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Gamma-aminobutyric acid circuits shape response properties of auditory cortex neurons.

Neurons containing gamma aminobutyric acid (GABA) are widely distributed throughout the primary auditory cortex (AI). We investigated the effects of endogenous GABA by comparing response properties of 110 neurons in chinchilla AI before and after iontophoresis of bicuculline, a GABA(A) receptor antagonist, and/or CGP35348, a GABA(B) receptor antagonist. GABA(A) receptor blockade significantly increased spontaneous and driven discharge rates, dramatically decreased the thresholds of many neurons, and constricted the range of thresholds across the neural population. Some neurons with 'non-onset' temporal discharge patterns developed an onset pattern that was followed by a long pause. Interestingly, the excitatory response area typically expanded on both sides of the characteristic frequency; this expansion exceeded one octave in a third of the sample. Although GABA(B) receptor blockade had little effect alone, the combination of CGP35348 and bicuculline produced greater increases in driven rate and expansion of the frequency response area than GABA(A) receptor blockade alone, suggesting a modulatory role of local GABA(B) receptors. The results suggest that local GABA inhibition contributes significantly to intensity and frequency coding by controlling the range of intensities over which cortical neurons operate and the range of frequencies to which they respond. The inhibitory circuits that generate nonmonotonic rate-level functions are separate from those that influence other response properties of AI neurons.

Acoustic Stimulation↗

Tonotopic organization of human auditory cortex revealed by multi-channel SQUID system.

A 14-channel SQUID (superconducting quantum interference device) system has been used to record the magnetic signal from the human brain in response to an auditory stimuli (750, 1,000, 1,250 and 1,500 Hz, 70, 76 and 82 dB SPL, 500 ms duration). Three individuals with normal hearing were studied. The locations of magnetic response at the latency of 70 ms (P70), 100 ms (N100) and 160 ms (P160) from the onset of the auditory stimulus were identified. The location for N100 response corresponded to the primary auditory cortex (area 41), where a clear tonotopic organization was demonstrated. The amplitopic organization was less evident. These results suggest a flow of auditory signals in the temporal lobe and tonotopic organization in the auditory cortex.

Auditory Cortex↗

Some neural mechanisms in the cat's auditory cortex underlying sensitivity to combined tone and wide-spectrum noise stimuli.

In the auditory cortex of nitrous oxide-anesthetized, muscle-relaxed cats, single neurons were studied for their responsiveness to pure tones that were mixed acoustically with simultaneously gated wide-spectrum noise bursts presented using a calibrated sealed stimulating system. The intensities of both the tone and the noise were systematically varied, with a view to ascertaining the sensitivity of cortical cells to a characteristic frequency tone delivered in the presence of a noise mask. Neurons for which wide-spectrum noise provided a net excitatory influence typically displayed a 'strong-signal capture' effect; that is, the cell's responses were dominated by whichever of the two elements of the combined stimulus was the more effective when tested separately. These cells generally had monotonic tone rate intensity functions. Most of the cells that were suppressed by the noise displayed nonmonotonic pure tone rate intensity functions. When nonmonotonic cells were studied with the combined stimulus, the noise was found to produce an intensity-dependent suppression of their tone-evoked responses that could not be overcome by elevating the tone intensity. In contrast, for the minority of monotonic neurons whose tone-evoked responses were suppressed by noise, that suppression could be overcome by raising the tone intensity. None of the cells in the sample responded in a sustained fashion to continuous noise. In each of 11 cases examined, the effect of a continuous noise mask was to elevate tone thresholds and to prolong latent periods for tones; the magnitude of both of these effects depended on the intensity of the continuous noise mask.

Animals↗

NADPH-diaphorase-positive neurons in the auditory cortex of young and old rats.

Age-related changes in NADPH-diaphorase (NADPH-d)-positive neurons were examined in the auditory cortex of young (3 months old) and very old (36 months old) rats (strain Long Evans). In very old rats a significant reduction was found in the thickness of the auditory cortex, to 54% of that in young animals, as well as changes in the shape and configuration of nerve cell bodies and dendrites. Quantitative analysis demonstrated an age-related increase in the number of dendritic segments and dendritic branching points. The length of dendrites in NADPH-d-positive neurons and their density increased in very old rats. The total number of NADPH-d-positive neurons within the Te 1 and Te 3 fields was 13% lower in the old rats than in the young.

Aging↗

Inner hair cell loss leads to enhanced response amplitudes in auditory cortex of unanesthetized chinchillas: evidence for increased system gain.

Carboplatin preferentially destroys inner hair cells (IHCs) in the chinchilla inner ear, while retaining a near-normal outer hair cell (OHC) population. The present study investigated the functional consequences of IHC loss on the compound action potential (CAP), inferior colliculus potential (ICP) and auditory cortex potential (ACP) recorded from chronically implanted electrodes. IHC loss led to a reduction in CAP amplitude that was roughly proportional to IHC loss. The ICP amplitude was typically reduced by IHC loss, but the magnitude of this reduction was generally less than that observed for the CAP. In contrast to the CAP and ICP, ACP amplitudes were generally not reduced following IHC loss. In some animals, the ACP amplitude remained at pre-carboplatin values despite substantial IHC loss. However, in other animals, IHC loss led to an increase ('enhancement') of ACP amplitude. ACP enhancement was greatest at 1-2 weeks post-carboplatin, returning towards baseline amplitudes at 5 weeks post-carboplatin. In other animals, the ACP remained enhanced up to 5 weeks post-carboplatin. We interpret the transient and sustained enhancement of ACP amplitude following partial IHC loss as evidence of functional reorganization occurring at or below the level of the auditory cortex. These results suggest that the gain of the central auditory pathway increases following IHC loss to compensate for the reduced input from the cochlea.

Action Potentials↗

Bilateral transitory projection to visual areas from auditory cortex in kittens.

A transitory projection from primary and secondary auditory areas to the contralateral and ipsilateral areas 17 and 18 exists in newborn kittens. Distinct neuronal populations project to ipsilateral areas 17-18, contralateral areas 17-18 and contralateral auditory cortex; they are at different depth in layers II, III, and IV. By postnatal day 38 the auditory to visual projections have been lost, apparently by elimination of axons rather than by neuronal death. While it was previously reported that the elimination of transitory axons is responsible for focusing the origin of callosal connections to restricted portions of sensory areas it now appears that similar events play a more general role in the organization of cortico-cortical networks. Indeed, the elimination of juvenile projections is largely responsible for determining which areas will be connected in the adult.

Animals↗

Projections from auditory cortex to the cochlear nucleus in rats: synapses on granule cell dendrites.

Previous work has demonstrated that layer V pyramidal cells of primary auditory cortex project directly to the cochlear nucleus. The postsynaptic targets of these centrifugal projections, however, are not known. For the present study, biotinylated dextran amine, an anterograde tracer, was injected into the auditory cortex of rats, and labeled terminals were examined with light and electron microscopy. Labeled corticobulbar axons and terminals in the cochlear nucleus are found almost exclusively in the granule cell domain, and the terminals appear as boutons (1-2 microns in diameter) or as small mossy fiber endings (2-5 microns in diameter). These cortical endings contain round synaptic vesicles and form asymmetric synapses on hairy dendritic profiles, from which thin (0.1 micron in diameter), nonsynaptic "hairs" protrude deep into the labeled endings. These postsynaptic dendrites, which are typical of granule cells, surround and receive synapses from large, unlabeled mossy fiber endings containing round synaptic vesicles and are also postsynaptic to unlabeled axon terminals containing pleomorphic synaptic vesicles. No labeled fibers were observed synapsing on profiles that did not fit the characteristics of granule cell dendrites. We describe a circuit in the auditory system by which ascending information in the cochlear nucleus can be modified directly by descending cortical influences.

Animals↗

Increased right auditory cortex activity in absolute pitch possessors.

We recorded the auditory-evoked magnetic fields from children and adults with absolute pitch during the following tasks: (1) hearing 1000 Hz pure tones inattentively, (2) hearing eight random tones inattentively and (3) listening to eight random tones and identifying each tone. In children with absolute pitch, there was no significant positive correlation between the appearance rate of N100m and the kinds of tasks. In adults with absolute pitch, only the right N100m dipole moments increased significantly in tasks (1) and (2). The present results suggest that the circuit for labeling in the right auditory cortex may lose a function from childhood to adulthood, which reveals neuroplasticity in the development of absolute pitch ability.

Acoustic Stimulation↗

Neural interaction in cat primary auditory cortex II. Effects of sound stimulation.

1. The effect of auditory stimulation with click trains, noise bursts, amplitude-modulated noise bursts, and amplitude-modulated tone bursts on the correlation of firing of 1,290 neuron pairs recorded on one or two electrodes in primary auditory cortex of the cat was investigated. A distinction was made between neural synchrony (the correlation under stimulus conditions) and neural correlation (the correlation under spontaneous or under stimulus conditions after correction for stimulus-related correlations). For neural correlation 63% of the single-electrode pairs showed a unilateral excitation component, often combined with a common-input peak, and only 11% of the dual electrode pairs showed this unilateral excitation. 2. Under poststimulus conditions the incidence of correlograms with clear peaks was high for single-electrode pairs (80-90% range) and somewhat lower for dual-electrode pairs (50-60% range). The strength of the neural correlation for poststimulus conditions, from 0.5 to 2 s after a 1-s stimulus, was comparable with that obtained for 15-min continuous silence, suggesting that aftereffects of stimulation had largely disappeared after 0.5 s. A stationary analysis of the correlation coefficient corroborated this. 3. Two stimulus-correction procedures, one based on the shift predictor and the other based on the joint peristimulus-time histogram (JPSTH) were compared. The mean value of the neural correlation under stimulus conditions obtained after applying the poststimulus time (PST) predictor was on average 20% larger than the mean value obtained after application of the shift predictor; however, this was not significantly different at the 0.05 level. There were no differences in the shape of the correlograms. This suggests that the less time-consuming shift predictor-based stimulus-correction procedure can be used for cortical neurons. 4. Under stimulus conditions neural correlation coefficients could be < or = 50% smaller than for spontaneous conditions. The strength of the stimulus-corrected neural correlation was inversely related to the relative size of the stimulus predictor (compared with the neural synchrony) and thus to the effectiveness of stimulation. This suggests that the assumption of additivity of stimulus and connectivity effects on neural synchrony is generally violated both for shift predictor and PST predictor procedures. 5. The neural correlogram peaks were narrower for single-electrode pairs than for dual-electrode pairs both under stimulus and spontaneous conditions. Under stimulus conditions the peaks were generally narrower than under spontaneous firing conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗

Asymmetric hemodynamic responses of the human auditory cortex to monaural and binaural stimulation.

Applying whole-head functional magnetic resonance imaging (fMRI) in 11 neurologically intact subjects, hemodynamic responses to mon- or binaurally presented auditory stimuli were measured. To expand on previous studies in this research area, we used tones and consonant-vowel (CV) syllables. In one group of subjects (n=6) the perceived loudness of the monaurally presented stimuli were adjusted so that they matched the loudness of the binaurally presented stimuli. In a second group (n=5) no loudness adjustment was performed, thus the monaural stimuli were perceived less loud ( approximately 10 dB) than the binaural stimuli. These extensions allowed us to test whether CV syllables and tones produce different contralaterality effects (stronger hemodynamic responses in the auditory cortex contralateral to the stimulated ear) and whether binaural stimulation results in stronger activations in the auditory areas than during both monaural stimulation conditions (binaural summation) independent of loudness influences. In summary, we obtained the following findings: (1) strong contralaterality effects during monaural acoustic stimulation in the posterior superior temporal gyrus (STG) comprising the planum temporale and the dorsal bank of the superior temporal sulcus to CV syllables and tones; (2) the hemodynamic responses to contralaterally presented stimuli (during the monaural conditions) were mostly stronger than those to binaurally presented CV syllables; (3) there was no interaction between stimulus type and the size of the contralaterality effect; (4) there was no indication of binaural summation, rather we found stronger hemodynamic responses to the sum of both monaural stimulations (right and left ear) than to binaural stimulation in all auditory areas; (5) there were generally stronger hemodynamic responses to CV syllables than to tones in the posterior STG, while the hemodynamic responses to tones were stronger in the anterior part of the STG (temporal pole); and finally (6) there was no general difference in terms of hemodynamic response in the auditory cortex between the two groups when receiving either loudness-matched or non-loudness-matched monaural stimulation. These findings are discussed in the context of the underlying neurophysiological mechanisms, the peculiarities of functional fMRI, and the direct access and callosal relay models of hemispheric lateralization.

Acoustic Stimulation↗

Tonotopic features of speech-evoked activity in primate auditory cortex.

To further clarify the neural mechanisms underlying the cortical encoding of speech sounds, we have recorded multiple unit activity (MUA) in the primary auditory cortex (A1) and thalamocortical (TC) radiations of an awake monkey to 3 consonant-vowel syllables, /da/, /ba/ and /ta/, that vary in their consonant place of articulation and voice onset time (VOT). In addition, we have examined the responses to the syllables' isolated formants and formant pairs. Response features are related to the cortical tonotopic organization, as determined by examining the responses to selected pure tones. MUA patterns that differentially reflect the spectral characteristics of the steady-state formant frequencies and formant transition onset frequencies underlying consonant place of articulation occur at sites with similarly differentiated tone responses. Whereas the detailed spectral characteristics of the speech sounds are reflected in low frequency cortical regions, both low and high frequency areas generate responses that reflect their temporal characteristics of fundamental frequency and VOT. Formant interactions modulate the responses to the whole syllables. These interactions may sharpen response differences that reflect consonant place of articulation. Response features noted in A1 also occur in TC fibers. Thus, differences in the encoding of speech sounds between the thalamic and cortical levels may include further opportunities for formant interactions within auditory cortex. One effect could be to heighten response contrast between complex stimuli with subtle acoustical differences.

Acoustic Stimulation↗

A ventrorostral belt is adjacent to the guinea pig primary auditory cortex.

The previously defined anterior area (A) of guinea pig auditory cortex has been divided into a large dorsal portion identified as the primary area (AI) and a smaller ventrorostral belt (VRB). This division is based on: (1) the much longer response latency of units in VRB (21.7 ms) than AI (14.1 ms); (2) the absence of pure onset units in VRB (i.e. units that lacked a sustained response), which are common in AI; (3) the weakness of noise-induced evoked potentials in VRB compared to AI; (4) units in VRB had lower thresholds and stronger phase locking to amplitude modulated stimuli than in AI.

Animals↗

Independence of steady-state 40-Hz response and spontaneous 10-Hz activity in the human auditory cortex.

We recorded neuromagnetic signals from 5 subjects with a 24-channel planar SQUID gradiometer. Our aim was to search for any relationship between the 40-Hz steady-state responses and the spontaneous 10-Hz activity in the auditory cortex. Source strengths and locations of spontaneous activity were determined from spectral components of the data, and sources within the auditory cortex were determined by restricting the source location to a neighborhood of the auditory evoked response to single clicks. The characteristics of the 40-Hz steady-state responses were not simply related to those of the spontaneous 10-Hz activity, even within subjects, suggesting that these two oscillatory phenomena have independent generators.

Acoustic Stimulation↗

The response of single units in the auditory cortex of rhesus monkeys to predicted and to unpredicted sound stimuli.

Rhesus monkeys were trained to predict the nature of short auditory signals of two different types, to which they responded differentially. Prediction was based on visual signals that preceded the auditory ones. The monkey's use of the visual signals as predictors was assessed through two behavioural criteria. (1) performance in trials in which the visual signals was followed by the correct auditory signal (true conditioning) vs performance in trials in which the visual signal was followed by the wrong auditory signal (false conditioning). (2) Reaction time in trials with different types of conditioning. The response of single auditory cortex units to correctly and to incorrectly predicted auditory signals was recorded. The unconditioned response of every unit to each type of auditory stimulus was also obtained. Of 92 units that were analysed in detail, the response of about half was affected by the predictability of the stimulus. Units were affected in two different ways. One involved facilitation of the response to correctly predicted signals and inhibition of the response to incorrectly predicted signals. The other involved facilitation of the response to incorrectly predicted signals and base line response to correctly predicted signals. These findings were discussed in terms of neural mechanisms that relate to prediction.

Animals↗

Postnatal development of NR2A and NR2B mRNA expression in rat auditory cortex and thalamus.

Sensory cortex in the rat undergoes rapid postnatal development, especially following the onset of sensory function during so-called "critical periods." To investigate potential mechanisms in the auditory forebrain involving different NMDA receptor subunits, we have used in situ hybridization to determine expression patterns of NR2A and NR2B mRNA at postnatal days 4, 10, 13, 18, 25, and adult. In auditory cortex, NR2A mRNA expression is initially weak but increases rapidly over approximately 2 weeks. NR2B mRNA levels are initially high and remain high. For both subunits, expression tends to be highest in superficial layers of the cortex (except layer 1). Expression is weaker in the auditory thalamus (medial geniculate). Initially, NR2A mRNA expression is very low, whereas NR2B mRNA expression is moderate; both levels increase over approximately 2 weeks. Among medial geniculate subdivisions, NR2A mRNA expression occurs preferentially in the medial division, whereas NR2B mRNA expression is strongest in the ventral division. For auditory cortex and thalamus, NR2A and NR2B mRNA expression peaks about 1 week after the onset of hearing before declining slightly into adulthood. The heterogeneous distribution of NMDAR subunit mRNA throughout development may play a role in auditory forebrain development and function.

Aging↗

[Reactions of medial geniculate body neurons to stimulation of the auditory cortex].

Extra- and intracellular responses of pars principalis neurons in the medial geniculate body to stimulation of the first (AI), second (AII) and third (AIII) auditory cortex were studied in experiments on cats immobilized with d-tubocurarine. In geniculate neurons both antidromic (45-50%) and orthodromic (50-55%) reactions occurred in response to the auditory cortex stimulation. The latencies for antidromic and orthodromic responses were 0.3-2.5 ms and 2.0-ms, respectively. Late responses appeared with a latency of 30-200 ms. 63% of neurons responded antidromically to both AII and AI stimulation, that confirms the suggestion on the projection of a considerable number of the geniculate neurons to both auditory zones. Orthodromic responses of geniculate neurons consisted either of 1-2 spikes or a burst of 8-12 spikes with a frequency of 300-600/sec. The bursts are supposed to be the responses of inhibitory geniculate neurons. Intracellular recording showed the following responses: antidromic spikes, EPSP, EPSP-spike, EPSP-spike-IPSP, EPSP-IPSP and initial IPSP. Above 50% of initial IPSPs had the latency of 2.0-4.0 ms. They are supposed to be produced with the participation of intermediate inhibitory neurons located in the medial geniculate body.

Animals↗

Functional MRI of auditory cortex activated by multisite electrical stimulation of the cochlea.

Electrical stimulation of the ear of deaf patients via cochlear implants offers a unique occasion to study activity of central auditory pathways with fMRI, without bias due to scanner noise. Such measurements, however, require one to control the possible interference between fMRI acquisition and the implanted electrodes. A series of measurements on a customized phantom designed to characterize the level of induced currents during MRI acquisition is presented. These experiments demonstrate that the major artifactual contribution is due to radiofrequency interaction and that safe experimental conditions can be obtained with proper shielding of the stimulation cables. The induced currents could be reduced to low levels (<50 microA for a duration <2 ms), below the acoustic perceptual threshold of cochlear implant subjects. Subsequent fMRI experiments on a patient using an Ineraid cochlear implant were conducted. Results revealed bilateral localized activation of the primary auditory cortex. Stimulation of two different intracochlear electrodes elicited activity in two neighboring, but different, regions, in agreement with the known tonotopical organization of the auditory cortex. This work paves the way for fMRI studies of a broad selection of auditory paradigms without interference from unwanted noise.

Artifacts↗