Whole cell recordings of intrinsic properties and sound-evoked responses from the inferior colliculus.

Response features of inferior colliculus (IC) neurons to both current injections and tone bursts were studied with in vivo whole cell recordings in awake Mexican free-tailed bats. Of 160 cells recorded, 95% displayed one of three general types of discharge patterns in response to the injection of positive current: 1) sustained discharges; 2) adapting discharges; and 3) onset-bursting discharges. Sustained neurons were the most common type (N=78), followed by onset-bursting (N=57). The least common type was adapting (N=17). In 90 neurons the profiles of synaptic and discharge activity evoked by tones of different frequencies at 50 dB SPL were recorded. Three major tone-evoked response profiles were obtained; 1) neurons dominated by excitation (N=32) in which tones evoked excitatory post-synaptic potentials (EPSPs) or EPSPs with discharges over a range of frequencies with little or no evidence of inhibitory post-synaptic potentials (IPSPs) evoked by frequencies that flanked the excitation; 2) neurons that had an excitatory frequency region in which discharges were evoked that was flanked by frequencies that evoked predominantly IPSPs (N=26); 3) neurons in which all frequencies evoked IPSPs with little or no depolarizations (N=32). The question we asked is whether IC cells that express a particular profile of PSPs and discharges to acoustic stimulation also have the same current-evoked response profile. We show that, with one exception, the intrinsic features of an IC neuron are not correlated with the pattern of its synaptic innervation; the two features are unrelated in the majority of IC cells. The exception is a subtype of inhibitory dominated cell where most frequencies evoked IPSPs to both the onset and to the offset of the tone bursts. In those cells injected current steps always evoked an onset-bursting response.

MDA improvement technique for lung counter measurements of uranium workers.

A practical and simple method was employed to improve the minimum detectable activity (MDA) for lung counting measurements by summing several accumulated spectra. The method was checked for natural uranium, which produces peaks due to photon energies of 63.3, 92.6 and 185.7 keV. By combining nine measurements, an overall improvement of the MDA by a factor of about 3 was achieved. Uranium contamination levels lower than the MDA of a single spectrum could be detected with acceptable accuracy when analyzing the sum spectra. Specific results are given for four workers occupationally exposed to natural uranium.

Malignant mixed Müllerian tumor with heterologous component arising in the fallopian tube--a case report.

Primary malignant mixed Müllerian tumors (MMMTs) of the fallopian tube are rarities in gynecologic oncology with only 26 cases of MMMTs with a heterologous component reported thus far. We report a case of FIGO Stage II primary MMMT of the fallopian tube with a heterologous tumor portion in an 80-year-old woman presenting with abdominal discomfort at the time of primary diagnosis. After performance of total abdominal hysterectomy, bilateral salpingo-oophorectomy and omentectomy follow-up examination three months postoperatively did not show signs of disease recurrence. The patient finally presented six months after the initial diagnosis with extensive intraabdominal metastasis and died several days thereafter. The present report supports the aggressive nature of these neoplasms. The efficacy of chemotherapy and radiation remains to be defined in future studies.

Reversible inactivation of the dorsal nucleus of the lateral lemniscus reveals its role in the processing of multiple sound sources in the inferior colliculus of bats.

Neurons in the inferior colliculus (IC) that are excited by one ear and inhibited by the other [excitatory-inhibitory (EI) neurons] can code interaural intensity disparities (IIDs), the cues animals use to localize high frequencies. Although EI properties are first formed in a lower nucleus and imposed on some IC cells via an excitatory projection, many other EI neurons are formed de novo in the IC. By reversibly inactivating the dorsal nucleus of the lateral lemniscus (DNLL) in Mexican free-tailed bats with kynurenic acid, we show that the EI properties of many IC cells are formed de novo via an inhibitory projection from the DNLL on the opposite side. We also show that signals excitatory to the IC evoke an inhibition in the opposite DNLL that persists for tens of milliseconds after the signal has ended. During that period, strongly suppressed EI cells in the IC are deprived of inhibition from the DNLL and respond to binaural signals as weakly inhibited or monaural cells. By relieving inhibition at the IC, we show that an initial binaural signal essentially reconfigures the circuit and thereby allows IC cells to respond to trailing binaural signals that were inhibitory when presented alone. Thus, DNLL innervation creates a property in the IC that is not possessed by lower neurons or by collicular EI neurons that are not innervated by the DNLL. That property is a change in responsiveness to binaural signals, a change dependent on the reception of an earlier sound. These features suggest that the circuitry linking the DNLL with the opposite central nucleus of the IC is important for the processing of IIDs that change over time, such as the IIDs generated by moving stimuli or by multiple sound sources that emanate from different regions of space.

Serotonin effects on frequency tuning of inferior colliculus neurons.

We investigated the modulatory effects of serotonin on the tuning of 114 neurons in the central nucleus of the inferior colliculus (ICc) of Mexican free-tailed bats and how serotonin-induced changes in tuning influenced responses to complex signals. We obtained a "response area" for each neuron, defined as the frequency range that evoked discharges and the spike counts evoked by those frequencies at a constant intensity. We then iontophoretically applied serotonin and compared response areas obtained before and during the application of serotonin. In 58 cells, we also assessed how serotonin-induced changes in response areas correlated with changes in the responses to brief frequency-modulated (FM) sweeps whose structure simulated natural echolocation calls. Serotonin profoundly changed tone-evoked spike counts in 60% of the neurons (68/114). In most neurons, serotonin exerted a gain control, facilitating or depressing the responses to all frequencies in their response areas. In many cells, serotonergic effects on tones were reflected in the responses to FM signals. The most interesting effects were in those cells in which serotonin selectively changed the responsiveness to only some frequencies in the neuron's response area and had little or no effect on other frequencies. This caused predictable changes in responses to the more complex FM sweeps whose spectral components passed through the neurons' response areas. Our results suggest that serotonin, whose release varies with behavioral state, functionally reconfigures the circuitry of the IC and may modulate the perception of acoustic signals under different behavioral states.

Accommodative and vergence findings in ocular myasthenia: a case analysis.

Myasthenia gravis (MG) is a neuromuscular disorder that affects skeletal muscles, in particular, the extraocular muscles. Response variability is a hallmark sign. Detailed findings are described in a patient with MG in which the presenting sign was accommodative insufficiency. Objective accommodative findings were recorded 3 years before the onset of myasthenia, soon after the initial diagnosis was made, and then after the treatment commenced with pyridostigmine. In addition, clinical measurements were obtained periodically at different times of the day for various binocular motor functions, including near point of convergence, phoria, fusional and accommodative amplitudes, and relative accommodation. The disease adversely affected all accommodative and vergence findings, with fatigue being the primary disturbance. The therapeutic administration of pyridostigmine improved static measurements of accommodation and vergence and reduced asthenopia. The objective dynamic measurements of accommodation, vergence, and versions were less affected. These findings provide a clear demonstration that both intrinsic and extrinsic ocular muscles may be affected in the prepresbyopic myasthenic patient.

Features of contralaterally evoked inhibition in the inferior colliculus.

Cells in the central nucleus of the inferior colliculus (ICc) receive a large number of convergent inputs that are not only excitatory but inhibitory as well. While the excitatory responses of ICc cells have been studied extensively, less attention has been paid to the effects that inhibitory inputs have on auditory processing in the ICc. The purpose of this study was to examine the role of contralaterally evoked inhibition in single ICc cells in awake Mexican free-tailed bats. To study the contralaterally evoked inhibition, we created background activity by the iontophoretic application of the excitatory neurotransmitters glutamate and aspartate and visualized the inhibition as a gap in the carpet of background activity. We found that 85% of ICc cells exhibit a contralaterally evoked excitation followed by a period of inhibition. The inhibition acts primarily through GABA(A)20 ms) tones in generating persistent inhibition. While the early inhibition has clear roles in the shaping of excitatory response properties to a stimulus, the later persistent component of the inhibition is more enigmatic. The fact that the persistent inhibition lasts well beyond the duration of excitatory inputs to the ICc cell implies that the persistent inhibition may be important for the temporal segregation of the responses to multiple sound sources.

Serotonin differentially modulates responses to tones and frequency-modulated sweeps in the inferior colliculus.

Although almost all auditory brainstem nuclei receive serotonergic innervation, little is known about its effects on auditory neurons. We address this question by evaluating the effects of serotonin on sound-evoked activity of neurons in the inferior colliculus (IC) of Mexican free-tailed bats. Two types of auditory stimuli were used: tone bursts at the neuron's best frequency and frequency-modulated (FM) sweeps with a variety of spectral and temporal structures. There were two main findings. First, serotonin changed tone-evoked responses in 66% of the IC neurons sampled. Second, the influence of serotonin often depended on the type of signal presented. Although serotonin depressed tone-evoked responses in most neurons, its effects on responses to FM sweeps were evenly mixed between depression and facilitation. Thus in most cells serotonin had a different effect on tone-evoked responses than it did on FM-evoked responses. In some neurons serotonin depressed responses evoked by tone bursts but left the responses to FM sweeps unchanged, whereas in others serotonin had little or no effect on responses to tone bursts but substantially facilitated responses to FM sweeps. In addition, serotonin could differentially affect responses to various FM sweeps that differed in temporal or spectral structure. Previous studies have revealed that the efficacy of the serotonergic innervation is partially modulated by sensory stimuli and by behavioral states. Thus our results suggest that the population activity evoked by a particular sound is not simply a consequence of the hard wiring that connects the IC to lower and higher regions but rather is highly dynamic because of the functional reconfigurations induced by serotonin and almost certainly other neuromodulators as well.

Multiple components of ipsilaterally evoked inhibition in the inferior colliculus.

The central nucleus of the inferior colliculus (ICc) receives a large number of convergent inputs that are both excitatory and inhibitory. Although excitatory inputs typically are evoked by stimulation of the contralateral ear, inhibitory inputs can be recruited by either ear. Here we evaluate ipsilaterally evoked inhibition in single ICc cells in awake Mexican free-tailed bats. The principal question we addressed concerns the degree to which ipsilateral inhibition at the ICc suppresses contralaterally evoked discharges and thus creates the excitatory-inhibitory (EI) properties of ICc neurons. To study ipsilaterally evoked inhibition, we iontophoretically applied excitatory neurotransmitters and visualized the ipsilateral inhibition as a gap in the carpet of background activity evoked by the transmitters. Ipsilateral inhibition was seen in 86% of ICc cells. The inhibition in most cells had both glycinergic and GABAergic components that could be blocked by the iontophoretic application of bicuculline and strychnine. In 80% of the cells that were inhibited, the ipsilateral inhibition and contralateral excitation were temporally coincident. In many of these cells, the ipsilateral inhibition suppressed contralateral discharges and thus generated the cell's EI property in the ICc. In other cells, the ipsilateral inhibition was coincident with the initial portion of the excitation, but the inhibition was only 2-4 ms in duration and suppressed only the first few contralaterally evoked discharges. The suppression was so slight that it often could not be detected as a decrease in the spike count generated by increasing ipsilateral intensities. Twenty percent of the cells that expressed inhibition, however, had inhibitory latencies that were longer than the excitatory latencies. In these neurons, the inhibition arrived too late to suppress most or any of the discharges. Finally, in the majority of cells, the ipsilateral inhibition persisted for tens of milliseconds beyond the duration of the signal that evoked it. Thus ipsilateral inhibition has multiple components and one or more of these components are typically evoked in ICc neurons by sound received at the ipsilateral ear.

Analysis of the role of inhibition in shaping responses to sinusoidally amplitude-modulated signals in the inferior colliculus.

Neurons in the central nucleus of the inferior colliculus (ICc) typically respond with phase-locked discharges to low rates of sinusoidal amplitude-modulated (SAM) signals and fail to phase-lock to higher SAM rates. Previous studies have shown that comparable phase-locking to SAM occurs in the dorsal nucleus of the lateral lemniscus (DNLL) and medial superior olive (MSO) of the mustache bat. The studies of MSO and DNLL also showed that the restricted phase-locking to low SAM rates is created by the coincidence of phase-locked excitatory and inhibitory inputs that have slightly different latencies. Here we tested the hypothesis that responses to SAM in the mustache bat IC are shaped by the same mechanism that shapes responses to SAM in the two lower nuclei. We recorded responses from ICc neurons evoked by SAM signals before and during the iontophoretic application of several pharmacological agents: bicuculline, a competitive antagonist for gamma-aminobutyric acid-A (GABAA) receptors; strychnine, a competitive antagonist for glycine receptors; the GABAB receptor blocker, phaclofen, and the N-methyl-D-aspartate (NMDA) receptor blocker, (-)-2-amino-5-phosphonopentanoic acid (AP5). The hypothesis that inhibition shapes responses to SAM signals in the ICc was not confirmed. In >90% of the ICc neurons tested, the range of SAM rates to which they phase-locked was unchanged after blocking inhibition with bicuculline, strychnine or phaclofen, applied either individually or in combination. We also considered the possibility that faster alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors follow high temporal rates of incoming excitation but that the slower NMDA receptors could follow only lower rates. Thus at higher SAM rates, NMDA receptors might generate a sustained excitation that "smears" the phase-locked excitation generated by the AMPA receptors. The NMDA hypothesis, like the inhibition hypothesis, was also not confirmed. In none of the cells that we tested did the application of AP5 by itself, or in combination with bicuculline, cause an increase in the range of SAM rates that evoked phase-locking. These results illustrate that the same response property, phase-locking restricted to low SAM rates, is formed in more than one way in the auditory brain stem. In the MSO and DNLL, the mechanism is coincidence of phase-locked excitation and inhibition, whereas in ICc the same response feature is formed by a different but unknown mechanism.

Features of ipsilaterally evoked inhibition in the dorsal nucleus of the lateral lemniscus.

The dorsal nucleus of the lateral lemniscus (DNLL) is a binaural nucleus whose neurons are excited by stimulation of the contralateral ear and inhibited by stimulation of the ipsilateral ear. Here we report on several features of the ipsilaterally evoked inhibition in 95 DNLL neurons of the mustache bat. These features include its dependence on intensity, its tuning and the types of stimuli that are capable of evoking it. Inhibition was studied by evoking discharges with the iontophoretic application of glutamate, and then evaluating the strength and duration of the inhibition of the glutamate evoked background activity produced by stimulation of the ipsilateral ear. Excitatory responses were evoked by stimulation of the contralateral ear with best frequency (BF) tone bursts. Glutamate evoked discharges could be inhibited in all DNLL neurons and the inhibition often persisted for periods ranging from 10 to 50 ms beyond the duration of the tone burst that evoked it. The duration of the persistent inhibition increased with stimulus intensity. Stimulus duration had little influence on the duration of the persistent inhibition. Signals as short as 2 ms suppressed discharges for as long as 30 ms after the signal had ended. The frequency tuning of the total period of inhibition and the period of persistent inhibition were both closely matched to the tuning evoked by stimulation of the contralateral ear. Moreover, the effectiveness of complex signals for evoking persistent inhibition, such as brief FM sweeps and sinusoidally amplitude and frequency modulated signals, was comparable to that of tone bursts at the neuron's excitatory BF, so long as the complex signal contained frequencies at or around the neuron's excitatory BF. We also challenged DNLL cells with binaural paradigms. In one experiment, we presented a relatively long (40 ms) BF tone burst of fixed intensity to the contralateral ear, which evoked a sustained discharge, and a shorter, 10 ms signal of variable intensity to the ipsilateral ear. As the intensity of the 10 ms ipsilateral signal increased, it generated progressively longer periods of persistent inhibition and thus the discharges were suppressed for periods far longer than the 10 ms duration of the ipsilateral signal. With interaural time disparities, ipsilateral signals that led contralateral signals evoked a persistent inhibition that suppressed the responses to the trailing contralateral signals for periods of a least 15 ms. This suggests that an initial binaural sound that favors the ipsilateral ear should suppress the responses to trailing sounds that normally would be excitatory if they were presented alone. We hypothesize a circuit that generates the persistent inhibition and discuss how the results with binaural signals support that hypothesis.

Processing of interaural intensity differences in the LSO: role of interaural threshold differences.

Cells in the lateral superior olive (LSO) are known to be sensitive to interaural intensity differences (IIDs) in that they are excited by IIDs that favor the ipsilateral ear and inhibited by IIDs that favor the contralateral ear. For each LSO neuron there is a particular IID that causes a complete inhibition of discharges, and the IID of complete inhibition varies from neuron to neuron. This variability in IID sensitivity among LSO neurons is a key factor that allows for the coding of a variety of IIDs among the population of cells. A fundamental question concerning the coding of IIDs is: how does each cell in the LSO derive its particular IID sensitivity? Although there have been a large number of neurophysiological studies on the LSO, this question has received little attention. Indeed, the only reports that have directly addressed this question are those of Reed and Blum, who modeled the binaural properties of LSO neurons and proposed that the IID at which discharges are completely suppressed should correspond to the difference in threshold between the excitatory, ipsilateral and inhibitory, contralateral inputs that innervate each LSO cell. The main purpose of this study was to test the threshold difference hypothesis proposed by Reed and Blum by recording responses to monaural stimulation and to IIDs from single cells in the LSO of the mustache bat. Our results show that although the IID sensitivities of some LSO cells correspond to the difference in threshold between the excitatory and inhibitory ears, in the majority of cells the difference in thresholds did not correspond to the cell's IID sensitivity. The results lead us to propose two models to account for IID sensitivities. One model is similar to that proposed by Reed and Blum and emphasizes differences in the thresholds of the excitatory and inhibitory inputs. This model accounts for the minority of cells in which the IID of complete inhibition corresponded to the difference in threshold of the inputs from the two ears. The other model, which accounts for the cells in which the IID of complete inhibition did not correspond to the difference in the thresholds of the inputs from the two ears (the majority of cells), places emphasis on differences in latencies of the excitatory and inhibitory inputs. The models incorporate features that are concordant with the known properties of the neurons that project to the LSO and together can account for the diversity of IID sensitivities among the population of LSO neurons.

Roles of GABAergic inhibition for the binaural processing of multiple sound sources in the inferior colliculus.

This review explores the questions of how spike trains that originate from lower auditory nuclei interact in the inferior colliculus to produce an output that synthesizes the information from all these sources. The focus is on the processing of interaural intensity disparities, the cues animals use to localize high-frequency sounds, and the roles of the lateral superior olives and the dorsal nucleus of the lateral lemniscus (DNLL) in shaping the binaural properties of their targets in the inferior colliculus. The main points advanced in this review are 1) that the DNLL shapes the binaural properties of many inferior collicular neurons, 2) that the inhibitory inputs to the DNLL allow it to act as a switch that can be turned on or off with appropriate acoustic stimulation, and 3) that when two or more stimuli are presented, each from a different region of space, the first stimulus can switch the DNLL to its off position. The consequence of the initial stimulus is that stimuli that follow shortly thereafter cannot activate the DNLL, and thus the binaural properties of those collicular cells that receive inhibition from the DNLL are changed. The implications of this switching action are that the location of the initial signal is coded appropriately, whereas the coding of the location of the signal or signals that follow the initial signal is smeared, and consequently, those following signals cannot be accurately localized. In short, it is proposed that the DNLL plays a pivotal role in the way the locations of multiple sound sources are coded by the auditory system.

Differential response properties to amplitude modulated signals in the dorsal nucleus of the lateral lemniscus of the mustache bat and the roles of GABAergic inhibition.

We studied the phase-locking of 89 neurons in the dorsal nucleus of the lateral lemniscus (DNLL) of the mustache bat to sinusoidally amplitude modulated (SAM) signals and the influence that GABAergic inhibition had on their response properties. Response properties were determined with tone bursts at each neuron's best frequency and then with a series of SAM signals that had modulation frequencies ranging from 50-100 to 800 Hz in 100-Hz steps. DNLL neurons were divided into two principal types: sustained neurons (55%), which responded throughout the duration of the tone burst, and onset neurons (45%), which responded only at the beginning of the tone burst. Sustained and onset neurons responded differently to SAM signals. Sustained neurons responded with phase-locked discharges to modulation frequencies < or = 400-800 Hz. In contrast, 70% of the onset neurons phase-locked only to low modulation frequencies of 100-300 Hz, whereas 30% of the onset neurons did not phase-lock to any modulation frequency. Signal intensity differentially affected the phase-locking of sustained and onset neurons. Sustained neurons exhibited tight phase-locking only at low intensities, 10-30 dB above threshold. Onset neurons, in contrast, maintained strong phase-locking even at relatively high intensities. Blocking GABAergic inhibition with bicuculline had different effects on the phase-locking of sustained and onset neurons. In sustained neurons, there was an overall decline in phase-locking at all modulation frequencies. In contrast, 70% of the onset neurons phase-locked to much higher modulation frequencies than they did when inhibition was intact. The other 30% of onset neurons phase-locked to SAM signals, although they fired only with an onset response to the same signals before inhibition was blocked. In both cases, blocking GABAergic inhibition transformed their responses to SAM signals into patterns that were more like those of sustained neurons. We also propose mechanisms that could explain the differential effects of GABAergic inhibition on onset neurons that locked to low modulation frequencies and on onset neurons that did not lock to any SAM signals before inhibition was blocked. The key features of the proposed mechanisms are the absolute latencies and temporal synchrony of the excitatory and inhibitory inputs.

Neural delays shape selectivity to interaural intensity differences in the lateral superior olive.

Neurons in the lateral superior olive (LSO) respond selectively to interaural intensity differences (IIDs), one of the chief cues used to localize sounds in space. LSO cells are innervated in a characteristic pattern: they receive an excitatory input from the ipsilateral ear and an inhibitory input from the contralateral ear. Consistent with this pattern, LSO cells generally are excited by sounds that are more intense at the ipsilateral ear and inhibited by sounds that are more intense at the contralateral ear. Despite their relatively homogeneous pattern of innervation, IID selectivity varies substantially from cell to cell, such that selectivities are distributed over the range of IIDs that would be encountered in nature. For some time, researchers have speculated that the relative timing of the excitatory and inhibitory inputs to an LSO cell might shape IID selectivity. To test this hypothesis, we recorded from 50 LSO cells in the free-tailed bat while presenting stimuli that varied in interaural intensity and in interaural time of arrival. The results suggest that, for more than half of the cells, the latency of inhibition was several hundred microseconds longer than the latency of excitation. Increasing the intensity to the inhibitory ear shortened the latency of inhibition and brought the timing of the inputs from the two ears into register. Thus, a neural delay of the inhibition helped to define the IID selectivity of these cells, accounting for a significant part of the variation in selectivity among LSO cells.

Afferent connections to the dorsal nucleus of the lateral lemniscus of the mustache bat: evidence for two functional subdivisions.

The dorsal nucleus of the lateral lemniscus (DNLL) of the mustache bat, Pteronotus parnellii, was found to consist of two divisions. The neurons in each division were distinguished by their temporal discharge patterns evoked both by tone bursts and sinusoidal amplitude-modulated (SAM) signals. Neurons in the anterior one-third of the DNLL responded to tone bursts with an onset discharge pattern and only phase-locked to SAM signals with low modulation frequencies (< 300 Hz). Neurons in the posterior two-thirds of the DNLL responded to tone bursts with a sustained discharge pattern and phase-locked to SAM signals with much higher modulation frequencies (400-800 Hz). In addition, there was a different frequency representation in the two divisions. The frequency representation in the posterior division was from about 15 to 120 kHz, whereas in the anterior division it was only up to 62 kHz. The physiological differences were further supported by data from experiments that revealed the sources of afferent projections to the two DNLL divisions. Retrograde labeling showed that the afferent projections to the two divisions were from different neuronal populations. Input differences were of two types. Some nuclei projected to one or the other DNLL division, but not to both. For instance, the ventral nucleus of the lateral lemniscus projected predominately to the anterior DNLL and provided little or no inputs to the posterior DNLL, whereas the medial superior olive innervated the posterior but not the anterior DNLL. Other lower nuclei projected to both DNLL divisions. These include the contralateral cochlear nucleus, the ipsi- and contralateral lateral superior olives, the intermediate nucleus of the lateral lemniscus, and the contralateral DNLL. However, the projections to each division of the DNLL originate from different neuronal subpopulations in each lower nucleus. The functional implications of these findings are discussed in the context of the possible impacts that the two DNLL divisions exert on their postsynaptic targets in the inferior colliculus.

Activation of a murine autoreactive B cell by immunization with human recombinant autoantigen La/SS-B: characterization of the autoepitope.

Immunization of Balb/c mice with a homogeneously purified recombinant human La/SS-B protein resulted in activation of an autoreactive B cell secreting a novel monoclonal anti-La antibody termed La4B6. La4B6 reacted with La protein from a variety of sources including human, bovine, rat and mouse. ATP blocked the binding of La4B6 to recombinant La protein. The human epitope was identified as consisting of the amino acid sequence SKGRRFKGKGKGN, which includes the proposed ATP-binding site of the La protein. In the human and bovine La protein, the epitope exists as a continuous amino acid sequence. In rat and mouse the epitope was found to consist of the amino acid sequence SKG interrupted by a species-specific insert of 16 amino acids, and followed by the second half of the epitope, the amino acid sequence RRFKGKGKGN. Our data suggest that in the case of the rat and mouse La proteins the two separated parts of the epitope are able to form a conformational epitope which looks similar to the continuous human epitope.

Glycine and GABA influence binaural processing in the inferior colliculus of the mustache bat.

1. The mammalian inferior colliculus contains large populations of binaural cells that are excited by stimulation of the contralateral ear and are inhibited by stimulation of the ipsilateral ear, and are called excitatory/inhibitory (EI) cells. Neurons with EI properties are initially created in the lateral superior olive (LSO), which, in turn, sends strong bilateral projections to the inferior colliculus. The questions that we address in this report are 1) whether the inhibition evoked by stimulation of the ipsilateral ear occurs at the inferior colliculus or whether it occurs in a lower nucleus, presumably the LSO; and 2) if the ipsilaterally evoked inhibition occurs at the inferior colliculus, is the inhibition a consequence of glycinergic innervation or is it a consequence of GABAergic innervation. To study these questions, we recorded from 61 EI neurons in the inferior colliculus of the mustache bat before and during the iontophoretic application of the glycine receptor antagonist, strychnine. We also tested the effects of the gamma-aminobutyric acid-A (GABAA) receptor antagonist, bicuculline, on 38 of the 61 neurons that were tested with strychnine. The main finding is that glycinergic or GABAergic inhibition, or both, contribute to the ipsilaterally evoked inhibition in approximately 50% of the EI neurons in the inferior colliculus. 2. Strychnine and bicuculline had different effects on the magnitude of the spike counts evoked by stimulation of the contralateral (excitatory) ear. On average, strychnine caused the maximum spike count evoked by contralateral stimulation to increase by only 23%. The relatively small effects of strychnine on response magnitude are in marked contrast to the effects of bicuculline, which usually caused much larger increases in spike counts. For example, although strychnine caused spike counts to more than double in approximately 25% of the collicular neurons, bicuculline caused a doubling of the spike count in approximately 60% of the cells. 3. The inhibitory influences of ipsilateral stimulation were evaluated by driving the neurons with a fixed intensity at the contralateral ear and then documenting the reductions in spike counts due to the presentation of progressively higher intensities at the ipsilateral ear. In 64% of the neurons sampled, blocking glycinergic inhibition with strychnine had little or no effect on the ipsilaterally evoked inhibition. These cells remained as strongly inhibited during the application of strychnine as they did before its application. In addition, the ipsilateral intensity that produced complete or nearly complete spike suppression in the predrug condition was also unchanged by strychnine. 4. In 36% of the neurons, strychnine markedly reduced the degree of ipsilaterally evoked spike suppression. In five of these neurons, there was a complete elimination of the ipsilateral inhibition: these neurons were transformed from strongly inhibited EI neurons into monaural neurons. 5. The influence of both strychnine and bicuculline was tested sequentially in 38 neurons. In about one-half of these cells, (53%, 20/38) the ipsilaterally evoked inhibition was unaffected by either drug. In 10 other units (26%), both drugs substantially reduced or eliminated the ipsilaterally evoked inhibition. In most of these cells, both bicuculline and strychnine reduced the ipsilaterally evoked inhibition to a similar degree. In the remaining eight cells studied with both drugs (21%), the ipsilaterally evoked inhibition was reduced or eliminated by one of the drugs, but not by both. 6. These results show that both glycinergic and GABAergic projections influence the ipsilaterally evoked inhibition in about one-half of the EI neurons in the inferior colliculus. The glycinergic inhibition elicited by ipsilateral stimulation is most likely due to projections from the ipsilateral lateral superior olive, whereas the GABAergic inhibition evoked by ipsilateral stimulation is most likely caused b

GABA and glycine in the central auditory system of the mustache bat: structural substrates for inhibitory neuronal organization.

The distribution and morphology of neurons and axonal endings (puncta) immunostained with antibodies to gamma-aminobutyric acid (GABA) and glycine (Gly) were analyzed in auditory brainstem, thalamic, and cortical centers in the mustache bat. The goals of the study were (1) to compare and contrast the location of GABAergic and glycinergic neurons and puncta, (2) to determine whether nuclei containing immunoreactive neurons likewise have a similar concentration of puncta, (3) to assess the uniformity of immunostaining within a nucleus and to consider regional differences that were related to or independent of cytoarchitecture, and (4) to compare the patterns recognized in this bat with those in other mammals. There are nine major conclusions. (1) Glycinergic immunostaining is most pronounced in the hindbrain. (2) In the forebrain, GABA alone is present. (3) Some nuclei have GABAergic or glycinergic neurons exclusively; a few have neither. (4) Although there is sometimes a close relationship between the relative number of immunopositive neurons and the density of the puncta, just as often there is no particular correlation between them; this reflects the fact that many GABAergic and glycinergic neurons project beyond their nucleus of origin. (5) Even nuclei devoid of or with few GABAergic or glycinergic neurons contain relatively abundant numbers of puncta; some neurons receive axosomatic terminals of each type. (6) In a few nuclei there are physiological subregions with specific local patterns of immunostaining. (7) The patterns of immunostaining resemble those in other mammals; the principal exceptions are in nuclei that, in the bat, are hypertrophied (such as those of the lateral lemniscus) and in the medial geniculate body. (8) Cellular colocalization of GABA and Gly is specific to only a few nuclei. (9) GABA and glutamic acid decarboxylase (GAD) immunostaining have virtually identical distributions in each nucleus. Several implications follow. First, the arrangements of GABA and Gly in the central auditory system represent all possible patterns, ranging from mutually exclusive to overlapping within a nucleus to convergence of both types of synaptic endings on single neurons. Second, although both transmitters are present in the hindbrain, glycine appears to be dominant, and it is often associated with circuitry in which precise temporal control of aspects of neuronal discharge is critical. Third, the auditory system, especially at or below the level of the midbrain, contains significant numbers of GABAergic or glycinergic projection neurons. The latter feature distinguishes it from the central visual and somatic sensory pathways.