Organization of inhibitory frequency receptive fields in cat primary auditory cortex

Based on properties of excitatory frequency (spectral) receptive fields (esRFs), previous studies have indicated that cat primary auditory cortex (A1) is composed of functionally distinct dorsal and ventral subdivisions. Dorsal A1 (A1d) has been suggested to be involved in analyzing complex spectral patterns, whereas ventral A1 (A1v) appears better suited for analyzing narrowband sounds. However, these studies were based on single-tone stimuli and did not consider how neuronal responses to tones are modulated when the tones are part of a more complex acoustic environment. In the visual and peripheral auditory systems, stimulus components outside of the esRF can exert strong modulatory effects on responses. We investigated the organization of inhibitory frequency regions outside of the pure-tone esRF in single neurons in cat A1. We found a high incidence of inhibitory response areas (in 95% of sampled neurons) and a wide variety in the structure of inhibitory bands ranging from a single band to more than four distinct inhibitory regions. Unlike the auditory nerve where most fibers possess two surrounding "lateral" suppression bands, only 38% of A1 cells had this simple structure. The word lateral is defined in this sense to be inhibition or suppression that extends beyond the low- and high-frequency borders of the esRF. Regional differences in the distribution of inhibitory RF structure across A1 were evident. In A1d, only 16% of the cells had simple two-banded lateral RF organization, whereas 50% of A1v cells had this organization. This nonhomogeneous topographic distribution of inhibitory properties is consistent with the hypothesis that A1 is composed of at least two functionally distinct subdivisions that may be part of different auditory cortical processing streams.     

Effects of auditory cortical lesions on pure-tone sound localization by the albino rat

Two-choice and three-choice tests were used to evaluate the effects of bilateral auditory cortical lesions on pure-tone sound localization by the albino rat. Both tests required that animals approach a distant sound source to obtain water reinforcement. Stimuli were single noise and tone bursts, 65 ms in duration including 20-ms rise and fall times. Tone frequencies were 2, 4, 8, 16, and 32 kHz adjusted to 40 dB (SPL) above the rat's absolute threshold. Five animals were tested in the two-choice situation following bilateral ablation of auditory cortex. Some reduction in performance was observed relative to normals, but impairments were not severe. Similar results were obtained for 2 brain-damaged animals tested in the three-choice situation. Thus, the ability to localize sounds in space remained intact after complete destruction of auditory cortex, and there was no indication of a frequency-dependent deficit.     

Enlargement of neuronal size in rat auditory cortex after prolonged sound exposure

Prolonged sound exposure produces functional changes in the auditory neurons. It remains unclear whether such changes are detectable with morphometric measures like cell size. Here, after exposing juvenile rats (starting on week-4) to a monotone for 7 days, we measured the size of their cortical neurons. Neuronal profiles (nuclei and perikarya) in deep layers of the primary auditory cortex were digitized and measured on photomicrographs taken from 7 μm-thick histological sections stained with toluidine blue. To facilitate digitizing cell profiles, we used an image-analysis software that contains a confocal-like image-merging function to sharpen the edges. After sound exposure, both nuclei and perikarya expanded by about 1/3 in volume compared with controls (p < 0.0001, Student's t-test). Such changes were not found in the visual cortex. Results showed that prolonged sound exposure increased the size of auditory neurons. Such activity-driven cell enlargement can be used as a simple measure to find other plastic changes in the brain.     

Sensitivity to simulated directional sound motion in the rat primary auditory cortex.

Sensitivity to simulated directional sound motion in the rat primary auditory cortex. This paper examines neuron responses in rat primary auditory cortex (AI) during sound stimulation of the two ears designed to simulate sound motion in the horizontal plane. The simulated sound motion was synthesized from mathematical equations that generated dynamic changes in interaural phase, intensity, and Doppler shifts at the two ears. The simulated sounds were based on moving sources in the right frontal horizontal quadrant. Stimuli consisted of three circumferential segments between 0 and 30 degrees, 30 and 60 degrees, and 60 and 90 degrees and four radial segments at 0, 30, 60, and 90 degrees. The constant velocity portion of each segment was 0.84 m long. The circumferential segments and center of the radial segments were calculated to simulate a distance of 2 m from the head. Each segment had two trajectories that simulated motion in both directions, and each trajectory was presented at two velocities. Young adult rats were anesthetized, the left primary auditory cortex was exposed, and microelectrode recordings were obtained from sound responsive cells in AI. All testing took place at a tonal frequency that most closely approximated the best frequency of the unit at a level 20 dB above the tuning curve threshold. The results were presented on polar plots that emphasized the two directions of simulated motion for each segment rather than the location of sound in space. The trajectory exhibiting a "maximum motion response" could be identified from these plots. "Neuron discharge profiles" within these trajectories were used to demonstrate neuron activity for the two motion directions. Cells were identified that clearly responded to simulated uni- or multidirectional sound motion (39%), that were sensitive to sound location only (19%), or that were sound driven but insensitive to our location or sound motion stimuli (42%). The results demonstrated the capacity of neurons in rat auditory cortex to selectively process dynamic stimulus conditions representing simulated motion on the horizontal plane. Our data further show that some cells were responsive to location along the horizontal plane but not sensitive to motion. Cells sensitive to motion, however, also responded best to the moving sound at a particular location within the trajectory. It would seem that the mechanisms underlying sensitivity to sound location as well as direction of motion converge on the same cell.     

Contextual modulation of frequency tuning of neurons in the rat auditory cortex

In a natural acoustic environment, sound stimuli often occur in a contextual acoustic stream. The aim of the present study was to determine how the frequency tuning of auditory cortical neurons is affected by an acoustic context. A forward masking paradigm was used to determine the frequency receptive fields of rat auditory cortex neurons under quiet and sequential sound conditions. The frequency receptive fields of a cortical neuron were modulated dynamically by a preceding sound stimulus. At a fixed interstimulus interval (ISI), if the preceding sound level was constant, the receptive fields of most neurons were modulated to the greatest extent when the preceding sound frequency was at or near the characteristic frequency of the neuron; if the preceding sound frequency was constant, the modulation was increased with increasing sound stimulus level. When both the frequency and the level of the preceding sound were fixed, the modulation decreased with increasing interstimulus interval. The results indicate that the frequency tuning of auditory cortical neurons is plastic and dynamically modulated in a reverberant acoustical environment, and the degree of modulation depends on both the frequency tuning of the neuron and the contextual acoustical stream.     

Anesthesia changes frequency tuning of neurons in the rat primary auditory cortex

The vast majority of investigations on central auditory processing so far were conducted under the influence of an anesthetic agent. It remains unclear, however, to what extend even basic response properties of central auditory neurons are influenced by this experimental manipulation. We used a combination of chronic recording in unrestrained animals, computer-controlled randomized acoustic stimulation, and statistical evaluation of responses to directly compare the response characteristics of single neurons in the awake and anesthetized state. Thereby we were able to quantify the effects of pentobarbital/chloral hydrate anesthesia (Equithesin) on rat auditory cortical neurons. During Equithesin anesthesia, only a portion of central neurons were active and some of their basic response properties were changed. Only 29% of the neurons still had a frequency response area. Their tuning sharpness was increased under anesthesia. Most changes are consistent with an enhancement of inhibitory influences during Equithesin anesthesia. Thus when describing response properties of central auditory neurons, the animal's anesthetic state has to be taken into account.     

Tuning to sound frequency in auditory field potentials

Neurons in auditory cortex are selective for the frequency content of acoustical stimuli. Classically, this response selectivity is studied at the single-neuron level. However, current research often employs functional imaging techniques to investigate the organization of auditory cortex. The signals underlying the imaging data arise from neural mass action and reflect the properties of populations of neurons. For example, the signal used for functional magnetic resonance imaging (fMRI-BOLD) was shown to correlate with the oscillatory activity quantified by local field potentials (LFPs). This raises the questions of how the frequency selectivity in neuronal population signals compares with the tuning of spiking responses. To address this, we quantified tuning properties of auditory-evoked potentials (AEP), different frequency bands of the LFP, analog multi-unit (AMUA), and spike-sorted single- and multiunit activity in auditory cortex. The AMUA showed a close correspondence in frequency tuning to the spike-sorted activity. In contrast, for the LFP, we found a clear dissociation of high- and low-frequency bands: there was a gradual increase of tuning-curve similarity, tuning specificity, and information about the stimulus with increasing LFP frequency. Although properties of the high-frequency LFP matched those of spiking activity, the lower-frequency bands differed considerably as did the AEP. These results demonstrate that electrophysiological population responses exhibit varying degrees of frequency tuning and suggest that those functional imaging methods that are related to high-frequency oscillatory activity should well reflect the neuronal processing of sound frequency.     

Role of auditory cortex in sound localization in the midsagittal plane

Although the auditory cortex is known to be essential for normal sound localization in the horizontal plane, its contribution to vertical localization has not so far been examined. In this study, we measured the acuity with which ferrets could discriminate between two speakers in the midsagittal plane before and after silencing activity bilaterally in the primary auditory cortex (A1). This was achieved either by subdural placement of Elvax implants containing the GABA A receptor agonist muscimol or by making aspiration lesions after determining the approximate location of A1 electrophysiologically. Psychometric functions and minimum audible angles were measured in the upper hemifield for 500-, 200-, and 40-ms noise bursts. Muscimol-Elvax inactivation of A1 produced a small but significant deficit in the animals' ability to localize brief (40-ms) sounds, which was reversed after removal of the Elvax implants. A similar deficit in vertical localization was observed after bilateral aspiration lesions of A1, whereas performance at longer sound durations was unaffected. Another group of ferrets received larger lesions, encompassing both primary and nonprimary auditory cortical areas, and showed a greater deficit with performance being impaired for long- and short-duration (500- and 40-ms, respectively) stimuli. These data suggest that the integrity of the auditory cortex is required to successfully utilize spectral localization cues, which are thought to provide the basis for vertical localization, and that multiple cortical fields, including A1, contribute to this task.     

Processing of sound sequences in macaque auditory cortex: response enhancement.

It is well established that the tone-evoked response of neurons in auditory cortex can be attenuated if another tone is presented several hundred milliseconds before. The present study explores in detail a complementary phenomenon in which the tone-evoked response is enhanced by a preceding tone. Action potentials from multiunit groups and single units were recorded from primary and caudomedial auditory cortical fields in lightly anesthetized macaque monkeys. Stimuli were two suprathreshold tones of 100-ms duration, presented in succession. The frequency of the first tone and the stimulus onset asynchrony (SOA) between the two tones were varied systematically, whereas the second tone was fixed. Compared with presenting the second tone in isolation, the response to the second tone was enhanced significantly when it was preceded by the first tone. This was observed in 87 of 130 multiunit groups and in 29 of 69 single units with no obvious difference between different auditory fields. Response enhancement occurred for a wide range of SOA (110-329 ms) and for a wide range of frequencies of the first tone. Most of the first tones that enhanced the response to the second tone evoked responses themselves. The stimulus, which on average produced maximal enhancement, was a pair with a SOA of 120 ms and with a frequency separation of about one octave. The frequency/SOA combinations that induced response enhancement were mostly different from the ones that induced response attenuation. Results suggest that response enhancement, in addition to response attenuation, provides a basic neural mechanism involved in the cortical processing of the temporal structure of sounds.     

Topographic organization of the auditory thalamocortical system in the albino rat

Summary The organization of the auditory thalamocortical connections was studied in rats. Retrograde transport of horseradish peroxidase conjugated to wheat germ agglutinin following injections into parietal, occipital and temporal cortex was used. The medial geniculate body, the suprageniculate, the lateral part of the nucleus posterior thalami, the posterior part of the nucleus lateralis thalami, and the nucleus ventroposterior project to the investigated part of the neocortex. Corresponding to different patterns of labeling, five areas of auditory neocortex were distinguished: 1. The rostral area is innervated by neurons of the nucleus ventroposterior, the lateral part of the nucleus posterior thalami, and the medial division of the medial geniculate body. 2. The dorsal area is innervated by neurons of the suprageniculate, the posterior part of the nucleus lateralis thalami and the rostral region of the dorsal division of the medial geniculate body. 3. The caudal area is innervated by neurons of the posterior part of the nucleus lateralis thalami, the suprageniculate, the medial division, the caudal region of the dorsal division and the ventrolateral nucleus of the medial geniculate body. 4. The ventral area is innervated by neurons of the suprageniculate, the medial division, the caudal region of the dorsal division, and the ventrolateral nucleus of the medial geniculate body. 5. The core area of the temporal cortex is exclusively connected to the caudal region of the medial division and the ventral division of the medial geniculate body.The findings of the present study indicate topographic organizations of the ventral division of the medial geniculate body and of the corea area. Four segments (a-d) of the ventral division each show a different set of topographic axes. They correspond to sets of topographic axes in the core area of the auditory cortex. These topographies characterize the segments which are each exclusively connected to one of the four fields of the core area.Abbreviations AC Auditory Cortex - c Caudal - d Dorsal - FR Fissura rhinalis, Rhinal Fissure - l Lateral - LTP Nucleus lateralis thalami, pars posterior - m Medial - MGB Medial geniculate body - MGBd Medial geniculate body, dorsal division - MGBm Medial geniculate body, medial division - MGBmc Medial geniculate body, caudal third of MGBm - MGBv Medial geniculate body, ventral division - MGBvl Medial geniculate body, ventrolateral nucleus - NPT Nucleus posterior thalami, pars lateralis - r Rostral - SG Suprageniculatum - VP Nucleus ventroposterior     

Role of mammalian auditory cortex in the perception of elementary sound properties

Studies in several mammalian species have demonstrated that bilateral ablations of the auditory cortex have little effect on simple sound intensity and frequency-based behaviors. In the rat, for example, early experiments have shown that auditory ablations result in virtually no effect on the rat's ability to either detect tones or discriminate frequencies. Such lesion experiments, however, typically examine an animal's performance some time after recovery from ablation surgery. As such, they demonstrate that the cortex is not essential for simple auditory behaviors in the long run. Our study further explores the role of cortex in basic auditory perception by examining whether the cortex is normally involved in these behaviors. In these experiments we reversibly inactivated the rat primary auditory cortex (AI) using the GABA agonist muscimol, while the animals performed a simple auditory task. At the same time we monitored the rat's auditory activity by recording auditory evoked potentials (AEP) from the cortical surface. In contrast to lesion studies, the rapid time course of these experimental conditions preclude reorganization of the auditory system that might otherwise compensate for the loss of cortical processing. Soon after bilateral muscimol application to their AI region, our rats exhibited an acute and profound inability to detect tones. After a few hours this state was followed by a gradual recovery of normal hearing, first of tone detection and, much later, of the ability to discriminate frequencies. Surface muscimol application, at the same time, drastically altered the normal rat AEP. Some of the normal AEP components vanished nearly instantaneously to unveil an underlying waveform, whose size was related to the severity of accompanying behavioral deficits. These results strongly suggest that the cortex is directly involved in basic acoustic processing. Along with observations from accompanying multiunit experiments that related the AEP to AI neuronal activity, our results suggest that a critical amount of activity in the auditory cortex is necessary for normal hearing. It is likely that the involvement of the cortex in simple auditory perceptions has hitherto not been clearly understood because of underlying recovery processes that, in the long-term, safeguard fundamental auditory abilities after cortical injury.     

Activation of the primary and association auditory cortex by the transition of sound intensity: a new method for functional examination of the auditory cortex in humans

During functional MRI image acquisition, the scanning equipment generates substantial auditory noise, the effects of which are usually ignored. To investigate the neural activity in response to the transition of noise, we measured cerebral responses to short silent periods (1 and 5 s) during which the slice readout gradients were switched off. In all 15 normal volunteers, the 1 s silence bilaterally activated the primary and association auditory cortex. Subtraction of the response to the 1 s silent period from that to the 5 s silent period revealed the activation related to the onset (transition of sound from OFF to ON) event, indicating that the 1 s response is offset (transition of sound from ON to OFF) related. The complex response of the auditory cortex to the transition of the noise should be considered in designing functional MRI with auditory tasks.     

Fine frequency tuning in monkey auditory cortex and thalamus

The frequency resolution of neurons throughout the ascending auditory pathway is important for understanding how sounds are processed. In many animal studies, the frequency tuning widths are about 1/5th octave wide in auditory nerve fibers and much wider in auditory cortex neurons. Psychophysical studies show that humans are capable of discriminating far finer frequency differences. A recent study suggested that this is perhaps attributable to fine frequency tuning of neurons in human auditory cortex (Bitterman Y, Mukamel R, Malach R, Fried I, Nelken I. Nature 451: 197-201, 2008). We investigated whether such fine frequency tuning was restricted to human auditory cortex by examining the frequency tuning width in the awake common marmoset monkey. We show that 27% of neurons in the primary auditory cortex exhibit frequency tuning that is finer than the typical frequency tuning of the auditory nerve and substantially finer than previously reported cortical data obtained from anesthetized animals. Fine frequency tuning is also present in 76% of neurons of the auditory thalamus in awake marmosets. Frequency tuning was narrower during the sustained response compared to the onset response in auditory cortex neurons but not in thalamic neurons, suggesting that thalamocortical or intracortical dynamics shape time-dependent frequency tuning in cortex. These findings challenge the notion that the fine frequency tuning of auditory cortex is unique to human auditory cortex and that it is a de novo cortical property, suggesting that the broader tuning observed in previous animal studies may arise from the use of anesthesia during physiological recordings or from species differences.     

Effect of bilateral auditory cortex lesions on sound localization in Japanese macaques

1. The ability of four Japanese macaques (Macaca fuscata) to localize sound was determined after bilateral ablation of auditory cortex. The animals were given two tests: a "midline" test in which they had to discriminate noise bursts presented from a loudspeaker located to the left from identical noise bursts presented from a loudspeaker located to the right of midline, and a "hemifield" test in which both loudspeakers were located in their right hemifield. 2. Both of the tests were administered by the use of two different behavioral tasks: a conditioned-avoidance task in which the animals were trained to make or break contact with a water spout to indicate the location of a sound source, and a two-choice task that required the animals to walk to the source of the sound. 3. The results of both the conditioned-avoidance and the two-choice tasks demonstrated that the animals were able to perform the midline discrimination although their localization acuity was reduced. However, the animals had great difficulty in learning to walk to the source of a sound in spite of the fact that they had received previous sound-localization training in the conditioned-avoidance task. This difficulty suggested that the monkeys no longer associated the sound with a location in space. 4. The results of both the conditioned-avoidance and the two-choice tasks demonstrated that the animals were unable to discriminate the locus of a sound source when both loudspeakers were located in the same hemifield. 5. Bilateral ablation of auditory cortex results in both sensory and perceptual deficits. The presence of sensory deficits is indicated by the decreased acuity in the left-right discrimination and the inability to discriminate between two loudspeakers located in the same hemifield. The deficit in the perception of the locus of sound is indicated by the difficulty in learning to approach the source of a sound, an ability which normal monkeys exhibit without training. 6. There appear to be species' differences in the effect of auditory cortex lesions on sound localization. Although cortical lesions result in a sound-localization deficit in several species of primates and carnivores, they have little or no effect on rats.