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Ketamine blocks non-N-methyl-D-aspartate receptor channels attenuating glutamatergic transmission in the auditory cortex.

OBJECTIVE: To investigate the influence of ketamine on non-N-methyl-D-aspartate (NMDA) receptor-mediated synaptic transmission in the auditory cortex. MATERIAL AND METHODS: Using whole-cell patch-clamp techniques on pyramidal neurons, we studied the effects of ketamine on excitatory post-synaptic potentials (EPSPs) evoked by electrical stimulation of internal capsule fibers in slices of gerbil auditory cortex. RESULTS: After blockade of the slow, NMDA receptor-mediated EPSP component with DL-2-amino-5-phosphonovaleric acid, application of ketamine in a concentration-dependent manner led to a reduction in the amplitude of fast, 6-cyano-7-nitroquinoxalinedione (CNQX)-sensitive EPSPs, accompanied by an increased membrane resistance. Blockade of non-NMDA glutamate receptors with CNQX prevented both effects. CONCLUSION: Ketamine reduces membrane conductance and glutamatergic excitation, in part by blocking alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid receptor channels that may be constitutively active at a low level in slice preparations of auditory cortex.

Action Potentials↗

Left auditory cortex specialization for vertical harmonic structure of chords.

The representation of consonant and dissonant chords in the auditory cortex was investigated using low-noise functional magnetic resonance imaging and different experimental paradigms to separate the effects of vertical harmony from those of other musical features. The results revealed higher activation by consonant compared with dissonant chords in the left posterior auditory cortex, suggesting contributions of mechanisms of encoding the acoustical chord structure rather than mechanisms based on sequential integration of chords.

Acoustic Stimulation↗

Quantitative estimation of the primary auditory cortex in human brains.

Functional neuroimaging studies in humans are common worldwide. In order to determine with more accuracy both morphometric parameters and volume of the primary auditory cortex (PAC), we studied both right and left hemispheres in human control brains. Twelve hemispheres were systematically sectioned orthogonal to the anterior-posterior commissures (ac-pc line). Serial sections of the complete temporal lobe at 50 microm were obtained and stained with thionin (12 hemispheres) for cytoarchitectonic analysis. Four hemispheres were stained with the neuronal marker parvalbumin, a marker of primary sensory cortices. Morphometric analysis of the thionin-stained sections included size and shape factors as well as volume estimation using the Cavalieri method. Primary auditory areas extended for an average of 24 mm (twelve 2 mm apart sections); volume estimates determined by the Cavalieri method was 857+/-213 mm3 with a range of 658 mm3. The left primary auditory cortex was 7% greater than the right auditory cortex, without significant differences between hemispheres. The size and form of morphometric parameters obtained from each sampled section also revealed scarce differences between hemispheres, and the tendency to irregularity and ellipsoidity was more marked in the left hemisphere. No differences in size and form between right and left hemispheres were determined in our study. Morphometric analysis are of value in functional studies, specially those using non-invasive and lower resolution techniques such as Single Photon Emission Computed Tomography (SPECT).

Adolescent↗

Synaptic proliferation in the auditory cortex of the young adult rat following callosal lesions.

The long-term effects of partial deafferentation in the neocortex of adult rats were studied in four-month old rats in which the corpus callosum had been completely sectioned when they were one-month old. Quantitative light microscopy was used to identify morphological changes in the auditory cortex resulting from the loss of established callosal connections. Particular attention was directed at those cortical layers known to receive the heaviest callosal projection (layers II and III) and at neurons known to be postsynaptic to callosal afferents (layer V pyramidal neurons). The comparative analysis of both semithin plastic sections and Golgi-impregnated material from long-term, callosally-lesioned rats and age-matched control animals reveals no differences in the overall cortical thickness, the thickness of cortical layers, the numbers of neurons or the density of spines along apical dendrites of layer V pyramidal neurons. However, as a result of the callosal lesion, large diameter apical dendrites are significantly thinner in the callosally deafferented cortex and there is a small increase in the number of neuroglial cells in the deeper cortical layers. To determine whether another system of afferents to the auditory cortex spreads into the deafferented callosal domain, geniculate lesions were made in long-term, callosally-lesioned animals and age-matched controls. The terminal projection patterns of thalamic afferents were compared using the Fink-Heimer technique and quantitative electron microscopy. Normally in the auditory cortex there is only a small region of overlap between the terminal projection fields of callosal afferents and thalamic afferents, the latter projecting chiefly to layer IV and low layer III. However, three months after callosal lesions, thalamic axons had proliferated superficially into part of the callosal domain. Furthermore, in the normal auditory cortex after geniculate lesions, there were three rostrocaudally oriented bands of relatively dense thalamocortical terminal degeneration separated by regions of less dense degeneration. In the doubly lesioned animals these bands of degeneration were less distinct due to a proliferation of thalamic axons into the regions characterized by sparse projections.

Aging↗

Physiological and anatomical evidence for multisensory interactions in auditory cortex.

Recent studies, conducted almost exclusively in primates, have shown that several cortical areas usually associated with modality-specific sensory processing are subject to influences from other senses. Here we demonstrate using single-unit recordings and estimates of mutual information that visual stimuli can influence the activity of units in the auditory cortex of anesthetized ferrets. In many cases, these units were also acoustically responsive and frequently transmitted more information in their spike discharge patterns in response to paired visual-auditory stimulation than when either modality was presented by itself. For each stimulus, this information was conveyed by a combination of spike count and spike timing. Even in primary auditory areas (primary auditory cortex [A1] and anterior auditory field [AAF]), approximately 15% of recorded units were found to have nonauditory input. This proportion increased in the higher level fields that lie ventral to A1/AAF and was highest in the anterior ventral field, where nearly 50% of the units were found to be responsive to visual stimuli only and a further quarter to both visual and auditory stimuli. Within each field, the pure-tone response properties of neurons sensitive to visual stimuli did not differ in any systematic way from those of visually unresponsive neurons. Neural tracer injections revealed direct inputs from visual cortex into auditory cortex, indicating a potential source of origin for the visual responses. Primary visual cortex projects sparsely to A1, whereas higher visual areas innervate auditory areas in a field-specific manner. These data indicate that multisensory convergence and integration are features common to all auditory cortical areas but are especially prevalent in higher areas.

Acoustic Stimulation↗

Reactions of human auditory cortex to a change in tone duration.

Auditory evoked magnetic fields were measured using a stimulation sequence where repetitive identical tone bursts were randomly and infrequently replaced by shorter tones. The deviation in the stimulus duration evoked a specific response, the mismatch field, peaking about 130 ms after the end of the shorter stimulus. The response can be explained by neural activity at the supratemporal auditory cortex. The results suggest the existence of a neural mechanism specific to changes in sound duration.

Acoustic Stimulation↗

[Comparative study of interneuronal relations in the auditory cortex of awake and anesthetized cats].

The character of interneuronal relations in the auditory cortex of alert and anaesthetized cats (nembutal) with chronicly inplanted electrodes was studied with the method of statistic analysis of cross-intervals of the two impulse series. The analysis of the histograms, obtained by means of processing a neuronal activity, showed that nembutal did not eliminate the dependent relations between neurones and that in the majority of cases the types of these relations are either retained or supplemented with new components. Experiments with a reduced dose of nembutal permitted to trace in time the changes in the amount of the inhibitory and excitatory interrelations in the anaesthetized state, and to compare these changes to the changes in the frequency of spike activity. It was found that nembutal predominantly suppresses the activity of the neurones, generating small spikes. The number of inhibitory connections is reduced simultaneously. Such synchroneity permits to assume the participation of the neurones generating small spikes in the establishment of inhibitory interrelations in the cat auditory cortex.

Anesthesia, General↗

Prefrontal connections of the parabelt auditory cortex in macaque monkeys.

In the present study, we determined connections of three newly defined regions of auditory cortex with regions of the frontal lobe, and how two of these regions in the frontal lobe interconnect and connect to other portions of frontal cortex and the temporal lobe in macaque monkeys. We conceptualize auditory cortex as including a core of primary areas, a surrounding belt of auditory areas, a lateral parabelt of two divisions, and adjoining regions of temporal cortex with parabelt connections. Injections of several different fluorescent tracers and wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) were placed in caudal (CPB) and rostral (RPB) divisions of the parabelt, and in cortex of the superior temporal gyrus rostral to the parabelt with parabelt connections (STGr). Injections were also placed in two regions of the frontal lobe that were labeled by a parabelt injection in the same case. The results lead to several major conclusions. First, CPB injections label many neurons in dorsal prearcuate cortex in the region of the frontal eye field and neurons in dorsal prefrontal cortex of the principal sulcus, but few or no neurons in orbitofrontal cortex. Fine-grain label in these same regions as a result of a WGA-HRP injection suggests that the connections are reciprocal. Second, RPB injections label overlapping prearcuate and principal sulcus locations, as well as more rostral cortex of the principal sulcus, and several locations in orbitofrontal cortex. Third, STGr injections label locations in orbitofrontal cortex, some of which overlap those of RPB injections, but not prearcuate or principal sulcus locations. Fourth, injections in prearcuate and principal sulcus locations labeled by a CPB injection labeled neurons in CPB and RPB, with little involvement of the auditory belt and no involvement of the core. In addition, the results indicated that the two frontal lobe regions are densely interconnected. They also connect with largely separate regions of the frontal pole and more medial premotor and dorsal prefrontal cortex, but not with the extensive orbitofrontal region which has RPB and STGr connections. The results suggest that both RPB and CPB provide the major auditory connections with the region related to directing eye movements towards stimuli of interest, and the dorsal prefrontal cortex for working memory. Other auditory connections to these regions of the frontal lobe appear to be minor. RPB has connections with orbitofrontal cortex, important in psychosocial and emotional functions, while STGr primarily connects with orbital and polar prefrontal cortex.

Animals↗

Rapid development of learning-induced receptive field plasticity in the auditory cortex.

Classical conditioning induces frequency-specific receptive field (RF) plasticity in the auditory cortex after relatively brief training (30 trials), characterized by increased response to the frequency of the conditioned stimulus (CS) and decreased responses to other frequencies, including the pretraining best frequency (BF). This experiment determined the development of this CS-specific RF plasticity. Guinea pigs underwent classical conditioning to a tonal frequency, and receptive fields of neurons in the auditory cortex were determined before and after 5, 15, and 30 CS-US (unconditioned stimulus) pairings, as well as 1 hr posttraining. Highly selective RF changes were observed as early as the first 5 training trials. They culminated after 15 trials, then stabilized after 30 trials and 1 hr posttraining. The rapid development of RF plasticity satisfies a criterion for its involvement in the neural bases of a specific associative memory.

Animals↗

Burst-firing sharpens frequency-tuning in primary auditory cortex.

Frequency-tuning in 46 high-firing single units from primary auditory cortex of ketamine-anaesthetized cats was studied separately for isolated-spike firing and burst spike firing. The tuning curve for burst firing was significantly narrower than for the overall firing rate condition and, consequently, much narrower than for the isolated spikes. The burst firing was found in excess of that predicted from a modulated Poisson process, so the results cannot be explained on basis of a change in firing rate criterion. We propose that burst firing in auditory cortex may selectively enhance frequency tuning dynamically controlled by the behavioural state of the animal as well as its stimulus history. Thus burst firing may have functional implications for cortical processing.

Acoustic Stimulation↗

Ferrier and the study of auditory cortex.

David Ferrier was a British physician who studied the localization of function in the cerebral hemispheres during the latter half of the 19th century. Using stimulation and ablation techniques, Ferrier demonstrated that auditory cortex was located in the superior temporal gyrus of the monkey and that ablation of auditory cortex resulted in deafness. Although he was substantially correct, Ferrier's location of auditory cortex was not accepted by his contemporaries, and his observations of cortical deafness were, until recently, discounted by modern researchers. Just why his findings were rejected is of interest to the study of cortical function.

Auditory Cortex↗

Role of context in the expression of learning-induced plasticity of single neurons in auditory cortex.

Classical conditioning produces frequency-specific plasticity of receptive fields (RFs) of single neurons in cat auditory cortex (Diamond & Weinberger, 1986). In this article we show that although plasticity may be observed during both training trials and determination of RFs, it is usually expressed in a qualitatively different form (e.g., decreased response during conditioning vs. increased response to this same conditioned stimulus in the postconditioning RF). This differential expression of learning-induced plasticity provides evidence for a role of context in neurophysiological mechanisms of learning in auditory cortex. A model of cortical neurons functioning within a mosaic of influences is presented. The Functional Mosaic model views the induction and expression of plasticity as separate processes.

Animals↗

Three-dimensional analysis of spontaneous and thalamically evoked gamma oscillations in auditory cortex.

The purpose of this study was to investigate interactions among laminar cell populations producing spontaneous and evoked high-frequency (approximately 40 Hz) gamma oscillations in auditory cortex. Electrocortical oscillations were recorded using a 64-channel epipial electrode array and a 16-channel linear laminar electrode array while electrical stimulation was delivered to the posterior intralaminar (PIL) nucleus. Spontaneous gamma oscillations, and those evoked by PIL stimulation, are confined to a location overlapping primary and secondary auditory cortex. Current source-density and principal components analysis of laminar recordings at this site indicate that the auditory evoked potential (AEP) complex is characterized by a stereotyped asynchronous activation of supra- and infragranular cell populations. Similar analysis of spontaneous and evoked gamma waves reveals a close spatiotemporal similarity to the laminar AEP, indicating rhythmic interactions between supra- and infragranular cell groups during these oscillatory phenomena. We conclude that neural circuit interactions producing the laminar AEP onset in auditory cortex are the same as those generating evoked and spontaneous gamma oscillations.

Acoustic Stimulation↗

Intrinsic electrophysiology of neurons in thalamorecipient layers of developing rat auditory cortex.

During early postnatal life, several critical events contribute to the functional development of rat sensory neocortex. Thalamocortical innervation of sensory cortex is completed during the first postnatal week and extrathalamic innervation develops over the first several weeks. In auditory cortex, acoustic-evoked potentials first occur in week 2 and develop most rapidly over weeks 2-3. Thus, rapid functional maturation of cortical circuits in sensory cortex occurs during the second and third postnatal weeks. The electrophysiological properties of cortical neurons that receive afferent inputs during this time may play an important role in development and function. In this study we examined the intrinsic electrophysiology, including spiking patterns, of neurons in layers II/III and IV of auditory cortex during postnatal weeks 2 and 3. Many neurons displayed characteristics consistent with previous descriptions of response classes (regular spiking, fast spiking, intrinsic bursting). In addition, we identified two groups, Rectifying and On-spiking neurons, that were characterized by (i) brief spike trains in response to maintained intracellular depolarizations, and (ii) striking outward rectification upon depolarization. Unusually brief spike trains (1-2 spikes) and short spike latencies (<10 ms) further distinguished On-spiking from Rectifying cells. Biocytin labeling demonstrated that On-spiking and Rectifying cells could be either pyramidal or nonpyramidal neurons. The intrinsic physiology of these cell groups may play an important role in auditory cortex function.

Analysis of Variance↗

Phase-locked responses to pure tones in guinea pig auditory cortex.

Phase-locked responses to pure tones are a characteristic of most auditory cells at the level of the brain stem and allow sophisticated analyses based on coincidence detection. Phase-locking to tones has not previously been shown at the level of the auditory cortex in single unit studies. We have now identified phase-locked responses in 10% of low-frequency (< 1 kHz) units in the ventrorostral belt, a strip of cortex immediately ventral to the primary auditory area. All of these units showed phase-locking in their response to binaural tone pips of 60-200 Hz and showed narrow band pass characteristics within this range.

Acoustic Stimulation↗

Spatial representation of neural responses to natural and altered conspecific vocalizations in cat auditory cortex.

This study shows the neural representation of cat vocalizations, natural and altered with respect to carrier and envelope, as well as time-reversed, in four different areas of the auditory cortex. Multiunit activity recorded in primary auditory cortex (AI) of anesthetized cats mainly occurred at onsets (<200-ms latency) and at subsequent major peaks of the vocalization envelope and was significantly inhibited during the stationary course of the stimuli. The first 200 ms of processing appears crucial for discrimination of a vocalization in AI. The dorsal and ventral parts of AI appear to have different roles in coding vocalizations. The dorsal part potentially discriminated carrier-altered meows, whereas the ventral part showed differences primarily in its response to natural and time-reversed meows. In the posterior auditory field, the different temporal response types of neurons, as determined by their poststimulus time histograms, showed discrimination for carrier alterations in the meow. Sustained firing neurons in the posterior ectosylvian gyrus (EP) could discriminate, among others, by neural synchrony, temporal envelope alterations of the meow, and time reversion thereof. These findings suggest an important role of EP in the detection of information conveyed by the alterations of vocalizations. Discrimination of the neural responses to different alterations of vocalizations could be based on either firing rate, type of temporal response, or neural synchrony, suggesting that all these are likely simultaneously used in processing of natural and altered conspecific vocalizations.

Acoustic Stimulation↗

Age-related loss of the GABA synthetic enzyme glutamic acid decarboxylase in rat primary auditory cortex.

Age-related changes within the auditory brainstem typically include alterations in inhibitory neurotransmission and coding mediated by GABA and glycinergic circuits. As part of an effort to evaluate the impact of aging on neurotransmission in the higher auditory centers, the present study examined age-related changes in the GABA synthetic enzyme, glutamic acid decarboxylase (GAD), in rat primary auditory cortex (AI), which contains a vast network of intrinsic and extrinsic GABAergic circuits throughout its layers. Message levels of the two GAD isoforms found in brain, GAD(65) and GAD(67), and GAD(67) protein levels were compared in young adult, middle-aged and aged rats using in situ hybridization and quantitative immunocytochemistry, respectively. For comparison, age-related GAD changes were also assessed in the parietal cortex and hippocampus. Significant age-related decreases in GAD(65&67) messages were observed in AI layers II-VI of aged rats relative to their young adult cohorts. The largest changes were identified in layer II (GAD(65): -26.6% and GAD(67): -40.1%). GAD(67) protein expression decreased significantly in parallel with mRNA decreases in all layers of AI. Adjacent regions of parietal cortex showed no significant GAD(67) protein changes among the age groups, except in layer IV. As previously described, GAD(67) message and protein levels in selected hippocampal regions were significantly reduced in aged rats. Age-related GAD reductions likely reflect decreases in both metabolic and pre-synaptic GABA levels suggesting a plastic down-regulation of normal adult inhibitory GABA neurotransmission. Consistent with the present findings, functional studies in primate visual cortex and preliminary studies in AI find coding changes suggestive of altered inhibitory processing in aged animals. An age-related loss of normal adult GABA neurotransmission in AI would likely alter temporal coding properties and could contribute to the loss in speech understanding observed in the elderly.

Aging↗

Differential thresholds of local field potentials and unit discharges in rat auditory cortex.

Thresholds for responses to tone bursts in the primary auditory field of pentobarbital-anesthetized rat are significantly lower for local field potentials (5.60 dB+/-1.76 S.E.M.) than for multiple unit discharges (17.80 dB+/-3.17), recorded simultaneously from the same microelectrode. The characteristic frequencies (CFs) of local field potentials provide a good 'predictive' estimate of unit CFs at their higher thresholds. The findings are consistent with the view that local field potentials in the auditory cortex reflect summed synaptic potentials rather than cellular discharges.

Acoustic Stimulation↗