Lateral Superior Olive Neurons Research Articles

Regulation of Intracellular Chloride by Cotransporters in Developing Lateral Superior Olive Neurons

The regulatory mechanisms of intracellular Cl- concentration ([Cl-]i) were investigated in the lateral superior olive (LSO) neurons of various developmental stages by taking advantage of gramicidin perforated patch recording mode, which enables neuronal [Cl-]i measurement. Responses to glycine changed from depolarization to hyperpolarization during the second week after birth, resulting from [Cl-]i decrease. Furosemide equally altered the [Cl-]i of both immature and mature LSO neurons, indicating substantial contributions of furosemide-sensitive intracellular Cl- regulators; i.e., K+-Cl- cotransporter (KCC) and Na+-K+-Cl- cotransporter (NKCC), throughout this early development. Increase of extracellular K+ concentration and replacement of intracellular K+ with Cs+ resulted in [Cl-]i elevation at postnatal days 13-15 (P13-P15), but not at P0-P2, indicating that the mechanism of neuronal Cl- extrusion is sensitive to both furosemide and K+-gradient and poorly developed in immature LSO neurons. In addition, removal of extracellular Na+ decreased [Cl-]i at P0-P2, suggesting the existence of extracellular Na+-dependent and furosemide-sensitive Cl- accumulation in immature LSO neurons. These data show clearly that developmental changes of Cl- cotransporters alter [Cl-]i and are responsible for the switch from the neonatal Cl- efflux to the mature Cl- influx in LSO neurons. Such maturational changes in Cl- cotransporters might have the important functional roles for glycinergic and GABAergic synaptic transmission and the broader implications for LSO and auditory development.

Projection Neurons in the Superior Olivary Complex of the Rat Auditory Brainstem: A Double Retrograde Tracing Study

The superior olivary complex (SOC), a group of interrelated brainstem nuclei, sends efferents to a variety of neuronal structures including the cochlea and the inferior colliculus (IC). In the present study conducted in rats, we sought to investigate whether single SOC efferent neurons project to both cochlea and IC. These neurons were identified by retrograde axonal transport of the neuronal tracers fluoro-gold upon application to the cochlea and cholera toxin B subunit injected into the central nucleus of the IC. Projections to the cochlea were found to stem predominantly from the ipsilateral lateral superior olive (LSO) and medial superior olive (MSO) as well as from the bilateral superior paraolivary nucleus (SPO), dorsal periolivary groups (DPO) and the medial nucleus of the trapezoid body (MNTB). Neurons innervating the IC were seen in the bilateral LSO and DPO, in the SPO predominantly ipsilateral, as well as in the ipsilateral MSO and MNTB. We further observed that some neurons in the ipsilateral LSO, and a considerable part of those of the SPO were double-labeled. However, cells projecting to either IC or cochlea were much more numerous than double-labeled neurons.

A Developmental Shift from GABAergic to Glycinergic Transmission in the Central Auditory System

GABAergic and glycinergic circuits are found throughout the auditory brainstem, and it is generally assumed that transmitter phenotype is established early in development. The present study documents a profound transition from GABAergic to glycinergic transmission in the gerbil lateral superior olive (LSO) during the first 2 postnatal weeks. Whole-cell voltage-clamp recordings were obtained from LSO neurons in a brain slice preparation, and IPSCs were evoked by electrical stimulation of the medial nucleus of the trapezoid body (MNTB), a known glycinergic projection in adult animals. GABAergic and glycinergic components were identified by blocking transmission with bicuculline and strychnine (SN), respectively. In the medial limb of LSO, there was a dramatic change in the GABAergic IPSC component, decreasing from 78% at postnatal day 3 (P3)-P5 to 12% at P12-P16. There was an equal and opposite increase in the glycinergic component during this same period. Direct application of GABA also elicited significantly larger amplitude and longer duration responses in P3-P5 neurons compared with glycine-evoked responses. In contrast, MNTB-evoked IPSCs in lateral limb neurons were more sensitive to SN throughout development. Consistent with the electrophysiological observations, there was a reduction in staining for the beta2,3-GABAA receptor subunit from P4 to P14, whereas staining for the glycine receptor-associated protein gephyrin increased. Brief exposure to baclofen depressed transmission at excitatory and inhibitory synapses for approximately 15 min, suggesting a GABAB-mediated metabotropic signal. Collectively, these data demonstrate a striking switch from GABAergic to glycinergic transmission during postnatal development. Although GABA and glycine elicit similar postsynaptic ionotropic responses, our results raise the possibility that GABAergic transmission in neonates may play a developmental role distinct from that of glycine.

Single-neuron modeling of LSO unit responses.

We investigated, using a computational model, the biophysical correlates of measured discharge patterns of lateral superior olive (LSO) neuron responses to monaural and binaural stimuli. The model's geometry was based on morphological data, and static electric properties of the model agree with available intracellular responses to hyperpolarizing current pulses. Inhibitory synapses were located on the soma and excitatory ones on the dendrites, which were modeled as passive cables. The active properties of the model were adjusted to agree with statistical measures derived from extracellular recordings. Calcium-dependent potassium channels supplemented the usual Hodgkin-Huxley characterization for the soma to produce observed serial interspike interval dependence characteristics. Intracellular calcium concentration is controlled by voltage- and calcium-dependent potassium channels and by calcium diffusion and homeostatic mechanisms. By adjusting the density of the calcium-dependent potassium channels, we could span the observed range of transient response patterns found in different LSO neurons. Inputs from the two ears were modeled as Poisson processes to describe the responses to tone-burst stimuli. Transient and sustained responses to monaural and binaural tone-burst stimuli over a wide range of stimulus conditions could be well described by varying only the model's inputs. As found in recordings, model responses having similar discharge rates but different binaural stimulus combinations exhibited differences in interval statistics.

Neuron types in the rat lateral superior olive and developmental changes in the complexity of their dendritic arbors

The lateral superior olive (LSO), a conspicuous mammalian brainstem nucleus that is involved in sound localization, has become a model system for investigating the formation of topographically organized inhibitory and excitatory connections. In experiments employing intracellular injections of Lucifer yellow or neurobiotin into lightly fixed brain slices, we have examined the soma-dendritic morphology of 483 LSO neurons of rats between postnatal day (P) 4 and P36. A detailed analysis of the shape and complexity of dendritic arbors was performed in 238 neurons in order to identify different cell classes and to determine whether age-related changes occur that may relate to a topographical refinement. Regardless of age, seven classes of LSO neurons were identified, more than had been delineated previously with the Golgi technique. Bipolar neurons and multipolar neurons comprised the two major cell types, whereas small multipolar cells, banana-like cells, bushy cells, unipolar cells, and marginal cells were found less frequently. Age-related changes were analyzed in bipolar and multipolar neurons, and several modifications of their dendritic arbors were observed that are in accordance with a refinement of topography. For example, at P4, bipolar and multipolar cells had relatively broad dendritic arbors, with an average of 140 and 138 dendritic end branches, respectively. During further development, their numbers became drastically reduced by about 80%, such that an average of less than 30 endpoints remained by P36. As the dendritic arbors became smaller specifically along the transverse axis of the LSO, they became confined to a smaller frequency area. We conclude from our results that considerable remodeling takes place in the LSO and that the selective loss of dendritic branches may be a morphological correlate for the formation of exquisite tonotopy.

Neuron types in the rat lateral superior olive and developmental changes in the complexity of their dendritic arbors

The lateral superior olive (LSO), a conspicuous mammalian brainstem nucleus that is involved in sound localization, has become a model system for investigating the formation of topographically organized inhibitory and excitatory connections. In experiments employing intracellular injections of Lucifer yellow or neurobiotin into lightly fixed brain slices, we have examined the soma-dendritic morphology of 483 LSO neurons of rats between postnatal day (P) 4 and P36. A detailed analysis of the shape and complexity of dendritic arbors was performed in 238 neurons in order to identify different cell classes and to determine whether age-related changes occur that may relate to a topographical refinement. Regardless of age, seven classes of LSO neurons were identified, more than had been delineated previously with the Golgi technique. Bipolar neurons and multipolar neurons comprised the two major cell types, whereas small multipolar cells, banana-like cells, bushy cells, unipolar cells, and marginal cells were found less frequently. Age-related changes were analyzed in bipolar and multipolar neurons, and several modifications of their dendritic arbors were observed that are in accordance with a refinement of topography. For example, at P4, bipolar and multipolar cells had relatively broad dendritic arbors, with an average of 140 and 138 dendritic end branches, respectively. During further development, their numbers became drastically reduced by about 80%, such that an average of less than 30 endpoints remained by P36. As the dendritic arbors became smaller specifically along the transverse axis of the LSO, they became confined to a smaller frequency area. We conclude from our results that considerable remodeling takes place in the LSO and that the selective loss of dendritic branches may be a morphological correlate for the formation of exquisite tonotopy. J. Comp. Neurol. 390:20–40, 1998. © 1998 Wiley-Liss, Inc.

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.

Input from the medial nucleus of trapezoid body to an interaural level detector

The medial nucleus of the trapezoid body (MNTB) contains components of a neural network that functions as an interaural level difference (ILD) detector. In the cat, lateral superior olivary (LSO) neurons compare the contralateral inhibitory input from the MNTB with an excitatory input from the ipsilateral anteroventral cochlear nucleus to extract information about binaural stimuli. To better specify the inhibitory inputs to the LSO and gain a better understanding of the inhibitory component of the LSO network, the response characteristics of MNTB neurons were examined in cats under stimulus conditions similar to those used to study LSO inhibitory responses. The inhibitory tuning curves of LSO units were wider than the tuning curves of MNTB units. Hence, MNTB neurons with similar, but not identical, characteristic frequencies converge to provide inhibitory input to single LSO neurons. Variations in the number of converging MNTB inputs produced a range of LSO excitatory-inhibitory threshold differences, thus creating a coding mechanism for representing the ILD. Convergence of MNTB inputs also increased the dynamic range over which contralateral stimulus level effects LSO binaural responses beyond the dynamic ranges of individual MNTB units, thus expanding the ILD range encoded by the LSO network. The differences between the first-spike latencies of MNTB and LSO tone burst responses were small and the precision of the LSO first-spike discharges was significantly greater than that of MNTB units. As tone bursts delivered simultaneously to the two ears can consistently inhibit LSO first-spike discharges, the inhibitory input must match the LSO precision by converging a number of the more variably timed MNTB discharges. Because of their precision LSO first-spike discharges may be used to encode interaural time-of-arrival differences of mid- to high-frequency transients. These findings add to the foundation for a comprehensive network model that describes the inputs to the LSO as point processes, delimits the biophysical mechanisms underlying excitatory and inhibitory interactions at the single neuron level, and reveals how these inputs determine the response to different binaural stimulus conditions.

Excitatory and inhibitory response adaptation in the superior olive complex affects binaural acoustic processing

Short-term adaptation was examined in single unit recordings from 113 superior olive neurons of anaesthetized 3- to 6-month-old Long–Evans rats. Responses to an equal intensity BF probe tone presented 1 ms after an ‘adapting’ BF tone were adapted by 56.3±2.6% (mean±S.E.) compared to responses at a 512 ms delay. The rapid decrease in discharge rate during adapting tones often approximated exponential time courses with time constants of less than 20 ms. The recovery from adaptation was exponential with time constants of 106±20.0 ms. The magnitude of adaptation and time course of recovery following monaural stimulation of binaurally excited (EE) neurons were not significantly different in both input pathways. Additionally, in 60% of EE neurons, an ‘adapting’ tone presented to one ear reduced subsequent responses to probe tones presented to the opposite ear. Binaural stimulation resulted in equal or greater adaptation of responses than monaural stimulation of either ear. The recovery of binaural excitatory responses generally followed a time course between recovery functions for ipsilateral and contralateral monaural stimuli. Lateral Superior Olive (LSO) neurons encode sound source location through the interaction of ipsilateral excitation and contralateral inhibition (IE). Ipsilaterally driven excitatory responses in LSO neurons exhibited the greatest magnitude of adaptation (68.5±21.1%). Adaptation of inhibition was observed in over half of IE neurons. Responses of LSO neurons to binaural BF probe stimuli were greatest immediately after a 200 ms BF ‘inhibitory adapting’ stimulus to the contralateral ear, and decreased with greater interstimulus delays. Responses to binaural stimulation were constant after prior binaural adaptation, when the magnitude and recovery of adaptation to monaural stimuli were similar for excitation and inhibition (8/25 IE cells). The functional significance and possible sites of adaptation processes are discussed.

Glycinergic transmission regulates dendrite size in organotypic culture

We previously demonstrated that inhibitory synaptic transmission influences dendrite development in vivo. We now report an analogous finding in an organotypic culture of a glycinergic projection nucleus, the medial nucleus of the trapezoid body (MNTB), and its postsynaptic target, the lateral superior olive (LSO) of gerbils. Cultures were generated at 6-7 days postnatal and grown in serum containing medium with or without the glycine receptor antagonist, strychnine (SN), at 2 microM. LSO neurons were then labeled with biocytin, and the dendritic arbors were analyzed morphometrically. Compared to neurons form age-matched in vivo tissue, the neurons cultured in control media were somewhat atrophic, including decreases in dendritic branching and length. Incubation in strychnine led to a dramatic increase in dendritic branching and total dendritic length. Control neurons averaged 6.3 branches compared to 18 branches/neuron in SN-treated cultures. There was a similar increase in primary dendrites and total dendritic length. The physical elimination of MNTB cells did not mimic SN treatment, presumably because glycinergic LSO neurons generated intrinsic connections. In fact, the LSO soma area was significantly greater following MNTB removal, suggesting that these afferents provide a second signal to postsynaptic neurons. These results suggest that spontaneous glycinergic transmission regulates the growth of postsynaptic processes.

Crossed projection neurons are generated prior to uncrossed projection neurons in the lateral superior olive of the rat

The present study examined in the lateral superior olive (LSO) of the rat whether LSO neurons projecting to the ipsilateral inferior colliculus (IC) might be generated later than those projecting to the contralateral IC. Rat fetuses were exposed in utero to 5-bromodeoxyuridine (BrdU), a thymidine analogue, to label neurons proliferating at different embryonic stages from day E11 through to E20. Upon reaching adulthood, the rats were given unilateral injections of fluoro-gold (FG), a retrograde fluorescent tracer, into the IC. Subsequently, the tissue sections of the brains obtained from the rats were immunostained for BrdU to simultaneously detect neurons that were BrdU-positive and/or FG-positive. BrdU-positive LSO neurons were found in the rats which had been exposed to BrdU during E12–E16. In E12 and E13 BrdU-exposure cases, the vast majority of double-labeled (BrdU-positive and FG-positive) neurons were seen on the contralateral side to the FG injection. In E14, E15 and E16 BrdU-exposure cases, in contrast, all double-labeled neurons were found on the ipsilateral side to the FG injection. The distribution of these double-labeled neurons within the nucleus was diffuse in all the BrdU-exposure cases. Thus, the results indicate that LSO neurons are generated during E12–E16, that the crossed projection neurons are generated 1–4 days earlier than the uncrossed projection neurons, and that no topographical relationships exist between the early- and the late-generated populations of the LSO neurons.

Developmental influence of glycinergic transmission: regulation of NMDA receptor-mediated EPSPs

The influence of excitatory transmission on postsynaptic structure is well established in developing animals, but little is known about the role of synaptic inhibition. We addressed this issue in developing gerbils with two manipulations designed to decrease glycinergic transmission in an auditory nucleus, the lateral superior olive (LSO), before the onset of sound-evoked activity. First, contralateral cochlear ablation functionally denervated the glycinergic pathway from the medial nucleus of the trapezoid body (MNTB) to the LSO, while leaving the excitatory pathway intact. Second, continuous release of a glycine receptor antagonist, strychnine (SN), was used to decrease transmission. The strength of excitatory and inhibitory synapses was examined with whole-cell recordings from LSO neurons in a brain-slice preparation. The percentage of LSO neurons exhibiting MNTB-evoked IPSPs was reduced in both ablated and SN-treated animals. In those neurons displaying IPSPs, the amplitude was significantly reduced. This decrease was accompanied by an 8 mV depolarization in the IPSP equilibrium potential. In contrast, the ipsilaterally evoked EPSPs were of unusually long duration in experimental animals. These long-duration EPSPs were significantly shortened by hyperpolarizing the neuron to -90 mV or exposing them to aminophosphonopentanoic acid (AP-5), an NMDA receptor antagonist. Membrane hyperpolarization and AP-5 had little effect in control neurons. In addition, LSO neurons from ablated or SN-treated animals displayed broad rebound depolarizations after membrane hyperpolarization, and these were abolished in the presence of Ni2+. Because both cochlear ablation and SN-rearing were initiated before the onset of sound-evoked activity, the results suggest that spontaneous glycinergic transmission influences the development of postsynaptic properties, including the IPSP reversal potential, NMDA receptor function, and a Ca2+ conductance.

Synaptically evoked prolonged depolarizations in the developing auditory system.

1. Although synaptic transmission is known to influence many aspects of neuronal development, activity rates are quite low at early ages. The present study describes a long-lasting postsynaptic response to brief periods of synaptic stimulation that may underlie such an influence. Whole-cell patch clamp recordings were made from the lateral superior olive (LSO) in a brain slice preparation from early postnatal gerbils. 2. Stimulation of the excitatory afferent pathway from the cochlear nucleus elicited a prolonged depolarization (PD) in approximately 60% of the LSO neurons tested. Low frequency stimulation (1 Hz) was as effective as tetanic stimulation in producing PDs. These synaptically evoked depolarizations ranged in amplitude from 3 to 32 mV and recovered spontaneously after 0.5-35 min. 3. The LSO neuron input resistance declined during every PD episode and remained significantly lower even after the membrane potential had recovered. These PDs were partially reversed by 2 mM Ni(+2), but 1 microM tetrodotoxin and 10 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) were ineffective. The metabotropic glutamate receptor agonist, trans-1-aminocyclopentane-1,3-dicarboxylic acid (40 microM), produced depolarizations that outlasted the exposure period by an average of 20 min and were also partially repolarized by 2 mM Ni(+2). In contrast, the depolarizations produced by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid or N-methyl-D-aspartate decayed within a much shorter period of time. 4. To test whether in vivo discharge rates are, in fact, very low during development, spontaneous activity was recorded from neurons of the auditory midbrain in gerbils before and during the onset of sound-evoked responses. The average discharge rate of auditory neurons was quite low (X = 0.4 spikes/s), although many cells displayed brief periods of rapid discharge rate (X = 37 spikes/ s). Together, these results demonstrate a novel form of developmental plasticity elicited by low rates of glutamatergic transmission that may involve a metabotropic pathway and prolonged calcium influx.

Decreased inhibition to lateral superior olive neurons in young and aged Sprague-Dawley rats

Lateral superior olive (LSO) neurons in young and aged Sprague-Dawley rats have functional properties consistent with a limited contralateral inhibition, which is markedly different from other animals. An unusually low proportion of LSO cells ( 36 113 ) exhibited contralateral inhibition (and ipsilateral excitation, IE), while over 25% of LSO units exhibited excitatory responses to contralateral stimuli. Inhibition of most IE LSO neurons was evident only when the contralateral intensity was greater than the ipsilateral intensity, resulting in a marked shift in sensitivity to interaural intensity differences (IID). The firing rate of IE neurons was also affected more by a change in intensity of ipsilateral compared to contralateral stimuli. The shift in the IID sensitivity and the relative decrease in effectiveness of contralaterally driven inhibition in Sprague-Dawley rat LSO neurons could be due to decreased inhibitory inputs from the MNTB principal cells, increased contralateral excitatory effects and/or increased ipsilateral excitatory effects. Age-related decreases in the numbers of MNTB neurons observed anatomically is not reflected in a change in LSO function. The Sprague-Dawley rat may be a useful model for the effect of reduced inhibition in the superior olivary complex on auditory behavior.

Lateral superior olive projections to the inferior colliculus in normal and unilaterally deafened ferrets

We have examined the projection from the lateral superior olive (LSO) to the inferior colliculus (IC) in the ferret, with particular interest in the laterality of the projection and in the effects of unilateral cochlear removal in infancy. Large or small deposits of the retrograde tracer wheat germ agglutinin-horseradish peroxidase (WGA-HRP) were made in the IC of anesthetized adult ferrets that either were normally hearing or had been unilaterally deafened in infancy (P5 or P25). After 2 days, the ferrets were perfused, and frontal sections of the brainstem were treated with tetramethyl benzidine. For large deposits of WGA-HRP, equal numbers of labelled neurons were found evenly spread through both LSOs. Smaller deposits of WGA-HRP produced four results that contrasted with previous reports on the cat. First, many more labelled neurons were found in the contralateral than in the ipsilateral LSO. Second, the relative number of labelled neurons in each LSO was independent of whether the deposits were in the ventral or in the dorsal IC. Third, the total number of labelled LSO neurons was independent of whether the deposits were in the ventral or in the dorsal IC. Fourth, the proportion of ipsilateral to contralateral labelled neurons was slightly higher in the medial LSO than in the lateral LSO. Ventral IC deposits resulted in more labelled neurons in the medial LSO, and dorsal IC deposits resulted in more labelled neurons in the lateral LSO, as expected. Neonatal cochlear removal did not change any of these results. We conclude that, in the ferret, the organization of the crossed and uncrossed projections from the LSO to the IC differs from that of the cat, and any similarity with the optic chiasm is not obvious.

Inhibition in the superior olivary complex: pharmacological evidence from mouse brain slice

1. The effects of gamma-aminobutyric acid (GABA) and glycine and their respective antagonists were determined for neurons in the mouse superior olivary complex. Brain slices (400 microns) were cut in the frontal plane and maintained in an oxygenated saline solution for physiological recording. Recordings were made from neurons in the lateral superior olive (LSO) or medial nucleus of the trapezoid body (MNTB) with glass micropipettes filled with 4 M potassium acetate. 2. Ipsilateral and contralateral synaptic responses were elicited by applying current pulses to the trapezoid body through bipolar stimulating electrodes located at positions lateral and medial to the olivary complex. Both intracellular and extracellular recordings were studied before, during, and after application of drugs to the saline bath containing the tissue slice. 3. Intracellular recordings from 10 neurons in LSO showed that GABA (1-10 mM) caused a concentration-dependent drop in membrane resistance and either reduced or blocked postsynaptic excitatory responses. Similar effects were found in five cells tested with glycine (1-10 mM). Three neurons tested with both GABA and glycine were affected by both drugs. Extracellular spikes were blocked in 53 out of 67 LSO neurons tested with GABA and 29 out of 35 neurons tested with glycine. Seventeen out of 23 neurons tested with both GABA and glycine were affected by both. 4. GABA had a powerful blocking effect on extracellularly recorded action potentials evoked by current-pulse stimulation of the trapezoid body in seven LSO neurons tested after adding the glycine receptor antagonist, strychnine (1 microM), to the bath. GABA also lowered the membrane resistance of one LSO neuron in which intracellular recordings were made in the presence of strychnine. 5. Neurons in MNTB also were affected by GABA and glycine but the proportion of sensitive cells was less than in LSO. GABA reduced membrane resistance in 6 out of 16 neurons and glycine produced a similar effect in 14 out of 26 neurons from which intracellular recordings were made. Six out of 14 neurons tested with GABA and glycine responded to both. Extracellular spikes were eliminated or reduced in amplitude by GABA in 15 out of 44 cells and by glycine in 40 out of 68 cells tested. Eleven out of 29 cells from which extracellular recordings were made were affected by both. 6. The glycine antagonist, strychnine (0.25 - 1.0 muM), blocked both ipsilateral and contralateral inhibitory postsynaptic potentials (IPSPs) in LSO.(ABSTRACT TRUNCATED AT 400 WORDS)

A nonstationary Poisson point process describes the sequence of action potentials over long time scales in lateral-superior-olive auditory neurons

The behavior of lateral-superior-olive (LSO) auditory neurons over large time scales was investigated. Of particular interest was the determination as to whether LSO neurons exhibit the same type of fractal behavior as that observed in primary VIII-nerve auditory neurons. It has been suggested that this fractal behavior, apparent on long time scales, may play a role in optimally coding natural sounds. We found that a nonfractal model, the nonstationary dead-time-modified Poisson point process (DTMP), describes the LSO firing patterns well for time scales greater than a few tens of milliseconds, a region where the specific details of refractoriness are unimportant. The rate is given by the sum of two decaying exponential functions. The process is completely specified by the initial values and time constants of the two exponentials and by the dead-time relation. Specific measures of the firing patterns investigated were the interspike-interval (ISI) histogram, the Fano-factor time curve (FFC), and the serial count correlation coefficient (SCC) with the number of action potentials in successive counting times serving as the random variable. For all the data sets we examined, the latter portion of the recording was well approximated by a single exponential rate function since the initial exponential portion rapidly decreases to a negligible value. Analytical expressions available for the statistics of a DTMP with a single exponential rate function can therefore be used for this portion of the data. Good agreement was obtained among the analytical results, the computer simulation, and the experimental data on time scales where the details of refractoriness are insignificant.(ABSTRACT TRUNCATED AT 250 WORDS)

Response of neurons in the lateral superior olive and medial nucleus of the trapezoid body to repetitive stimulation: Intracellular and extracellular recordings from mouse brain slice

The responses of neurons in the lateral superior olive (LSO) and medial nucleus of the trapezoid body (MNTB) to repeated electrical stimulation of the trapezoid body were investigated in a brain slice preparation of the mouse superior olivary complex. Brain slices, 400–500 μm thick, were cut in the frontal plane and were maintained for physiological recording in a bath of warm, oxygenated saline. Both intracellular and extracellular recordings were made with glass micropipettes filled with 4 M potassium acetate. Bipolar stimulating electrodes were placed on the trapezoid body ipsilateral and contralateral to the superior olive. Current levels were set so that an ipsilateral pulse elicited a single action potential in LSO and a contralateral pulse elicited a single action potential in MNTB. Trapezoid body fibers were then stimulated with trains consisting of 10 current pulses. Repeated stimulation at low rates resulted in a number of spikes equal to the number of current pulses. Pulse rate was then increased to determine the limits of response to repeated stimulation. In the MNTB, neurons were capable of following very high rates of stimulation without reduction in response probability. On the average. MNTB neurons responded with a probability of 0.9 at 667 Hz. In contrast, most LSO neurons were incapable of following high rates of stimulation. LSO neurons responded with a probability of 0.9 at 125 Hz. For some LSO neurons, application of strychnine (0.5 μM) to the bath increased the probability of firing at high rates. MNTB neurons were unaffected by strychnine.

Transient appearance of calbindin-D28k-positive neurons in the superior olivary complex of developing rats.

Calbindin-D28k (CaBP) is a calcium-binding protein that is prominent in various parts of the mammalian auditory system. In order to shed some light on the possible role of CaBP during ontogeny, when calcium ions play key roles in several processes, the location of CaBP was examined immunocytochemically in the auditory system of the developing rat. This study focuses on the principal nuclei of the superior olivary complex, which show distinct CaBP labeling in the adult. Consistent with previous reports in the rat and other mammals, CaBP immunoreactivity in adults was intense in somata of the medial nucleus of the trapezoid body (MNTB) and in the neuropil (presumably in axons) of the lateral superior olive (LSO), the superior paraolivary nucleus (SPN), and the medial superior olive (MSO). In fetal and neonatal animals, however, the labeling pattern was strikingly different. Around birth, MNTB neurons are immunonegative for CaBP, whereas somata and processes in the LSO, probably neuronal, are heavily labeled at that age. This labeling pattern persists throughout the first week of postnatal life and begins to change at P8, when MNTB neurons become immunopositive for CaBP. During the next 10 days labeling intensity in MNTB neurons increases considerably, and the increase is paralleled by an increase in labeling intensity of the neuropil in the LSO, SPN, and MSO, indicating that the labeled processes in these nuclei may be axons originating from MNTB neurons. Immunoreactivity in LSO cells begins to decline around P8, decays rapidly between P10 and P18, and reaches its adult level around P28, when the CaBP labeling pattern in the whole superior olivary complex is indistinguishable from that in the adult. The present results show that the development of CaBP immunoreactivity in the rat superior olivary complex is characterized by two reciprocally related processes: as immunoreactivity within MNTB somata and fibers in the SPN, and LSO, and the MSO increases between P8 and about P21, the immunoreactivity in LSO neurons declines. CaBP immunoreactivity in LSO neurons is only transiently present, suggesting a critical period in development during which the control of Ca2+ homeostasis in LSO neurons may be of particular importance.

Response properties in young and old Fischer-344 rat lateral superior olive neurons: A quantitative approach

Significant age-related functional deficits may result from a selective loss of inhibitory processing in the lateral superior olivary (LSO) nucleus. To test this hypothesis, methods were developed for quantitative comparisons of the excitation evoked by ipsilateral acoustic stimuli and the inhibition evoked by contralateral acoustic stimuli in neurons recorded from this binaural structure. Data were obtained from 103 LSO neurons from 22 young adult (3–6 month) and 70 LSO neurons from 14 old (20–23 month) Fischer-344 (F-344) rats. Age-related increases in the thresholds of auditory brainstem responses as well as in the inhibitory and excitatory responses of LSO neurons were observed. Spike-discharge rates were analyzed using multiple regression analysis for interaural intensity data and by calculating correlation coefficients between excitatory and inhibitory isointensity curves. Most LSO principal cells exhibited ipsilateral excitation and contralateral inhibition of similar strength for similar stimuli. Inhibitory and excitatory response areas of these neurons were similar based on visual inspection and correlation coefficients. No statistically significant age-related changes were observed for (a) rate-level functions generated by ipsilateral or contralateral stimuli; (b) maximal discharge rate; (c) conduction latencies; or (d) measures of binaural function. However, a small percentage of LSO neurons both in young and old rats displayed “unmatched” inhibitory and excitatory response areas. Quantitative methods developed in this study are used to examine age-related changes in binaural function in the inferior colliculus of F-344 rats and in the LSO of the Sprague-Dawley rat. Although no asymmetrical aging changes were observed for the F-344 rat LSO, there appear to be significant differences between the aging auditory system in the F-344 and Sprague-Dawley rats. Age-related changes have been previously described for the F-344 in other brainstem auditory structures.