Binaural processing in the dorsal nucleus of the lateral lemniscus

We studied the binaural properties of 72 neurons in the dorsal nucleus of the lateral lemniscus (DNLL) of the mustache bat. There are six main findings: 1) Conventional EI neurons that were excited by stimulation of the contralateral ear and inhibited by ipsilateral stimulation, comprise the majority (80%) of binaural DNLL cells. 2) For most EI neurons the quantitative features of their interaural intensity disparity (IID) functions, maximum inhibition, dynamic range and 50% point IIDs, were largely unaffected by the absolute intensity at the contralateral ear. 3) Although the net effect of the inhibition evoked by ipsilateral stimulation was to suppress discharges evoked by contralateral stimulation, our results indicate that the inhibitory inputs can act in three different ways. The first was a time-intensity trade, where increasing the intensity at the ipsilateral ear evoked inhibitory effects with progressively shorter latencies. The second way was that the latency of inhibition did not appear to decrease with ipsilateral intensity, but rather increasing ipsilateral intensity appeared only to increase the strength of the inhibition. The third way was that the lowest effective ipsilateral intensity suppressed the first spikes evoked by the contralateral stimulus and higher ipsilateral intensities then suppressed the later discharges of the train. Each of these inhibitory patterns was seen in about a third of the cells. 4) Neurons that had more complex binaural properties, such as the facilitated EI neurons (EI/F) and neurons that were driven by sound to either ear (EE neurons), represented about 20% of the binaural population. There were two types of EE neurons; those in which there was a simple summation of discharges evoked with certain IIDs, and those in which the spike-counts to binaural stimulation at certain IIDs were greater than a summation of the monaural counts and thus were facilitated. 5) All binaural neurons were strongly inhibited with IIDs that favored the ipsilateral ear. Our findings indicate that the more complex binaural types, the facilitated EI neurons (EI/F) as well as the two types of EE neurons, may be constructed from conventional EI neurons by adding inputs from several sources that impart the more complex features to these neurons. We propose four circuits that could account for the different binaural response properties that we observed. The circuits are based on the known connections of the DNLL and the neurochemistry of those connections. Finally, we compared the binaural properties of neurons in the mustache bat DNLL with those of neurons in the mustache bat inferior colliculus and lateral superior olive.(ABSTRACT TRUNCATED AT 400 WORDS)     

Modeling of percutaneous drug transport in vitro using skin-imitating Carbosil membrane

Extracellular recordings were made with microelectrodes from single neurons in the rat's dorsal nucleus of the lateral lemniscus (DNLL) and response characteristics were determined for monaural and binaural acoustic stimulation. The vast majority of DNLL neurons were narrowly tuned to sound frequency and their temporal responses to contralateral tone pulses fell into one of three broad categories: onset (57%), sustained (21%) or onset-pause-sustained (22%). Most DNLL neurons fired multiple action potentials to a single click delivered to the contralateral ear. The majority (77%) of DNLL neurons showed a monotonic increase in the number of spikes elicited by contralateral tone pulses of increasing sound pressure level; the remaining cells were weakly non-monotonic. No obvious tonotopic pattern was found in the distribution of characteristic frequency of neurons in DNLL. Most DNLL neurons exhibited either excitatory/inhibitory (74%) or excitatory/excitatory (9%) binaural response patterns. The remaining cells (17%) were monaural and driven exclusively by stimulation of the contralateral ear. The binaural neurons in DNLL were sensitive to both interaural intensity and interaural time differences as determined by presentation of dichotic tone bursts and clicks respectively. The responses of DNLL neurons could be distinguished on the basis of monaural and binaural response characteristics from those in surrounding areas including the sagulum, paralemniscal zone and the intermediate nucleus of the lateral lemniscus.     

Binaural inhibition is important in shaping the free-field frequency selectivity of single neurons in the inferior colliculus

1. We have shown previously that under free-field stimulation in the frontal field, frequency selectivity of the majority of inferior colliculus (IC) neurons became sharper when the loudspeaker was shifted to ipsilateral azimuths. These results indicated that binaural inhibition may be responsible for the direction-dependent sharpening of frequency selectivity. To test the above hypothesis directly, we investigated the frequency selectivity of IC neurons under several conditions: monaural stimulation using a semiclosed acoustical stimulation system, binaural stimulation dichotically also using a semiclosed system, free-field stimulation from different azimuths, and free-field stimulation when the ipsilateral ear was occluded monaurally (coated with a thick layer of petroleum jelly, which effectively attenuated acoustic input to this ear). 2. The binaural interaction pattern of 98 IC neurons of northern leopard frogs (Rana pipiens pipiens) were evaluated; of these neurons, there were 34 EE and 64 EO neurons. The majority of IC neurons (92 of 98) showed some degree of binaural inhibition (i.e., showing diminished response when the ipsilateral and contralateral ears were stimulated simultaneously) whether they were designated as EE or EO; these IC neurons thus were classified as EE-I or EO-I. Neurons were classified as exhibiting strong inhibition if the ILD function showed a pronounced response decrement, i.e., a decrease of > or = 50% of the response to monaural stimulation of the contralateral ear. Those neurons that showed smaller response decrements (decrease was > or = 25% but < 50%) were designated as showing weak inhibition. Most of these EE-I and EO-I neurons (n = 68) showed strong binaural inhibition. 3. In agreement with results from our earlier studies, frequency threshold curves (FTCs) of IC neurons were altered by sound azimuth. Independent of binaural interaction pattern, most IC neurons (59 of 98) showed a narrowing of the FTC as sound direction was changed from contralateral 90 deg (c90 degrees) to ipsilateral 90 deg (i90 degrees). IC neurons that exhibited the largest direction-dependent changes in frequency selectivity were typically those that displayed stronger binaural inhibition. Occlusion of the ipsilateral ear, which reduced the strength of binaural inhibition by this ear, abolished direction-dependent frequency selectivity. 4. FTCs of IC neurons that exhibited little to moderate direction-dependent effects on frequency selectivity were associated typically with neurons that displayed weak binaural inhibition. Associated with this weak binaural inhibition, central neural responses under monaural occlusion also displayed only small effects; the FTCs were only slightly broader than those derived in the intact condition, and as before, the experimental manipulation resulted in abolishment of direction-dependent frequency selectivity. 5. In contrast to most IC neurons, which showed direction-dependent narrowing of the FTC, about one-third (34 of 98) of IC neurons studied showed a broadening of the FTC when sound direction was shifted to ipsilateral azimuths. Interestingly, for 90% of these 34 neurons, monaural occlusion resulted in narrowing of the bandwidth at each azimuth instead of broadening of the FTC bandwidth. We have evidence to suggest that this direction-dependent broadening is actually a consequence of a truncation or loss of the tip of the FTC derived at c90 degrees, which results from strong binaural inhibition. 6. To compare the frequency threshold tuning in response to monaural stimulation of each ear with free-field FTCs, we measured FTCs for each of the 34 EE neurons to independent contralateral and ipsilateral stimulation. FTCs derived from ipsilateral monaural stimulation were significantly narrower than those resulting from contralateral monaural stimulation, independent of a neuron's direction-dependent changes in frequency selectivity.     

Single unit activity in the inferior colliculus of the rat elicited by electrical stimulation of the cochlea

The activity of single neurons (n = 182) of the central nucleus of the inferior colliculus (CIC) of the rat was recorded in response to unilateral electrical stimulation of the left cochlea and/or acoustical stimulation of the right ear. The probability of response to both modes of stimulation was comparable (90 per cent for contralateral and 60 per cent for ipsilateral presentation). Response patterns consisted predominantly of onset excitations. Response latencies to electrical stimuli ranged from 3 to 21 ms, with an average value of 9.7 ms (SD = 3.5 ms) in the ipsilateral CIC and 6.6 ms (SD = 3.4 ms) in the contralateral CIC. With respect to binaural inputs, the majority of units were excited by stimulation of either ear (EE; about 60 per cent) while about one third were influenced by one ear only (EO). Units excited by one ear and inhibited by the other (EI) were rare. The main difference between the present implanted rats and normal animals was the virtual absence here of inhibitory effects for both types of stimuli when they were delivered to the ipsilateral ear (very few EI units).     

Response properties of neurons in the inferior colliculus of the monaurally deafened ferret to acoustic stimulation of the intact ear

Response properties of neurons in the central nucleus of the inferior colliculus (ICC) were investigated after unilateral cochlear removal at various ages during infancy. Nineteen ferrets had the right cochlea surgically ablated, either in adulthood or on postnatal day (P) 5, 25, or 40, 3-18 mo before recording. Adult ablations were made on the same day as ("acute," n = 3), or 2-3 mo before ("chronic," n = 3), recording. Two ferrets were left binaurally intact. Single-unit (n = 702) and multiunit (n = 1,819) recordings were made in the ICC of barbiturate-anesthetized ferrets ipsilateral (all ages) or contralateral (P5 and acute adult only) to the intact ear. In binaurally intact animals, tonal stimulation of the contralateral ear evoked excitatory activity at the majority (94%) of recording loci, whereas stimulation of the ipsilateral ear evoked activity at only 33% of recording loci. In acutely ablated animals, the majority of contralateral (90%) and ipsilateral (70%) loci were excited by tonal stimulation of the intact ear. In chronically ablated animals, 80-90% of loci were excited by ipsilateral stimulation. Single-unit thresholds were generally higher for low-best frequency (BF) than for high-BF units, and higher in the ipsilateral than in the contralateral ICC. Analysis of covariance showed highly significant differences between all of the ipsilateral and contralateral groups, but no effects of age at ablation or survival time following ablation, other than that the group ablated at P25 had higher mean ipsilateral thresholds than the groups ablated at P5 or, acutely, in adulthood. Cochlear ablation at P5, 25, or 40 resulted in a significant increase in dynamic ranges of ipsilateral ICC unit rate-intensity functions relative to acutely ablated animals. Dynamic ranges of units in the contralateral ICC of P5-ablated ferrets were also significantly increased compared with those of acutely ablated animals. Cochlear ablation at P5, 25, or 40 resulted in a significant increase in single-unit spontaneous discharge rates in the ICC ipsilateral but not contralateral (P5 only) to the intact ear. These data show that unilateral cochlear removal in adult ferrets leads to a rapid and dramatic increase in the proportion of neurons in the ICC ipsilateral to the intact ear that is excited by acoustic stimulation of that ear. In addition, the data confirm that, in ferrets, cochlear removal in infancy leads to a further increase in responsiveness of individual neurons in the ipsilateral ICC. Finally, the data show that responses in the ICC contralateral to the intact ear are largely but not completely unchanged by unilateral cochlear removal.     

Time course of forward masking tuning curves in cat primary auditory cortex

Nonsimultaneous two-tone interactions were studied in the primary auditory cortex of anesthetized cats. Poststimulatory effects of pure tone bursts (masker) on the evoked activity of a fixed tone burst (probe) were investigated. The temporal interval from masker onset to probe onset (stimulus onset asynchrony), masker frequency, and intensity were parametrically varied. For all of the 53 single units and 58 multiple-unit clusters, the neural activity of the probe signal was either inhibited, facilitated, and/or delayed by a limited set of masker stimuli. The stimulus range from which forward inhibition of the probe was induced typically was centered at and had approximately the size of the neuron's excitatory receptive field. This "masking tuning curve" was usually V shaped, i.e., the frequency range of inhibiting masker stimuli increased with the masker intensity. Forward inhibition was induced at the shortest stimulus onset asynchrony between masker and probe. With longer stimulus onset asynchronies, the frequency range of inhibiting maskers gradually became smaller. Recovery from forward inhibition occurred first at the lower- and higher-frequency borders of the masking tuning curve and lasted the longest for frequencies close to the neuron's characteristic frequency. The maximal duration of forward inhibition was measured as the longest period over which reduction of probe responses was observed. It was in the range of 53-430 ms, with an average of 143 +/- 71 (SD) ms. Amount, duration and type of forward inhibition were weakly but significantly correlated with "static" neural receptive field properties like characteristic frequency, bandwidth, and latency. For the majority of neurons, the minimal inhibitory masker intensity increased when the stimulus onset asynchrony became longer. In most cases the highest masker intensities induced the longest forward inhibition. A significant number of neurons, however, exhibited longest periods of inhibition after maskers of intermediate intensity. The results show that the ability of cortical cells to respond with an excitatory activity depends on the temporal stimulus context. Neurons can follow higher repetition rates of stimulus sequences when successive stimuli differ in their spectral content. The differential sensitivity to temporal sound sequences within the receptive field of cortical cells as well as across different cells could contribute to the neural processing of temporally structured stimuli like speech and animal vocalizations.     

Crossed and direct effects of digital nerves stimulation on motor evoked potential: a study with magnetic brain stimulation

We studied the influence of contralateral and ipsilateral cutaneous digital nerve stimulation on motor evoked potentials (MEPs) elicited in hand muscles by transcranial magnetic stimulation (TMS). We tested the effect of different magnetic stimulus intensities on MEPs recorded from the thenar eminence (TE) muscles of the right hand while an electrical conditioning stimulus was delivered to the second finger of the same hand with an intensity four times above the sensory threshold. Amplitude decrement of conditioned MEPs as a function of magnetic stimulus intensity was observed. The lowest TMS stimulus intensity produced the largest decrease in conditioned MEPs. Moreover, we investigated the effects of ipsilateral and contralateral electrical digital stimulation on MEPs elicited in the right TE and biceps muscle using an intensity 10% above the threshold. Marked MEP inhibition in TE muscles following both ipsilateral and contralateral digital stimulation is the main finding of this study. The decrease in conditioned MEP amplitude to ipsilateral stimulation reached a level of 50% of unconditioned MEP amplitude with the circular coil and 30% with the focal coil. The amplitude of conditioned MEPs to contralateral digital stimulation showed a decrease of 60% with the circular coil and more than 50% with the focal coil. The onset of the inhibitory effect of contralateral stimulation using the focal coil occurred at a mean of 15 ms later than that of ipsilateral stimulation. No MEP inhibition was observed when recording from proximal muscles. Ipsilateral and contralateral digital stimulation had no effect on F wave at appropriate interstimulus intervals, where the main MEP suppression was noted. We stress the importance of selecting an appropriate test stimulus intensity to evaluate MEP inhibition by digital nerves stimulation. Spinal and cortical sites of sensorimotor integration are adduced to explain the direct and crossed MEP inhibition following digital nerves stimulation.     

Isochronic mapping of the auditory brainstem response: normative results

Isochronic mapping involves recording multi-channel evoked potentials from scalp electrodes and plotting contours of peak latencies. In this study, auditory brainstem responses were recorded from 20 electrode sites for left, right and binaural stimulation of each ear of 10 male and 10 female, normally hearing, young adults. Analysis of the data showed that the stimulus parameters of intensity, polarity and rate had no significant effect on the maps. On monaural stimulation, wave V was recorded first at the contralateral mastoid and ipsilaterally frontally and last at the ipsilateral mastoid some 350, mu s later. Binaural stimulation gave a symmetrical map, with wave V recorded first frontally and last at the occiput. In contrast, wave III was recorded first ipsilaterally and frontally and last at the contralateral mastoid. Wave II was recorded first at the rear of the contralateral mastoid and last forward of the ipsilateral mastoid. Comparisons between these results and human physiological studies are in agreement for waves V and III but do not support the concept of the VIIth nerve alone as the generator for wave II. These results suggest that this technique is a potentially useful diagnostic tool and it is intended to evaluate it by testing patients with a range of sensory, peripheral-neural and central-neural pathologies.     

Amino-terminal identity of co-existent amyloid and non-amyloid immunoglobulin kappa light chain deposits. A human disease to study alterations of protein conformation

The sizes of the motor-evoked potentials (MEPs) and the durations of the silent periods after transcranial magnetic stimulation were examined in biceps brachii, brachioradialis and adductor pollicis in human subjects. Stimuli of a wide range of intensities were given during voluntary contractions producing 0-75% of maximal force (maximal voluntary contraction, MVC). In adductor pollicis, MEPs increased in size with stimulus intensity and with weak voluntary contractions (5% MVC), but did not grow larger with stronger contractions. In the elbow flexors, MEPs grew little with stimulus intensity, but increased in size with contractions of up to 50% of maximal. In contrast, the duration of the silent period showed similar changes in the three muscles. In each muscle it increased with stimulus intensity but was unaffected by changes in contraction strength. Comparison of the responses evoked in biceps brachii by focal stimulation over the contralateral motor cortex with those evoked by stimulation with a round magnetic coil over the vertex suggests an excitatory contribution from the ipsilateral cortex during strong voluntary contractions.     

Expression and epitopic conservation of calponin in different smooth muscles and during development

The synaptic organization of the saccade-related neuronal circuit between the superior colliculus (SC) and the brainstem saccade generator was examined in an awake monkey using a saccadic, midflight electrical-stimulation method. When microstimulation (50-100 microA, single pulse) was applied to the SC during a saccade, a small, conjugate contraversive eye movement was evoked with latencies much shorter than those obtained by conventional stimulation. Our results may be explained by the tonic inhibition of premotor burst neurons (BNs) by omnipause neurons that ceases during saccades to allow BNs to burst. Thus, during saccades, signals originating from the SC can be transmitted to motoneurons and seen in the saccade trajectory. Based on this hypothesis, we estimated the number of synapses intervening between the SC and motoneurons by applying midflight stimulation to the SC, the BN area, and the abducens nucleus. Eye position signals were electronically differentiated to produce eye velocity to aid in detecting small changes. The mean latencies of the stimulus-evoked eye movements were: 7.9 +/- 1.0 ms (SD; ipsilateral eye) and 7.8 +/- 0.9 ms (SD; contralateral eye) for SC stimulation; 4.8 +/- 0.5 ms (SD; ipsilateral eye) and 5.1 +/- 0.7 ms (SD; contralateral eye) for BN stimulation; and 3.6 +/- 0.4 ms (SD; ipsilateral eye) and 5.2 +/- 0.8 ms (SD; contralateral eye) for abducens nucleus stimulation. The time difference between SC- and BN-evoked eye movements (about 3 ms) was consistent with a disynaptic connection from the SC to the premotor BNs.     

Effects of stimulus intensity on signals from human somatosensory cortices

We recorded somatosensory evoked magnetic fields (SEFs) to left median nerve electric stimulation from seven healthy subjects. The stimulus intensity was varied in three sessions: sensory stimuli evoked a clear tactile sensation without any movement, weak motor stimuli exceeded the motor threshold, and strong motor stimuli caused a vigorous movement. Responses were modelled with sources in the contralateral primary somatosensory cortex (SI), the contralateral and ipsilateral secondary somatosensory cortices (SIIs) and the contralateral posterior parietal cortex (PPC). The amplitude of the 20 ms response from the SI cortex and the subjective magnitude estimations followed the stimulus intensity whereas signals from the three other areas saturated already at the level of the motor threshold. The results implicate differential roles for various somatosensory cortices in intensity coding.     

Lateral inhibitory interactions in the intermediate layers of the monkey superior colliculus

The intermediate layers of the monkey superior colliculus (SC) contain neurons the discharges of which are modulated by visual fixation and saccadic eye movements. Fixation neurons, located in the rostral pole of the SC, discharge action potentials tonically during visual fixation and pause for most saccades. Saccade neurons, located throughout the remainder of the intermediate layers of the SC, discharge action potentials for saccades to a restricted region of the visual field. We defined the fixation zone as that region of the rostral SC containing fixation neurons and the saccade zone as the remainder of the SC. It recently has been hypothesized that a network of local inhibitory interneurons may help shape the reciprocal discharge pattern of fixation and saccade neurons. To test this hypothesis, we combined extracellular recording and microstimulation techniques in awake monkeys trained to perform oculomotor paradigms that enabled us to classify collicular fixation and saccade neurons. Microstimulation was used to electrically activate the fixation and saccade zones of the ipsilateral and contralateral SC to test for inhibitory and excitatory inputs onto fixation and saccade neurons. Saccade neurons were inhibited at short latencies following electrical stimulation of either the ipsilateral (1-5 ms) or contralateral (2-7 ms) fixation or saccade zones. Fixation neurons were inhibited 1-4 ms after electrical stimulation of the ipsilateral saccade zone. Stimulation of the contralateral saccade zone led to much weaker inhibition of fixation neurons. Stimulation of the contralateral fixation zone led to short-latency (1-2 ms) excitation of fixation neurons. Only a small percentage of saccade and fixation neurons were activated by the electrical stimulation (latency: 0.5-2.0 ms). These responses were confirmed as either orthodromic or antidromic responses using collision testing. The results suggest that a local network of inhibitory interneurons may help shape not only the reciprocal discharge pattern of fixation and saccade neurons but also permit lateral interactions between all regions of the ipsilateral and contralateral SC. These interactions therefore may be critical for maintaining stable visual fixation, suppressing unwanted saccades, and initiating saccadic eye movements to targets of interest.     

Lateralized auditory spatial perception and the contralaterality of cortical processing as studied with functional magnetic resonance imaging and magnetoencephalography

Functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) were used to study the relationships between lateralized auditory perception in humans and the contralaterality of processing in auditory cortex. Subjects listened to rapidly presented streams of short FM-sweep tone bursts to detect infrequent, slightly deviant tone bursts. The stimulus streams consisted of either monaural stimuli to one ear or the other or binaural stimuli with brief interaural onset delays. The onset delay gives the binaural sounds a lateralized auditory perception and is thought to be a key component of how our brains localize sounds in space. For the monaural stimuli, fMRI revealed a clear contralaterality in auditory cortex, with a contralaterality index (contralateral activity divided by the sum of contralateral and ipsilateral activity) of 67%. In contrast, the fMRI activations from the laterally perceived binaural stimuli indicated little or no contralaterality (index of 51%). The MEG recordings from the same subjects performing the same task converged qualitatively with the fMRI data, confirming a clear monaural contralaterality, with no contralaterality for the laterally perceived binaurals. However, the MEG monaural contralaterality (55%) was less than the fMRI and decreased across the several hundred millisecond poststimulus time period, going from 57% in the M50 latency range (20-70 ms) to 53% in the M200 range (170-250 ms). These data sets provide both quantification of the degree of contralaterality in the auditory pathways and insight into the locus and mechanism of the lateralized perception of spatially lateralized sounds.     

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.     

Discharge properties of Purkinje cells in the oculomotor vermis during visually guided saccades in the macaque monkey

1. We previously described discharge properties of cerebellar output cells in the fastigial nucleus during ipsilateral and contralateral saccades. Fastigial cells exhibited unique responses depending on the direction of saccades and were involved in execution of accurate targeting saccades. Purkinje cells in the oculomotor vermis (lobules VIc and VII) are thought to modulate these discharges of fastigial cells. In this study we reexamine discharge properties of Purkinje cells on the basis of this hypothesis. 2. Initially we physiologically identified the right and left sides of the oculomotor vermis. Saccade-related discharges of 79 Purkinje cells were recorded from both sides of the vermis during visually guided saccades toward the sides ipsilateral and contralateral to the recording side in two trained macaque monkeys. To clarify the correlation of Purkinje cell discharge with burst activities in the fastigial nucleus during saccadic eye movements, we analyzed our data by employing methods used in the study of fastigial neurons. 3. Among the 79 cells, 56 (71%) showed burst discharges during saccades (saccadic burst cells). Of the 56 cells, 29 exhibited a peak of burst discharges in both the contralateral and ipsilateral directions (bidirectional cells). The remaining 27 saccadic burst cells showed a peak of burst discharges during either contralateral or ipsilateral saccades (unidirectional cells). Among the 79 cells, 14 (18%) exhibited a pause of discharges during contralateral saccades (pause cells). Among the 79 cells, 9 (11%) showed burst discharge during contralateral saccades followed by tonic discharge that was correlated with eye position (burst tonic cells). 4. The timing of bursts in bidirectional cells with respect to saccade onset was dependent on the direction of saccade. During ipsilateral saccades, Purkinje cells exhibited a long lead burst that built up gradually, peaked near the onset of the saccade, and terminated sharply near midsaccade. The mean lead time relative to saccade onset was 29.3 +/- 24.5 (SD) ms. During contralateral saccades, Purkinje cells exhibited a short lead/late burst that built up sharply, peaked near midsaccade, and terminated gradually after the end of the saccade. The mean lead time relative to saccade onset was 10.7 +/- 20.8 ms. The burst onset time during contralateral saccades and the burst offset time during ipsilateral saccades preceded the saccade offset time by about the same interval regardless of the saccade amplitude. 5. In pause cells the pause preceded saccade onset by 17.5 +/- 10.6 ms. The duration of the pause was not correlated with the duration of saccades. There was little trial-to-trial variability in the onset time of the pause with respect to the onset of saccades, whereas there was large trial-to-trial variability in the offset time of the pause with respect to the offset of saccades. In addition, the mean onset time of the pause for each cell had a relatively narrow distribution. 6. The burst lead time of burst tonic cells relative to saccade onset was 9.5 +/- 3.9 ms. The tonic discharge rate of burst tonic cells was a nonlinear function of eye position. The regression of each cell was fit to two lines. The regression coefficient ranged from 0.95 to 0.99 (mean = 0.97). 7. Axons of Purkinje cells in the oculomotor vermis are thought to project exclusively to saccadic burst cells in the fastigial oculomotor region (FOR), which is located in the caudal portion of the fastigial nucleus. Our previous studies indicated that FOR cells provide temporal signals for controlling targeting saccades. The present results suggest that Purkinje cells in the oculomotor vermis modify the temporal signals of FOR cells for saccades in different directions and amplitudes. The modification of FOR cell activity by Purkinje cells is thought to be essential for the function of the cerebellum in the control of saccadic eye movements.     

Effect of flow on first-pass metabolism of drugs: single pass studies on 4-methylumbelliferone conjugation in the serially perfused rat intestine and liver preparations

Intracellular in vivo recordings of physiologically identified inferior colliculus central nucleus (ICc) auditory neurons (n = 71) were carried out in anesthetized guinea pigs. The neuronal membrane characteristics are described showing mainly quantitative differences with a previous report [Nelson, P.G. and Erulkar, S.D., J. Neurophysiol., 26 (1963) 908-923]. The spontaneous spike activity was consistent with the discharge pattern of most extracellularly recorded units. The action potentials showed different spike durations, short and long, and some of them exhibited hyperpolarizing post-potentials. There were also differences in firing rate. The ICc neurons exhibited irregular activity producing spike trains as well as long silent periods (without spikes). Intracellular current injection revealed membrane potential adaptation and shifts that outlasted the electrical stimuli by 20-30 ms. Both evoked synaptic potentials and the spike activity in response to click and tone-burst stimulation were analyzed. Depolarizing-hyperpolarizing synaptic potentials were found in response to contralateral and binaural sound stimulation that far outlasted the stimulus (up to 90 ms). When ipsilaterally stimulated, inhibitory responses and no-responses were also recorded. Although few cells were studied, a similar phenomenon was observed using tone-burst stimulation; moreover, a good correlation was obtained between membrane potential shifts and the triggered spikes (input-output relationship). These in vivo results demonstrate the synaptic activity underlying many of the extracellularly recorded discharge patterns. The data are consistent with the known multi-synaptic ascending pathway by which signals arrive at the ICc as well as the descending corticofugal input that may contribute to the generation of long duration post-synaptic potentials.     

Characterization of vestibular potentials evoked by linear acceleration pulses in the chinchilla

The objective of this study was to improve vestibular evoked potentials as a qualitative parameter for vestibular function in small laboratory animals. Linear upward acceleration pulses (up to 8 g within 1 ms) were applied to the head of anesthetized chinchillas. Electrophysiologic responses recorded by a chronically implanted electrode within the facial nerve canal consisted of an initial negative potential, labeled N1, within the first millisecond following the onset of acceleration. This potential was followed by a series of positive and negative potentials found to be highly labile to acoustic masking. The initial negative potential was only minimally sensitive to acoustic masking and persisted following surgical cochlear ablation, but completely disappeared following administration of potassium chloride into the inner ear. Recorded from the contralateral ear, N1 was unaffected by these procedures. Amplitudes of N1 decreased with attenuating stimulus intensity (1.45 microV/dB), whereby N1 latencies slightly increased (-0.015 ms/dB). These data, when coupled with the ability to completely abolish N1 with potassium intoxication while the contralateral ear remained intact, indicate that this potential represents electrophysiologic activity resulting from activation of the ipsilateral vestibular labyrinth.     

Light scattering changes follow evoked potentials from hippocampal Schaeffer collateral stimulation

We assessed relationships of evoked electrical and light scattering changes from cat dorsal hippocampus following Schaeffer collateral stimulation. Under anesthesia, eight stimulating electrodes were placed in the left hippocampal CA field and an optic probe, coupled to a photodiode or a charge-coupled device camera to detect scattered light changes, was lowered to the contralateral dorsal hippocampal surface. Light at 660 +/- 10 (SE) nm illuminated the tissue through optic fibers surrounding the optic probe. An attached bipolar electrode recorded evoked right hippocampal commissural potentials. Electrode recordings and photodiode output were simultaneously acquired at 2.4 kHz during single biphasic pulse stimuli 0.5 ms in duration with 0.1-Hz intervals. Camera images were digitized at 100 Hz. An average of 150 responses was calculated for each of six stimulating current levels. Stimuli elicited a complex population synaptic potential that lasted 100-200 ms depending on stimulus intensity and electrode position. Light scattering changes peaked 20 ms after stimuli and occurred simultaneously with population spikes. A long-lasting light scattering component peaked 100-500 ms after the stimulus, concurrently with larger population postsynaptic potentials. Optical signals occurred over a time course similar to that for electrical signals and increased with larger stimulation amplitude to a maximum, then decreased with further increases in stimulation current. Camera images revealed a topographic response pattern that paralleled the photodiode measurements and depended on stimulation electrode position. Light scattering changes accompanied fast electrical responses, occurred too rapidly for perfusion, and showed a stimulus intensity relationship not consistent with glial changes.     

Middle latency responses to electrical stimulation of the auditory nerve in unanaesthetized guinea pigs

Middle latency responses (MLR) to sinusoidal and pulsatile electrical stimulation (ES) of the cochlea and to acoustical stimulation (AS) were evaluated in awake guinea pigs with chronically implanted electrodes. The ear, which was later electrically stimulated, was deafened by local intracochlear application of gentamicin, the opposite ear was left intact. Waveforms and P1-P2 interpeak intervals of the electrically evoked MLR (ES-MLR) were similar to those evoked by acoustical stimulation of the intact ear (AS-MLR) and the latencies of the ES-MLR were shorter by about 1-3 ms. Thresholds of ES-MLR in the frequency range 0.5-32 kHz increased with increasing ES frequency (slope 3.2 dB/octave), thresholds were 3.5-9.5 dB lower for intracochlear than for extracochlear ES. Dynamic ranges for ES-MLR varied between 6-20 dB. MLR amplitude-intensity functions for ES were steeper (slope 2-12 microV/dB) than those for AS (slope 0.2-2 microV/dB). Maximal ES-MLR amplitudes exceeded usually 1.5-3 times the amplitudes of the acoustically evoked MLR. Both types of stimulations evoked larger MLR amplitudes to contralateral stimulation than to ipsilateral stimulation (average ratio = 4.1 +/- 2.2 for AS and 3.3 +/- 2.2 for ES). Because of the relatively long latency and therefore insensitivity to electrical artifact, the ES-MLR can be used for the evaluation of different strategies of the electrical stimulation of the cochlea in awake guinea pig.     

Sources of GABAergic input to the inferior colliculus of the rat

We have studied the GABAergic projections to the inferior colliculus (IC) of the rat by combining the retrograde transport of horseradish peroxidase (HRP) and immunohistochemistry for gamma-amino butyric acid (GABA). Medium-sized (0.06-0.14 microliter) HRP injections were made in the ventral part of the central nucleus (CNIC), in the dorsal part of the CNIC, in the dorsal cortex (DCIC), and in the external cortex (ECIC) of the IC. Single HRP-labeled and double (HRP-GABA)-labeled neurons were systematically counted in all brainstem auditory nuclei. Our results revealed that the IC receives GABAergic afferent connections from ipsi- and contralateral brainstem auditory nuclei. Most of the contralateral GABAergic input originates in the IC and the dorsal nucleus of the lateral lemniscus (DNLL). The dorsal region of the IC (DCIC and dorsal part of the CNIC) receives connections mostly from its homonimous contralateral region, and the ventral region from the contralateral DNLL. The commissural GABAergic projections originate in a morphologically heterogeneous neuronal population that includes small to medium-sized round and fusiform neurons as well as large and giant neurons. Quantitatively, the ipsilateral ventral nucleus of the lateral lemniscus is the most important source of GABAergic input to the CNIC. In the superior olivary complex, a smaller number of neurons, which lie mainly in the periolivary nuclei, display double labeling. In the contralateral cochlear nuclei, only a few of the retrogradely labeled neurons were GABA immunoreactive. These findings give us more information about the role of GABA in the auditory system, indicating that inhibitory inputs from different ipsi- and contralateral, mono- and binaural auditory brainstem centers converge in the IC.