in an oxygenated saline solution. The boundaries of the medial nucleus of the trapezoid body (MNTB), the lateral superior olive (LSO), and the fibers of the trapezoid body were visualized through a dissecting microscope, and micropipettes filled with 4 M potassium acetate were inserted into the LSO or MNTB. 2. Bipolar stimulating electrodes were placed along the trapezoid body usually at the midline decussation and at a location just lateral to the LSO. This arrangement allowed for stimulation of the trapezoid body both contralateral and ipsilateral to the SOC. Synaptic potentials were elicited by delivering brief (0.1 ms) current pulses to the fibers of the trapezoid body. In some cases the integrity of the fibers was confirmed by transport of horseradish peroxidase (HRP) after extracellular microinjections at various locations along the pathway. The HRP reaction product revealed active transport within the trapezoid body and characteristic synaptic and terminal morphology in the MNTB and LSO. The MNTB contained primarily large-diameter fibers terminating in specialized endings (the calyces of Held), whereas the LSO contained mainly small-diameter fibers and punctate terminal boutons. 3. Membrane characteristics of cells in MNTB and LSO were determined by injecting current into the cell and measuring the corresponding voltage change. Neurons in LSO exhibited a roughly linear relation between voltage and intracellularly injected current. Negative current resulted in a graded hyperpolarization of the cell membrane, and positive current resulted in a graded depolarization that led to the production of action potentials. The number of action potentials was directly related to the strength of the current injected. In contrast, the neurons in MNTB had current-voltage relations that were strongly nonlinear around resting potential. The injection of negative current led to graded hyperpolarization, but injection of positive current produced a limited depolarization that resulted in either a single large action potential or an action potential followed by several spikes with greatly reduced amplitude. 4. Excitatory postsynaptic potentials (EPSPs) could be elicited in LSO by ipsilateral stimulation of the trapezoid body and in MNTB by contralateral stimulation. In response to repeated stimulation, some cells in LSO exhibited temporal summation, that is, a series of slightly subthreshold current pulses produced postsynaptic potentials that combined to elicit action potentials.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1991

Pain syndromes in the cancer patient.

Paraneoplastic syndromes affect the nervous system in a very small percentage of patients with cancer. In those patients, portions of the nervous system are damaged or destroyed, usually in association with a small and often occult neoplasm elsewhere in the body. Current evidence suggests that these syndromes occur when the body mounts an immune response to an antigen shared between the tumor and the nervous system. The immune attack is then misdirected against that portion of the nervous system that possesses the "onconeural" antigen.

Humans↗
PubMed1990

Auditory cortex of the long-eared hedgehog (Hemiechinus auritus). I. Boundaries and frequency representation.

The boundaries of the primary auditory cortex of the long-eared hedgehog, Hemiechinus auritus, were determined by single-cell recordings, myeloarchitecture and retrograde horseradish peroxidase labeling in the medial geniculate, using anesthetized animals. The auditory cortex is located on the lateral surface of the temporal cortex, medial to the rhinal fissure. Responses to pure tones revealed an orderly representation of best frequencies in the primary auditory cortex, with low frequencies represented rostrally and high frequencies caudally. A second auditory field caudal to the primary one was indicated.

Animals↗
PubMed1990

Human evoked potentials to shifts in the lateralization of a noise.

A continuous noise was generated by running a sequence of random numbers through a digital-analog converter and connecting the output through an amplifier and filter to an earphone. Two channels were programmed to generate identical noise stimuli with one channel delayed relative to the other. When these stimuli were presented through earphones, the subject lateralized the noise to the side receiving the leading stimulus. Changes in the relative timing of the two stimuli caused the noise to shift its lateralization. Since these shifts occurred without any detectable change in the ongoing monaural noise, any potentials they evoked were specifically related to binaural interaction. The response recorded from the vertex contained a positive-negative-positive complex with peak latencies of 75, 136 and 220 ms. This response was similar to that evoked by the onset of a monaural stimulus although it was slightly smaller and significantly later. Despite several attempts, we were unable to record any definite earlier evoked potentials.

Adolescent↗
PubMed1989

Brainstem auditory evoked response in the ferret (Mustela putorius).

The effect of click intensity, repetition rate and binaural interaction on the brainstem auditory evoked response (BAER) was examined in sixteen pigmented adult male ferrets. Potentials were recorded from platinum needle electrodes inserted over the vertex and left and right mastoids. Square waves, 100 microseconds in duration, were transduced by earphones enclosed in an assembly designed to fit securely over the ferret's external ear. The BAER in the ferret consists of four prominent vertex-positive peaks (P1-P4) and a fifth peak of smaller amplitude and more variable latency. The mean latencies of P1-P4 at 104 dB peak SPL were 0.96, 1.83, 2.75 and 3.62 ms. Reducing intensity over a 70 dB range resulted in a reduction in amplitude and a corresponding increase in latency ranging between 0.57 and 0.67 ms. Also, increasing click repetition rate resulted in a reduction in amplitude and an increase in latency. With intensity fixed at 104 dB peak SPL comparison of latencies at 10 and 50/s showed a mean increase of 20, 50, 60 and 80 microseconds for P1-P4, respectively. The effect of binaural interaction on the BAER was examined using the procedure of Dobie and Berlin (1979); the response evoked by binaural stimulation was subtracted from the summed left and right monaural responses to obtain a binaural interaction component. Binaural interaction in the ferret gave rise to a distinct vertex-negative wave with a latency similar to P4. An increase in click intensity over a 70 dB range resulted in a monotonic increase in amplitude and a decrease in latency of the binaural interaction component.

Acoustic Stimulation↗
PubMed1989

Coding of tone-pulse amplitude by single neurons in auditory cortex of albino rats (Rattus norvegicus).

We examined the neural representation of tone pulse amplitude in the auditory cortex of anesthetized albino rats. Rate-level functions for monaural, contralateral CF tones were obtained from single neurons. Most of these functions were saturating and monotonic in shape. The dynamic ranges of these functions were typically 5 to 35 dB in breadth, although the tail of this distribution extended to beyond 60 dB. The neurons with the widest dynamic ranges were usually those with the lowest CF thresholds. Nonmonotonic neurons were uncommon, and the nonmonotonicity was not as well developed as that seen in the cortex of cats and monkeys. For two individual rats, data are presented for neurons tuned to the same tone frequency in a single cerebral hemisphere. The CF thresholds of these neurons varied over a 50 dB range, and their collective dynamic ranges spanned at least 70 dB. These data provide a minimum estimate of the dynamic range of the cortical code for tone pulse amplitude in the rat. They suggest that there may be no serious mismatch between the neural and behavioral amplitude dynamic ranges.

Acoustic Stimulation↗
PubMed1988

Primary auditory cortex in the ferret (Mustela putorius): neural response properties and topographic organization.

Microelectrode recording studies were made of the crown of the ectosylvian auditory cortex of barbiturate-anesthetized ferrets, using calibrated, sealed acoustic stimulus delivery systems. We confirmed our previous finding using free-field stimuli that this region of the ferret's cerebral cortex contains a tonotopically organized field in which neurons are briskly excited by the onset of tonal stimuli. The vast majority of neurons in this field were narrowly tuned to tone pulse frequency, with Q factors comparable to those described for cortical cells in other species. The distribution of minimum tone thresholds across the frequency representation of this field paralleled the behavioral audiogram in the same species. The majority of neurons received input from both ears, and the natures of the influences exerted by tonal stimuli at the two ears were similar in form to those described for other carnivores. The various binaural cell types had characteristic frequencies that spanned the entire tonal spectrum represented in the cortex. Preliminary mapping studies revealed that there may be a topographic segregation of cells according to their binaural interactions. The basic properties of cells in this region of the ferret's cerebrum are similar to those previously described for the cat's primary auditory cortex. The data on the binaural properties of these cells, and the spatial distribution of those cells, provide the first evidence in a species other than the cat for segregated binaural representation in the auditory cortex.

Acoustic Stimulation↗