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Patterns of glutamate, glycine, and GABA immunolabeling in four synaptic terminal classes in the lateral superior olive of the guinea pig.

The goal of this study was to correlate synaptic ultrastructure with transmitter specificity and function in the lateral superior olive (LSO), a nucleus that is thought to play a major role in sound localization. This was accomplished by means of postembedding immunogold immunocytochemistry. Four classes of synaptic terminals were identified in the LSO. They were distinguishable from one another both morphologically and on the basis of their different patterns of immunolabeling for glutamate, glycine, and gamma-aminobutyric acid (GABA). The highest level of glutamate immunoreactivity was found in terminals that contained round vesicles (R) and formed synaptic contacts with asymmetric synaptic junctions. Round-vesicle terminals predominated on small caliber dendrites by a ratio of at least 2:1 over the other classes combined. The thinnest dendrites were typically contacted by R terminals only. The ratio of R terminals to the other types decreased as the caliber of the dendritic profiles they apposed increased so that on the soma, R terminals were outnumbered by at least 2:1 by the other types. Terminals containing flattened vesicles (F) exhibited intense immunoreactivity for both glycine and glutamate, although the glutamate immunolabeling was not as high as that in the R terminals. Flattened-vesicle terminals formed symmetric synaptic contacts with their targets and their distribution was the reverse of that described for R terminals; i.e., they were most abundant on LSO perikarya and fewest on small caliber dendrites. Two terminal types, both containing pleomorphic vesicles and forming symmetric synaptic junctions, were found in far fewer numbers. One group contained large pleomorphic vesicles (LP) and was immunoreactive for both glycine and GABA. The other group contained small pleomorphic vesicles (SP) along with a few dense-core vesicles and labeled for GABA only. The LP terminals were preferentially distributed on somata and large-caliber dendrites, while the SP terminals most often contacted smaller dendrites. Previous work suggests that a large percentage of the R terminals arise from spherical cells in the ipsilateral cochlear nucleus and are excitatory in action. This pathway may use glutamate as a transmitter. Many of the F terminals are thought to originate from the ipsilateral medial nucleus of the trapezoid body and appear to be the inhibitory (glycinergic) terminals from a pathway that originates from the contralateral ear. The origins and functions of LP and SP terminals are unknown, but a few possibilities are discussed along with the significance of cocontainment of neuroactive substances in specific terminal types.

Animals

Responses of neurons in inferior colliculus to variations in sound-source azimuth.

This study aimed to classify the responses of single units in the auditory midbrain to acoustic stimuli presented in the free field in order to characterize those units likely to have a role in sound localization in the horizontal plane. The responses of 131 single units in the inferior colliculus of the cat and the brush-tailed possum were studied using tone and noise-burst stimuli presented from a speaker capable of movement at any point along a plane 10 degrees above the horizontal plane. Speaker positions along this plane are referred to as speaker azimuths; those on the same side as the recorded inferior colliculus as ipsilateral, and on the opposite side as contralateral, azimuths. For each unit, spike counts were measured as a function of azimuth either at the best frequency (BF) or using noise bursts. These functions are referred to as azimuth functions and were usually measured for at least two intensities, between 10 and 70 dB above threshold. The recording sites of most units were identified histologically with the aid of microlesions and were related to the major subdivisions of the inferior colliculus: the central nucleus (ICC), the lateral part of the external nucleus (ICX), and the rostroventral process (R-ICX). Two units were located in the pericentral nucleus and two in the dorsal nucleus of the lateral lemniscus. Two major classes of neuron were identified: omnidirectional and directionally sensitive. Omnidirectional units exhibited azimuth functions that were either flat or that declined gradually at progressively ipsilateral azimuths. For the latter units, discharge rates at all points monotonically increased with stimulus intensity. There was no indication, for either type of omnidirectional unit, of significant binaural interaction. A good correlation was found between the summed proportions of excitatory-excitatory (EE) and monaural (EO) units observed in dichotic studies (46-55%) and the proportion of omnidirectional units in the present study (47%). A subgroup of directionally sensitive units (36% of the total) displayed azimuth functions for which the azimuthal position of the discharge border or peak firing azimuth remained essentially unaltered over a range of stimulus intensities. These azimuth-selective units are likely to have a role in the detection of the location of stimuli in the horizontal plane and appear to include units that would be considered excitatory-inhibitory (EI) or delay sensitive in dichotic studies. The azimuths over which directionally sensitive units showed their marked directional effects were influenced by the position of the contralateral pinna.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Response selectivity for multiple dimensions of frequency sweeps in the pallid bat inferior colliculus.

1. While hunting, the pallid bat uses passive sound localization at low frequencies to find terrestrial prey, and echolocation for general orientation. It must therefore process two different types of acoustic input at the same time. The pallid bat's echolocation pulse is a downward frequency-modulated (FM) sweep from 60 to 30 kHz. This study examined the response selectivity of single neurons in the pallid bat's central nucleus of the inferior colliculus (ICC) for FM sweeps, comparing the response properties of the high-frequency population, tuned to the biosonar pulse, with the low-frequency population, tuned below the pulse. The working hypothesis was that the high-frequency population would exhibit a response selectivity for downward FM sweeps that was not present in the low-frequency population. 2. Neurons were tested for their selectivity for FM sweep direction, duration, frequency range and bandwidth, and rate of frequency change. The extent to which they responded exclusively to tones, noise, and FM sweeps was also examined. Significant differences in the response properties of neurons in the two populations were found. In the low-frequency population, all neurons responded to tones, but only 50% responded to FM sweeps. Only 23% were selective for sweep direction. In the high-frequency population, all neurons responded to FM sweeps, but 31% did not respond to tones. Over one-half of this population was selective for sweep direction, and of those that were selective, all preferred the downward sweep direction of the biosonar pulse. A large percentage (31%) responded exclusively to downward sweeps, and not to tones or upward sweeps. None of the cells in either population responded to noise, or did so only at very high relative thresholds. 3. Both populations contained neurons that were selective for short stimulus durations that approximated the duration of the biosonar pulse, although the percentage was greater in the high-frequency population (58% vs. 20%). In the high-frequency population, 31% of the neurons tested for duration responded exclusively to both the sweep direction and duration of the biosonar pulse. 4. Downward FM-selective neurons, with one exception, were generally insensitive to the rate of frequency change of the FM sweep, as well as the frequency range and bandwidth of the sweep. They responded similarly to both the full 60- to 30-kHz sweep and to 5-kHz bandwidth portions of the full sweep.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

A specialization for speech perception.

The processes that underlie perception of consonants and vowels are specifically phonetic, distinct from those that localize sources and assign auditory qualities to the sound from each source. This specialization, or module, increases the rate of information flow, establishes the parity between sender and receiver that every communication system must have, and provides for the natural development of phonetic structures in the species and in the individual. The phonetic module has certain properties in common with modules that are "closed" (for example, sound localization or echo ranging in bats) and, like other members of this class, is so placed in the architecture of the auditory system as to preempt information that is relevant to its special function. Accordingly, this information is not available to such "open" modules as those for pitch, loudness, and timbre.

Animals

[The functional characteristics of ototopia during the monaural localization of a mobile sound object in space].

Ototopical function was studied in subjects with normal hearing by their mono- and binaural perception of the sound from a mobile source differently located in space. There was a relationship between ototopicometric parameters and acoustic system function. The discussion covers opportunities of ototopicometry in audiological evaluation of space hearing.

Adolescent

Neurological development of kittens.

The neurological development of the kitten was studied from birth to 120 days of age. Three motor features present at birth disappeared within the 1st 45 days of life. The labyrinthine head and body righting reactions were present at birth; the latter matured only by 25 days of age when the air righting reaction (mature by 35 days) started to appear. Limb placing reactions developed progressively with proprioceptive components being present at birth whereas tactile components evolved slowly from early contact lifting to forepaws contact placing (60 days) and narrow plank walking (75 days). Standing and walking were well developed by 45 days. Eye opening occurred at 9.5 days and several eyeblink reactions (including blink to light) were present at birth. Adequate binocular coordination was seen by 47 days. Vision progressed parallel to the clearing of the ocular media which were fairly transparent by 32 days. Visually guided paw placing and the visuopalpebral blink reflex matured later (by 37 and 59 days, respectively). The external auditory canal and pinna were fully developed by 12 and 31 days, respectively; spontaneous and tactile pinna movements were present at birth; orienting to animal and nonanimal sounds was well developed by 6.5 and 18 days, respectively; spatial sound localization was developed by 16 days and differential responding to animal sounds matured by 24.5 days. Somatic responses and olfaction were present at birth but matured further thereafter. Playful interactions between kittens started by 10--15 days and well developed play behavior was seen by 36--40 days. In brief, all neurological functions mature progressively during the 1st 3 postnatal months.

Animals

Plasticity in human directional hearing.

Interaural time difference (ITD), the main cue for localization of low-frequency sound in azimuth, is widely thought to be evaluated according to Jeffress' model. This theory proposes that each of an array of neurons detects coinciding input from both ears, conducted along axonal delay lines, with the azimuth angle corresponding to the activation of selected neurons. Thus, sound source localization is assumed to depend on axon conduction velocities, a relatively fixed parameter. Clinical experience suggests that directional hearing is adaptable. We investigated if sound localization in azimuth could adapt plastically to altered ITDs. We equipped binaural insert hearing aids with adjustable electronic delay lines. Subjects with normal hearing were required to wear these devices during all waking hours for several days. Localization of an invisible sound source was measured in an anechoic room before and at various intervals after introduction of a constant delay in one ear between 171 and 684 mus. Test sounds were high-pass, low-pass and broad-band noises. Introduction of a delay in one ear lead to an immediate displacement of the perceived sound location towards the opposite side. Within hours of exposure, the displacement was reduced, and further normalization of the perceived localization occurred over several days. After removal of the delays sound localization normalized rapidly. We conclude that ITD alterations can lead to plastic adaptation of directional hearing, which cannot rely exclusively on fixed axon conduction velocities. Our results suggest additional mechanisms for directional hearing on the basis ITD.

Acoustic Stimulation

[Audiological observations of a patient with auditory agnosia].

A case is reported in which a patient was become unable to identify all kinds of auditory material, including speech, despite only subnormal audiometric thresholds (i.e. "auditory agnosia"). The following audiological disorders were shown: some fragility in the perception of brief sound stimuli, difficulties to apprehending prolonged series of stimuli (rhythms), defective sound localization, an increase in the homolateral and in the contralateral effects of masking sounds. On the other hand, differential thresholds for frequency and for intensity, as well as fusion thresholds, were little affected, or unaffected. A complete dissociation appeared between the auditory evoked potentials and the audiometric thresholds; a year after the first examination, and the following years, the auditory potentials were largely reduced, or even have elapsed for one ear, while the audiometric thresholds seem to remain nearly the same.

Agnosia

Concerning the need for more sophisticated animal models in sensory behavioral toxicology.

It is necessary but not sufficient to develop laboratory animal models in sensory behavioral toxicology for screening toxic substances and for the analysis of sensory impairment at threshold levels of stimulation. It is important to develop more thorough and quantitative tests of impairment which in their greater complexity more accurately reflect the conditions and environmental demands of day-to-day life. Such greater complexity in stimulus conditions and behavior may also aid in monitoring not merely the state of the receptor organ but more central nervous processes which are the focus of assault by many known toxic substances. Techniques are described for studying such acoustic behaviors as intensity discrimination and frequency selectivity in guinea pig and monkey by use of operant conditioning procedures coupled with sensory testing (psychophysical) methods. Impaired auditory selectively and discrimination is shown to be correlated with histopathological changes in the inner ear. Slight modification of these procedures in animals may be used to investigate acoustically more intricate behaviors such as sound localization and the perception of frequency modulated acoustic signals as elements of speech and communication sounds.

Acoustic Stimulation

Hearing in domestic pigs (Sus scrofa) and goats (Capra hircus).

Behavioral audiograms were determined for three pigs and two goats. The hearing of the pigs ranged from 42 Hz to 40.5 kHz with a region of best sensitivity from 250 Hz to 16 kHz. Hearing in goats ranged from 78 Hz to 37 kHz with a well-defined point of best sensitivity at 2 kHz. Because these animals are unable to localize high-frequency tones, it seems unlikely that selective pressure to use the interaural spectral-difference cue for sound localization is behind their high-frequency hearing. Instead, we suggest that these and other hoofed mammals evolved high-frequency hearing in order to use monaural locus cues which prevent front/back locus reversals.

Acoustic Stimulation

Psychoacoustical contribution of each lateral lemniscus.

Although each lateral lemniscus is required for sound localization in its contralateral hemifield, no auditory function is yet known for the neural activity evoked in the lemniscus ipsilateral to a sound source. In an attempt to assess the role played by the ipsilateral lemniscus, monaural cats were tested on an array of psychoacoustical tasks before and after surgical section of one or the other lateral lemniscus. The results show that the lemniscus contralateral to the remaining intact ear is either necessary or sufficient for 24 of the 26 tests administered. However, the lemniscus ipsilateral to the intact ear is both necessary and sufficient (or alternatively, the contralateral lemniscus makes no obvious contribution) to normal thresholds in two of the tasks: detection of low-frequency tones (< 4 kHz) and detection of low-frequency AM modulation. Because of their projections to the ipsilateral inferior colliculus via the ipsilateral lemniscus, the anatomical substrate of these two unusual tasks is probably the fibers from the MSO and possibly, the LSO, ipsilateral to the intact ear.

Acoustic Stimulation

Classification of response patterns in cochlear nucleus of barn owl: correlation with functional response properties.

Response patterns of neurons in the cochlear nuclei of the barn owl (Tyto alba) were studied by obtaining poststimulus time histograms (PSTHs) and interspike interval histograms for the response to short tone bursts at the neuron's characteristic frequency. The observed response patterns can be classified according to the scheme developed for neurons of the mammalian cochlear nuclear complex (22). Neurons of the magnocellular cochlear nucleus (n. magnocellularis), which respond in a phase-locked manner to sinusoidal signals and do not show large increases in spike discharge rate with changes in stimulus intensity (26), have "primarylike" (PSTH) discharge patterns and broad interspike interval histograms. This indicates that magnocellular neurons have irregular firing patterns, with the timing of individual spikes being dependent on the phase of the stimulus waveform. Neurons of the angular cochlear nucleus (n. angularis), which show little or no phase-locking and large increases in spike rate with increasing intensity (26), had almost exclusively "transient chopper" discharge patterns. The interspike interval histograms of these angular units are sharp, indicating that their discharge is very regular. At the onset of the response where the chopper pattern is observed, both discharge regularity and rate-intensity sensitivity are at their maximum levels. Several "onset" units were isolated in the angular cochlear nucleus, but no "pauser" or "buildup" units were seen. Also, all of the units in the angular nucleus had monotonic rate-intensity functions. Thus no neural response patterns typical of mammalian dorsal cochlear nucleus units were observed. The relationship of response pattern type to neural function is discussed in relation to the acoustic cues used by the owl for two-dimensional sound localization. The primarylike, phase-locked discharge of magnocellular units is undoubtedly involved in the analysis of interaural differences in stimulus phase, which the owl uses for horizontal localization. There is strong evidence suggesting that the angular nucleus is involved in processing stimulus intensity information, which is important for determining sound elevation (due to asymmetries in vertical directionality of the owl's external ears). The predominant chopper patterns seen in the angular nucleus suggest that in the owl, this response type is correlated with stimulus intensity processing. Similarities in both anatomy and physiology suggest that the magnocellular nucleus is analogous to the spherical cell or bushy cell population of the anterior division of the mammalian anteroventral cochlear nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Frequency dependence of directional amplification at the cat's pinna.

We examined in detail the effects of changing stimulus frequency upon the inclination of the acoustical axis of the pinna and upon the solid angle (area) subtended by isoamplification contours. We measured the relative sound pressure level difference between points on a 1 m radius, coordinate sphere using the cochlear microphonic as an indicator of tympanic sound pressure. The inclination of the acoustical axis for a given frequency was found to vary with the posture of the pinna, and with the pinna in a drooped position (following midline incision) there was a frequency spreading of axial positions such that high frequency axes were inclined progressively more laterally. However, with the pinna in an upright posture the axes for all frequencies tested were relatively tightly clustered. Alternative models for sound localization can be formulated to suit either situation, but it seems likely that the cat can use the frequency spreading effect of its pinna sound transformation as a cue to location. The pinna becomes more directional at higher frequencies, and this is clearly shown when the solid angle of isoamplification contours is plotted against frequency. The inverse relationship formed was shown to be closely matched by a model based upon diffraction by the outer dimension of the pinna.

Acoustics

Long-latency auditory evoked potentials in humans and the localization of a sound image.

In the article, we discuss data from an investigation concerning how boundary conditions for the creation of sound-image movement are reflected long-latency auditory evoked potentials and discuss how and important associated with the human localizing function (resistance to interference during the local localization of both a stationary and a moving sound image) appears in long-latency auditory evoked potentials. We establish that a change in the parameters of a signal creating a sensation of sound-image movement results in an exhaltation of t he amplitudes of the N1 and P2 components. The effect of binaural freedom from masking is reflected in these same components of long-latency auditory evoked potentials during movement of spatially shifting signals.

Acoustic Stimulation

Projections of the cochlear nuclei and nucleus laminaris to the inferior colliculus of the barn owl.

The barn owl determines the directions from which sounds emanate by computing the interaural differences in the timing and intensity of sounds. These cues for sound localization are processed in independent channels originating at nucleus magnocellularis (NM) and nucleus angularis (NA), the cochlear nuclei. The cells of NM are specialized for encoding the phase of sounds in the ipsilateral ear. The cells of NA are specialized for encoding the intensity of sounds in the ipsilateral ear. NM projects solely, bilaterally, and tonotopically to nucleus laminaris (NL). NL and NA project to largely nonoverlapping zones in the central nucleus of the inferior colliculus (ICc), thus forming hodological subdivisions in which time and intensity information may be processed. The terminal field of NL occupies a discrete zone in the rostromedial portion of the contralateral ICc, which we have termed the "core" of ICc. The terminal field of NA surrounds the core of ICc and thus forms a "shell" around it. The projection from NL to the core conserves tonotopy. Low-frequency regions of NL project to the dorsal portions of the core whereas higher-frequency regions project to more ventral portions. This innervation pattern is consistent with earlier physiological studies of tonotopy. Physiological studies have also suggested that NL and the core of ICs contain a representation of the location of a sound source along the horizontal axis. Our data suggest that the projection from NL to the core preserves spatiotopy. Thus, the dorsal portion of NL on the left, which contains a representation of eccentric loci in the right hemifield, innervates the area of the right ICc core that represents eccentric right loci. The more ventral portion of the left NL, which represents loci close to the vertical meridian, innervates the more rostral portions of the right core, which also represents loci near the vertical meridian.

Afferent Pathways

Comparison of normal and impaired hearing. I. Loudness, localization.

Impaired hearing is characterized by high thresholds and reduced loudness. Loudness, however, may quickly recover as it increases rapidly from an elevated threshold. This rapid growth, known as loudness recruitment, is a sign of cochlear impairment and is generally not seen in conductive or retrocochlear impairment. Loudness recruitment means that the hard-of-hearing person detects small changes in intensity near his elevated threshold but he probably does no better than a normal listener at the same SPLs. Recruitment is often accompanied by reduced loudness summation, which means that the loudness of a band of noise does not increase as much with increasing bandwidth as in normal hearing. This reduced summation of loudness is probably why the cochlearly impaired ear has nearly the same threshold for the acoustic reflex to pure tones as to wide-band noise, whereas the normal ear has a much lower threshold to wide-band noise. Corresponding differences between normal and impaired hearing are not found in auditory localization. Rather, the evidence suggests that persons with residual hearing learn to localize sounds reasonably well. Even the inability of many hearing impaired persons to understand a speaker in a noisy environment may result more from a failure of frequency analysis rather than of localization.

Auditory Threshold

Sound delay lines in the nucleus laminaris of the chicken.

Delays of neurophonic potentials (NP) induced by monaural sound stimuli were measured across the three dimensions in the nucleus laminaris (NL) of the anesthetized chicken. Peak latencies and delays in cross-correlograms changed with recording distance. An orderly delay line was observed across the NL thickness, that is, along dendritic trees of individual fusiform cells (FC), where phase lags increased dorso-ventrally during ipsi- and in the opposite direction during contralateral stimuli. Delays along isofrequency FC arrays were variable, with delay ranges being smaller for ipsilateral than for contralateral sound stimuli. Net delays for contralateral sounds were directed medio-laterally and differences between ipsi- and contralateral delays covered, roughly, intercochlear time differences (ITD). The observed delays are thought to contribute to sound localization and frequency analysis.

Animals