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What are the synaptic and cellular mechanisms by which stimulus context shapes cortical responses? In this issue of Neuron, Wehr and Zador describe intracellular recordings of responses to click pairs in rat primary auditory cortex (A1) and offer new insights into the successive roles of inhibition and synaptic depression in suppressing responses to the second click in many A1 neurons.
1. Reflexive head orienting responses (ORs) elicited by bursts of wide-band noise were investigated in cats after bilateral or unilateral ablation of the auditory cortex, and the cats' performance was compared with that of control cats. The OR was used as an indication of ability to orient toward the azimuthal direction of a source of sound. 2. To adequately test this ability, a unique combination of stimulus duration and position of the sound source was selected on each trial. Stimulus durations (0.1, 0.3, and 1.5 s) were selected so that the offset of a burst of noise occurred before, during, or after an OR. The stimuli were produced from speakers positioned approximately at the interaural horizontal plane within each quadrant of a cat's auditory field. The ORs were recorded on moving film and analyzed quantitatively. 3. In the control cats, the trajectory of the OR was characterized by a saccadic profile (rapid steplike movement, monophasic velocity, and biphasic acceleration). The accuracy of the OR varied directly with stimulus duration, suggesting that the response was modified by auditory feedback produced by a head movement during the stimulus. Corrective responses executed during long-duration (1.5 s) stimuli reduced residual mean error to < 7 degrees in each of the control animals. The mean error in orientation was smaller for sources located in the frontal sound field than for sources located behind the coronal plane the head (> 90 degrees). When brief (0.1 s) stimuli were presented behind the head, the cats confused back with front directions on most of the trials. 4. Compared with performance in the control cats, bilateral destruction of the auditory geniculocortical system severely impaired a cat's ability to orient consistently and accurately toward a source of sound. Latencies to the onset of ORs were increased, the magnitudes of ORs were reduced, average error in orienting to a sound source was larger under every stimulus duration-source position combination, relatively few corrective responses were executed, and residual mean error was significantly elevated (bilateral = 28.1 degrees; control = 3.1 degrees). Several animals with bilateral lesions also made vertical errors in orienting to azimuthal sources of sound. 5. However, in the bilateral lesion group, ORs were initiated in the correct right or left direction; and, rather than eliminating accurate responses altogether, the lesions reduced the probability of their occurrence. Furthermore, the saccadic profile of the response was preserved, providing evidence that the motor control system for the OR was not perturbed by the bilateral lesions.(ABSTRACT TRUNCATED AT 400 WORDS)
Recent neuroimaging and neuropsychological data suggest that speech perception is supported in bilaterally auditory areas. We evaluate this issue building on well-known behavioral effects. While undergoing positron emission tomography (PET), subjects performed standard auditory tasks: direction discrimination of frequency-modulated (FM) tones, categorical perception (CP) of consonant-vowel (CV) syllables, and word/non-word judgments (lexical decision, LD). Compared to rest, the three conditions led to bilateral activation of the auditory cortices. However, lateralization patterns differed as a function of stimulus type: the LD task generated stronger responses in the left, the FM task a stronger response in the right hemisphere. Contrasts between either words or syllables versus FM were associated with significantly greater activity bilaterally in superior temporal gyrus (STG) ventro-lateral to Heschl's gyrus. These activations extended into the superior temporal sulcus (STS) and the middle temporal gyrus (MTG) and were greater in the left. The same areas were more active in the LD than the CP task. In contrast, the FM task was associated with significantly greater activity in the right lateral-posterior STG and lateral MTG. The findings argue for a view in which speech perception is mediated bilaterally in the auditory cortices and that the well-documented lateralization is likely associated with processes subsequent to the auditory analysis of speech.
The corticofugal projection from 12 auditory cortical fields onto the medial geniculate body was investigated in adult cats by using wheat germ agglutinin conjugated to horseradish peroxidase or biotinylated dextran amines. The chief goals were to determine the degree of divergence from single cortical fields, the pattern of convergence from several fields onto a single nucleus, the extent of reciprocal relations between corticothalamic and thalamocortical connections, and to contrast and compare the patterns of auditory corticogeniculate projections with corticofugal input to the inferior colliculus. The main findings were that (1) single areas showed a wide range of divergence, projecting to as few as 5, and to as many as 15, thalamic nuclei; (2) most nuclei received projections from approximately five cortical areas, whereas others were the target of as few as three areas; (3) there was global corticothalamic-thalamocortical reciprocity in every experiment, and there were also significant instances of nonreciprocal projections, with the corticothalamic input often more extensive; (4) the corticothalamic projection was far stronger and more divergent than the corticocollicular projection from the same areas, suggesting that the thalamus and the inferior colliculus receive differential degrees of corticofugal control; (5) cochleotopically organized areas had fewer corticothalamic projections than fields in which tonotopy was not a primary feature; and (6) all corticothalamic projections were topographic, focal, and clustered, indicating that areas with limited cochleotopic organization still have some internal spatial arrangement. The areas with the most divergent corticothalamic projections were polysensory regions in the posterior ectosylvian gyrus. The projection patterns were indistinguishable for the two tracers. These findings suggest that every auditory thalamic nucleus is under some degree of descending control. Many of the projections preserve the relations between cochleotopically organized thalamic and auditory areas, and suggest topographic relations between nontonotopic areas and nuclei. The collective size of the corticothalamic system suggests that both lemniscal and extralemniscal auditory thalamic nuclei receive significant corticofugal input.
In vivo microdialysis offers a unique approach to monitor biochemical events related to brain function and metabolism, and has been used extensively in many systems to measure the release of endogenous transmitters and other neuroactive substances during normal and pathological conditions. The characterization of neurotransmitters' changes induced by salicylate in the inferior colliculus (IC) and the auditory cortex (AC) may provide insight into the action of salicylate on the auditory system and, through this, provide a better understanding of neurological mechanism of salicylate-induced tinnitus. In the present study, the effect of salicylate on 5-HT system in IC and AC has been monitored by microdialysis in salicylate-induced tinnitus animal models. Glucose and lactate levels in IC and AC were significantly increased after application of salicylate (350 mg/kg, i.p.), indicating a salicylate-related increase in regional neuronal activity. The 5-HT level increased to a maximum of 268+/-27% basal level in IC 2 h after application and of 277+/-24% basal level in AC around 3 h after application. These data suggest that the increases of 5-HT levels in IC and AC may be involved in the tinnitus generation.
The character of the interaction (Spearman's correlation coefficient) between the structures before, and during the development, extinction, and restoration of an instrumental food-procuring reflex, as well as during the automatization of the reflex was determined on the basis of the averaged sound-induced activity (AEP) of symmetrical points of the auditory cortex (AI) and the amygdalae (abl) of cats. The co-tuning of the cortex and the amygdalae during the adaptation of the animal was found to be individual in character; this was replaced by close interactions during the formation of the reflex and by the disruption of their correlatedness during its extinction. The consolidation of the reflex prior to the stage of automatization was accompanied by attenuation of the connections between the cortex and the amygdala. The results attest to the complex and dynamic character of the interdependence in the cortex-amygdala system during conditioned reflex activity.
The present study is concerned with the ability of muscarinic actions of acetylcholine (ACh) to modulate glutamate and gamma-aminobutyric acid (GABA)-mediated synaptic transmission in the in vitro rat auditory cortex. Whole-cell patch clamp recordings were obtained from layer II-III pyramidal neurons, and the fast-EPSP (AMPA/kainate), fast-IPSP (GABA(A)), and slow-IPSP (GABA(B)), were elicited following a stimulus to deep gray/white matter. Acetyl-beta-methylcholine (MCh), a muscarinic receptor agonist, applied by either superfusion or iontophoresis, produced an atropine-sensitive increase or decrease in the amplitude of the fast-EPSP. The effect of MCh could be predicted by the response of the fast-EPSP to paired-pulse stimulation (i.e. a conditioning pulse followed 300 ms later by a test pulse). The fast-EPSP was decreased in amplitude by MCh in cases where the test-EPSP was suppressed in the pre-MCh condition, and increased in amplitude when the test-EPSP was facilitated. The fast- and slow-IPSPs were always reduced by MCh. In several experiments, the strength of synaptic inhibition was systematically modified by varying stimulus intensity. When the fast-EPSP was elicited in the absence of IPSPs, it was decreased in amplitude by MCh. However, when the fast-EPSP was elicited in conjunction with large IPSPs it was increased in amplitude during MCh. Because the magnitude of the fast-EPSP is influenced by the degree of temporal overlap with IPSPs, it was hypothesized that enhancement of the fast-EPSP was the result of disinhibition produced as a consequence of muscarinic reduction of GABAergic IPSPs. This view was supported by the finding that MCh could reduce the amplitude of pharmacologically isolated GABAergic IPSPs (i.e. elicited in the absence of glutamatergic transmission). Our results suggest that ACh at muscarinic receptors can modify fast glutamatergic neurotransmission differently as a function of strength of inhibition, to suppress that produced by 'weak' inputs and enhance that produced by 'strong' inputs.
1. The physiology and topography of single neuron responses along the isofrequency domain of the middle- and high-frequency portions [characteristic frequencies (CFs) greater than 4 kHz] of the primary auditory cortex (AI) were investigated in the barbiturate-anesthetized cat. Single neurons were recorded at several locations along the extent of isofrequency contours, defined from initial multiple-unit mapping. For each neuron a high-resolution excitatory tuning curve was determined, and for some neurons high-resolution two-tone tuning curves were recorded to measure inhibitory/suppressive areas. 2. A physiologically distinct population of neurons was found in the dorsal part of cat AI. These neurons exhibited two or three distinct excitatory frequency ranges, whereas most neurons in AI responded with excitation to a single narrow frequency range. These were called multipeaked neurons because of the shape of their tuning curves. At frequencies between the excitatory regions, the multipeaked neurons were inhibited or unresponsive. 3. Multipeaked neurons exhibited several distinct threshold minima in their frequency tuning curves. Most of the multipeaked neurons (88%) displayed two frequency minima, whereas the rest exhibited three minima. 4. The frequency separation between threshold minima was less than 1 octave in 71% of the double-peaked neurons recorded. Occasionally, the frequency peaks of these neurons closely corresponded to a response to second and third harmonics without a response to the fundamental frequency. 5. Multipeaked neurons exhibited a wide range of total bandwidths (highest excitatory frequency minus lowest excitatory frequency expressed in octaves). Bandwidths of the isolated peaks within the same neuron were also quite variable. 6. Response latencies to tones with frequencies within each peak of a multipeaked neuron could vary considerably. In 71% (17) of the neurons, tones corresponding to the high-frequency peak (CFh) elicited a longer response latency (greater than 4 ms) than those corresponding to the low-frequency peak (CF1). 7. Inhibitory/suppressive bands, as demonstrated with a two-tone paradigm, were often present between the peaks. Typically, neurons with excitatory peaks of similar response latencies showed an inhibitory band located between the peaks. 8. Ninety percent of the topographically localized multipeaked neurons were in the dorsal part of AI (greater than 1 mm dorsal to the maximum in the sharpness-of-tuning map). Although these neurons were restricted to dorsal AI, only 35% of neurons in this region were multipeaked. 9. Multipeaked neurons could show decreased response latencies and thresholds to two-tone combinations.(ABSTRACT TRUNCATED AT 400 WORDS)
Synaptic plasticity in polysynaptic neural circuits permits modulation of the dynamic properties of these circuits. We investigated the properties of polysynaptic potentiation in pyramidal neurons in layer V of rat auditory cortex (AC) slices using the perforated patch clamp technique. The GABAA receptor inhibitor bicuculline was used to facilitate polysynaptic activity. The amplitude and duration of the polysynaptic activity were both gradually potentiated with repetitive stimulation (RS) at 12 s intervals. Potentiation was saturated within 10 min of the onset of RS. After the cessation of RS, the polysynaptic responses returned to control levels within 30 min. RS-induced potentiation was confirmed by fluorescence imaging of slices loaded with the Ca2+ indicator rhod-2. Such potentiation was not induced by stimulation at 60 s intervals. The magnitude of the RS-induced potentiation in layer V pyramidal neurons in the AC was greater than that in either layer II/III pyramidal neurons in the AC or layer V pyramidal neurons in the visual cortex. The NMDA receptor antagonist APV (100 microm), inhibited RS-induced potentiation. When stimulated at 1 Hz, the potentiated response appeared rapidly. In the absence of bicuculline, RS consisting of five pulses at 30 ms intervals, repeated at 12 s intervals for 10 min, elicited potentiation of firing activity, suggesting that the potentiation is independent of bicuculline. The present study demonstrates the dynamic properties of polysynaptic circuits involving layer V pyramidal neurons in the AC are strongly affected by activity-dependent synaptic potentiation.
Timbre and pitch are two independent perceptual qualities of sounds closely related to the spectral envelope and to the fundamental frequency of periodic temporal envelope fluctuations, respectively. To a first approximation, the spectral and temporal tuning properties of neurons in the auditory midbrain of various animals are independent, with layouts of these tuning properties in approximately orthogonal tonotopic and periodotopic maps. For the first time we demonstrate by means of magnetoencephalography a periodotopic organization of the human auditory cortex and analyse its spatial relationship to the tonotopic organization by using a range of stimuli with different temporal envelope fluctuations and spectra and a magnetometer providing high spatial resolution. We demonstrate an orthogonal arrangement of tonotopic and periodotopic gradients. Our results are in line with the organization of such maps in animals and closely match the perceptual orthogonality of timbre and pitch in humans.
We report the spectrotemporal response properties of single units in the primary (A1) and dorsocaudal (DC) fields, and the ventrorostral belt of the urethane-anaesthetised guinea pig auditory cortex. Using reverse correlation analysis, spectrotemporal receptive fields (STRFs) were constructed and subsequently classified according to a novel qualitative scheme that was based on the duration and bandwidth of excitatory and inhibitory regions within the STRF. The STRFs of units in both A1 and DC showed either broad-band (> or = 1 octave) or narrow-band (< 1 octave) excitatory and inhibitory regions occurring either alone or together. The excitatory regions were of short duration (lasting for <50 ms) or more sustained (up to about 100 ms) and inhibitory areas either followed excitation or were located as inhibitory sidebands along the high- and low-frequency edges of the excitatory regions. Inhibitory areas that followed excitatory regions were found to be either short lasting (10-20 ms) or longer lasting (up to 200 ms or more). The STRFs recorded from each cortical area indicated temporal response properties consistent with those shown by traditional peristimulus time histogram analysis. Overall, fields A1 and DC showed no significant differences in the distribution of STRF types. Thus, it appears that both fields display similar spectrotemporal sensitivities to auditory stimuli and therefore, appear to process such stimuli in a parallel fashion. Single units recorded in the ventrorostral belt area showed STRF types similar to those recorded in A1 and DC. However, the proportions of STRF types were significantly different, suggesting a difference in spectrotemporal processing between the ventrorostral belt and the core areas.
We present two patients with bilateral lesions of the superior temporal cortex who manifested a number of functional dissociations in the auditory domain. The perception of speech and environmental sounds were preserved; yet, the perception of tunes, prosody and voice was impaired. As the processing of melodic but not rhythmic variations in musical sequences was selectively disturbed, the deficit cannot be attributed to a general impairment in auditory memory or sequential processing. These findings suggest that melody processing is not mediated by a general-purpose auditory architecture but by specialized cortical subsystems residing within the lesioned areas. Current taxonomies of auditory agnosia and models of normal music cognition are evaluated in light of the functional dissociations manifested by these patients.
It has been shown that in all age groups of animals, self-stimulation of the hypothalamus is accompanied with the decrease in the latent period and the increase in the amplitude of the evoked potential (EP) in the auditory cortex. During negative stimulation, the increase in temporal parameters of the response takes place together with the decrease in the amplitude of the EP and the onset of secondary waves. Significant age changes were revealed in the recovery of the initial pattern of the EP after cessation of stimulation of emotiogenic zones. The recovery of the EP after stimulation of the "reward" zone in younger rabbits occurs 4 times faster than in adult animals, whereas in the former the recovery period of the EP after stimulation of the "punishment" zone is significantly longer.
Microelectrode mapping and horseradish peroxidase oxidase histochemistry were combined to study the relationship between the characteristic-frequency representation and the intrinsic connectivity of the primary auditory cortex in the cat. Small extracellular iontophoretic injections of horseradish peroxidase within the characteristic-frequency map resulted in labeling of neuronal processes that, in the tangential plane, radiated out asymmetrically from the injection site over distances of several millimeters. The heaviest concentration of labeled fibers was along an axis parallel with the orientation of the isofrequency line within which the injection had been made. Thus, primary field neurons that have the same or a similar characteristic frequency have the potential of being preferentially interconnected.
Quantitative analysis of layer-to-layer distribution of neurons and macrogliocytes in zones AI, AII, Ep and Ins of cat brain was performed in specimens stained after Einarson. Zones of auditory cortex were shown not to differ in density of neuron distribution. In every zone the neuron number in layers II, III and VI was significantly higher than in layers IV and V and in layers III and IV of zones AI and AII the number of neurons with macroglial satellites was almost twices higher than in the same layers of zones Ep and Ins. Fraction of neurons with different number of satellites shows significant diversities as well. In layers IV, V and VI of zones AI and AII both total number of macrogliocytes and perineuronal satellites was significantly higher than in zones Ep and Ins. The number of perineuronal satellitocytes correlates both with neuron axonal length and the level of the cell functional activity.
We measured reflectance changes by means of optical imaging of intrinsic signals to study the effects of acute electrical cochlear stimulation on the topography of the cat auditory cortex. After single-pulse electrical stimulation at selected sites of a multichannel implant device, we found topographically restricted response areas representing mainly the high-frequency range in AI. Systematic variation of the stimulation pairs and thus of the cochlear frequency sites revealed a systematic and corresponding shift of the response areas that matched the underlying frequency organization. Intensity functions were usually very steep. Increasingly higher stimulation currents evoked increasingly larger response areas, resulting in decreasing spatial, i.e. cochleotopic, selectivity; however, we observed only slight positional shifts of the focal zones of activity. Electrophysiological recordings of local field potential maps in the same individual animals revealed close correspondence of the locations of the cortical response areas. The results suggest that the method of optical imaging can be used to map response areas evoked by electrical cochlear stimulation, thereby maintaining a profound cochleotopic selectivity. Further experiments in chronically stimulated animals will shed more light on the degree of functional and reorganizational capacities of the primary cortex and could be beneficial for our understanding of the treatment of profound deafness.
1. The influence of sound pressure level (SPL) at the two ears was studied in single-neuron responses recorded in high-frequency regions of primary auditory cortex (AI) of anesthetized cats. For each unit, many binaural combinations of SPL were tested by using best-frequency tone pips presented to each ear independently via sealed stimulus delivery systems. In the preceding paper, we illustrated the different forms of response observed in our sample of units. Here we explore in more detail the mechanisms underlying the properties of the largest single class of binaural response, characterized by joint nonmonotonic tuning to the SPLs at the two ears. We have described such units as being influenced by a Two-Way Intensity Network (TWIN). 2. Under binaural conditions, 62% of our sample of well documented neurons (81/130) exhibited a nonmonotonic relation between response magnitude and the SPL at one or the other ear. Of these units, 47 displayed clear bilateral nonmonotonicity (TWIN tuning), 17 units displayed only unilateral nonmonotonicity, and an additional 17 units showed intermediate (or transitional) characteristics between unilateral and bilateral nonmonotonicity. These characteristics can also be described in terms of average binaural level (ABL) and interaural level difference (ILD). Thus there is commonly a nonmonotonic relation between response magnitude and ABL and sometimes a TWIN tuning to ABL and ILD. The distribution of best frequencies for TWIN neurons is broad. 3. Under monaural conditions, TWIN neurons exhibit diverse properties. Some are responsive only under binaural conditions [i.e., predominantly binaural (PB)]. Some monaurally responsive TWINs are contralaterally excitable and ipsilaterally unresponsive (EO), some are ipsilaterally excitable and contralaterally unresponsive (OE), and a few are bilaterally excitable (EE). Monaural rate/level functions are monotonic for some of these neurons and nonmonotonic for others. Neurons of the PB class have previously been found to have nonmonotonic selectivity for ILDs near zero. In this study we have found that virtually all PB neurons are also nonmonotonically selective for ABL with different PB neurons having different best ABLs. 4. For TWIN neurons that respond monaurally, it is possible to demonstrate a mixed binaural influence. The optimal stimulus (or best binaural combination) for a TWIN neuron is associated with binaural facilitation. Flanking the most effective combination of ABL and ILD are less effective combinations that generate lower response magnitudes, either through threshold effects (at low SPLs) or through binaural suppression (at higher SPLs).(ABSTRACT TRUNCATED AT 400 WORDS)
1. Preliminary to studying the organization of azimuthal sensitivity of neurons along frequency-band strips in the primary auditory cortex (AI) of cat (see companion paper), this study examined the sensitivity of 251 units in cat AI to variations in the azimuthal location of sound sources in the frontal hemifield. Most units (231) were tested with tones at the characteristic frequency (CF; frequency to which the unit had the lowest threshold). Unit CFs ranged from 5 to 36 kHz. A large number of units (91) were tested with broadband noise stimuli, and a few units were also tested at other frequencies within the cell's tuning response area. 2. When tested at stimulus intensities 20-30 dB above CF or noise threshold, the different forms of azimuthal sensitivity exhibited by AI neurons could be divided into (1) contra-field azimuth functions; (2) ipsi-field functions; (3) central-field functions; (4) omnidirectional functions, and (5) multipeaked functions. Contra-field azimuth functions were the most prevalent, with 45.9% of units tested with CF tones and 42.9% of units tested with noise exhibiting this type of azimuthal sensitivity. Ipsi-field azimuthal sensitivity was found in 16.9% of units tested with CF tones and 19.8% of units tested with noise. Central-field azimuthal sensitivity was seen in 10.8% of units tested with CF tones and 17.6% of units tested with noise. Omnidirectional azimuthal sensitivity was seen in 19.9% of units tested with CF tones and 17.6% of units tested with noise, whereas multipeaked azimuthal sensitivity was found in 6.5% of units tested with CF tones and 5.5% of units tested with noise. 3. The effects of increasing stimulus intensity on azimuthal sensitivity were examined in 185 units tested with CF tones and 67 units tested with noise. For four major classes of azimuthal sensitivity (contra-field, ipsi-field, central-field and omnidirectional), the most common effect (approximately 60% of each class) was for the azimuth function to remain constant in form by the defining criteria for these classes. The next most common effect for all classes except omnidirectional azimuth functions was for an expansion of the azimuthal range eliciting responses. (The definition of omnidirectionality precluded any expansion of the response range in this class of azimuth function). A smaller number of units in some classes showed a compression of the azimuth function to a smaller response range, and others showed more complex expansive and compressive effects with increasing stimulus intensity.(ABSTRACT TRUNCATED AT 400 WORDS)