RESUMEN
Recordings of spike trains made with microwires or silicon electrodes include more noise from various sources that contaminate the observed spike shapes compared with recordings using sharp microelectrodes. This is a particularly serious problem if spike shape sorting is required to separate the several trains that might be observed on a particular electrode. However, if recordings are made with an array of such electrodes, there are several mathematical methods to improve the effective signal (spikes) to noise ratio, thus considerably reducing inaccuracy in spike detection and shape sorting. We compare the theoretical basis of three such methods and evaluate their performance with simulated and real data.
Asunto(s)
Potenciales de Acción/fisiología , Algoritmos , Artefactos , Electrodos/normas , Electrofisiología/métodos , Neurofisiología/métodos , Procesamiento de Señales Asistido por Computador/instrumentación , Animales , Sistema Nervioso Central/fisiología , Electrofisiología/instrumentación , Neuronas/fisiología , Neurofisiología/instrumentaciónRESUMEN
In this paper, we review recent work on aspects of corticothalamic interactions in the auditory and in the visual systems. There are gross similarities in the arrangements of these systems, but considerable contrasts in the processing computations and in the effects of corticothalamic feedback.
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Corteza Cerebral/fisiología , Tálamo/fisiología , Animales , Corteza Auditiva/fisiología , Retroalimentación , Cuerpos Geniculados/fisiología , Audición/fisiología , Modelos Neurológicos , Vías Nerviosas/fisiología , Corteza Visual/fisiologíaRESUMEN
In common with other sensory cortices, the mammalian primary auditory cortex (AI) demonstrates the capacity for large-scale reorganization following many experimental situations. For example, training animals in frequency-discrimination tasks has been shown to result in an increase in cortical frequency representation. Such central changes-most commonly, an increase in central representation of specific stimulus parameters-have been hypothesized to underlie the improvements in perceptual acuity (perceptual learning) seen in many learning situations. The actual behavioral relevance of central reorganizations, however, remains speculative. Here, we directly examine this issue. We first show that stimulating the AI cortex of the awake rat with a weak electric current (intracortical microstimulation or ICMS) has the effect of inducing central reorganizations similar to those accompanying the traditional plasticity experiments (a result previously noted only in anesthetized preparations). Depending on the site of AI stimulation, ICMS enlarged the cortical representation of certain frequencies. Next we examined the direct perceptual consequences of ICMS-induced AI reorganization for the rat's ability to discriminate frequencies. Over the course of the experiment, we also detailed, and made comparisons between, the frequency-response characteristics of rat AI cortex in the awake and ketamine-anesthetized animal. AI cells that responded to pure tones were divided into two categories--strongly and weakly responsive--based on the strength of their evoked discharge. Individual cells maintained their respective response strengths in both awake and anesthetized conditions. Strongly responsive cells showed at least four different temporal responses and tended to be narrowly tuned. Their responses were stable over the long term. In general frequency-response characteristics were qualitatively similar in the anesthetized and awake animal; bandwidths tended to be broader in awake animals. Although both strong and weak cell populations respond to tones, only the strongly responsive cells fit into a tonotopically organized scheme. By contrast, weakly responsive cells did not exhibit a frequency mapping and may represent a more diffuse input to AI than that underlying strongly responsive cells. In general, the overall frequency organization of AI was found to be equally well expressed in both the awake and anesthetized rat. ICMS reorganization of AI did not alter frequency-discrimination behavior in the rat--either signal detectability or response bias--suggesting that an increase in central representation, by itself, is insufficient to account for perceptual learning. It is likely that cortical reorganizations that accompany perceptual learning are strongly keyed to specific behavioral contexts.
Asunto(s)
Corteza Auditiva/fisiología , Plasticidad Neuronal/fisiología , Percepción de la Altura Tonal/fisiología , Estimulación Acústica , Animales , Corteza Auditiva/citología , Concienciación/fisiología , Conducta Animal/fisiología , Aprendizaje Discriminativo/fisiología , Estimulación Eléctrica , Femenino , Neuronas/fisiología , Ratas , Ratas Endogámicas , Tiempo de Reacción/fisiologíaRESUMEN
Neurons often work together to compute and process information, and neural assemblies arise from synaptic interactions and neural circuits. One way to study neural assemblies is to simultaneously record from several or many neurons and study the statistical relations among their spike trains. From this analysis researchers can try to understand the nature of the assemblies, which can also lead to attempts at modeling the underlying mechanisms. In this review we discuss three important parts of this process: (1) technical issues related to simultaneously recording more than one single unit, (2) ways of analyzing the data and (3) recent models offering hypothetical mechanisms of neural assemblies, especially models which incorporate feedback.
Asunto(s)
Potenciales de Acción/fisiología , Sistema Nervioso Central/fisiología , Modelos Neurológicos , Red Nerviosa/fisiología , Neuronas/fisiología , Algoritmos , Animales , Retroalimentación/fisiología , HumanosRESUMEN
It is often of interest experimentally to assess how synchronization between two neurons changes following a stimulus or other behaviorally relevant marker. The joint peristimulus time histogram (JPSTH) achieves this, but assumes that changes in the cells' firing rate following the stimulus are stereotyped from one sweep to the next. Erroneous results can be generated if this is not the case. We here present a method to assess whether there are variations in response latency or amplitude from sweep to sweep. We then describe how the effects of response latency variation can be mitigated by realigning sweeps to their individual latencies. Three methods of detecting response latency are presented and their performance compared on simulated data. Finally, the effect on the JPSTH of sweep realignment using detected latencies is illustrated.
Asunto(s)
Simulación por Computador , Modelos Neurológicos , Neuronas/fisiología , Tiempo de Reacción/fisiología , Animales , Teorema de Bayes , Encéfalo/fisiologíaRESUMEN
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.
Asunto(s)
Corteza Auditiva/fisiología , Discriminación de la Altura Tonal/fisiología , Animales , Corteza Auditiva/efectos de los fármacos , Conducta Animal/fisiología , Potenciales Evocados Auditivos/efectos de los fármacos , Potenciales Evocados Auditivos/fisiología , Femenino , Agonistas del GABA/farmacología , Mamíferos , Muscimol/farmacología , Discriminación de la Altura Tonal/efectos de los fármacos , RatasRESUMEN
Long-term modification of cortical receptive field maps follows learning of sensory discriminations and conditioned associations. In the process of determining whether appetitive - as opposed to aversive - conditioning is effective in causing such plastic changes, it was discovered that multineuron receptive fields, when measured in rats under ketamine-sedation, vary substantially over the course of a week, even in the absence of classical conditioning and electrode movement. Specifically, a simple correlation analysis showed that iso-intensity frequency response curves of multiunit clusters and local field potentials recorded from auditory cortex are nonstationary over 7 days. Nevertheless, significant plastic changes in receptive fields, due to conditioned pairing of a pure tone and electrical stimulation of brain reward centres, are detectable above and beyond these spontaneous daily variations. This finding is based on a novel statistical plasticity criterion which compares receptive fields recorded for three days before and three days after conditioning. Based on a more traditional criterion (i.e. one day before and after conditioning), the prevalence of learning-induced changes caused by appetitive conditioning appears to be comparable to that described in previous studies involving aversive conditioning.
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Apetito/fisiología , Corteza Auditiva/fisiología , Ritmo Circadiano , Condicionamiento Clásico/fisiología , Plasticidad Neuronal/fisiología , Estimulación Acústica , Potenciales de Acción/fisiología , Animales , Estimulación Eléctrica , Femenino , Aprendizaje/fisiología , Percepción de la Altura Tonal/fisiología , Ratas , RecompensaRESUMEN
We outline two improvements to the technique of gravitational clustering for detection of neuronal synchrony, which are capable of improving the method's detection of weak synchrony with limited data. The advantages of the enhancements are illustrated using data with known levels of synchrony and different interspike interval distributions. The novel simulation method described can easily generate such test data. An important dependence of the sensitivity of gravitational clustering to the interspike interval distribution of the analysed spike trains is described.
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Análisis por Conglomerados , Simulación por Computador , Modelos Neurológicos , Neuronas/fisiología , Transmisión Sináptica/fisiología , Potenciales de Acción , Algoritmos , Animales , Dinámicas no Lineales , Factores de TiempoRESUMEN
We have previously developed a model of the corticogeniculate system to explore cortically induced synchronization of lateral geniculate nucleus (LGN) neurons. Our model was based on the experiments of Sillito et al. Recently Brody discovered that the LGN events found by Sillito et al. correlate over a much longer period of time than expected from the stimulus-driven responses and proposed a cortically induced slow covariation in LGN cell membrane potentials to account for this phenomenon. We have examined the data from our model, and we found, to our surprise, that the model shows the same long-term correlation. The model's behavior was the result of a previously unsuspected oscillatory effect, not a slow covariation. The oscillations were in the same frequency range as the well-known spindle oscillations of the thalamocortical system. In the model, the strength of feedback inhibition from the cortex and the presence of low-threshold calcium channels in LGN cells were important. We also found that by making the oscillations more pronounced, we could get a better fit to the experimental data.
Asunto(s)
Cuerpos Geniculados/fisiología , Modelos Neurológicos , Corteza Visual/fisiología , Simulación por Computador , Electrofisiología , Oscilometría , Factores de TiempoRESUMEN
An increasing number of laboratories are studying population properties of the nervous system using data where the spike activity of more than one neuron is recorded on each electrode and where, accidentally or deliberately, these activities are not resolved into single unit spike trains. We have previously examined the consequences for measurement of cross-correlation between two such electrodes in the limited case where all individual distant (between electrode) correlations are the same and all individual close (on a single electrode) correlations are the same [Bedenbaugh, P.H., and Gerstein, G.L. (1997). Multiunit normalized cross correlation differs from the average single-unit normalized correlation. Neural Computation 9, 1265-1275]. Here, we lift these unrealistic restrictions to allow all values of individual correlation, and examine explicitly the cases of two or three unresolved neurons on each electrode. In these situations, the cross-correlation coefficient measured between the electrodes is a linear sum of the distant correlations, divided by a non-linear function of the close correlations. We then examine in detail the case of a single direct distant correlation and take account of all relevant indirect correlations. The measured interelectrode correlation shows a reduction of this actual distant correlation by a non-linear function of the close correlations on each electrode over most of their possible values. Finally, we examine the consequences of poor waveform sorting for correlation measures; here a supposedly isolated spike train is contaminated by some fraction of the activity of another train, a situation that unfortunately is all too common in experiments. All these distortions become far more serious in the more realistic situation of dynamic firing rates and correlations. This paper is intended as a cautionary note for those who want to draw inferences about neuronal organization and/or coding or representation by using cross-correlation analysis of unresolved recordings.
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Biología Computacional/métodos , Electrofisiología/métodos , Microelectrodos/normas , Neuronas/fisiología , Animales , Biología Computacional/instrumentación , Biología Computacional/normas , Electrofisiología/instrumentación , Electrofisiología/normas , Humanos , Modelos Neurológicos , Red Nerviosa/fisiología , Sistema Nervioso , Neuronas/citologíaRESUMEN
We have modeled biologically realistic neural networks that may be involved in contextual modulation of stimulus responses, as reported in the neurophysiological experiments of Motter (1994a, 1994b) (Journal of Neuroscience, 14:2179-2189 and 2190-2199). The networks of our model are structured hierarchically with feedforward, feedback, and lateral connections, totaling several thousand cells and about 300,000 synapses. The contextual modulation, arising from attention cues, is explicitly modeled as a feedback signal coming from the highest-order cortical network. The feedback signal arises from mutually inhibitory neurons with different stimulus preferences. Although our model is probably the simplest one consistent with available anatomical and physiological evidence and ignores the complexities that may exist in high-level cortical networks such as the prefrontal cortex, it reproduces the experimental results quite well and offers some guidance for future experiments. We also report the unexpected observation of 40 Hz oscillations in the model.
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Atención/fisiología , Red Nerviosa/fisiología , Corteza Visual/fisiología , Potenciales de Acción/fisiología , Animales , Macaca , Modelos Neurológicos , Red Nerviosa/citología , Neuronas/fisiología , Estimulación Luminosa/métodos , Tiempo de Reacción/fisiología , Corteza Visual/citologíaRESUMEN
Recent experimental work has provided evidence that trial-to-trial variability of sensory-evoked responses in cortex can be explained as a linear superposition of random ongoing background activity and a stationary response. While studying single trial variability and state-dependent modulation of evoked responses in auditory cortex of ketamine/xylazine-anesthetized rats, we have observed an apparent violation of this model. Local field potential and unit spike trains were recorded and analyzed during different anesthesia depths-deep, medium, and light-which were defined by the pattern of ongoing cortical activity. Estimation of single trial evoked response was achieved by considering whole waveforms, rather than just one or two peak values from each wave. Principal components analysis was used to quantitatively classify waveforms on the basis of their time courses (i.e., shapes). We found that not only average response but also response variability is modulated by depth of anesthesia. Trial-to-trial variability is highest under medium levels of anesthesia, during which ongoing cortical activity exhibits rhythmic population bursting activity. By triggering the occurrence of stimuli from the spontaneously occurring burst events, we show that the observed variability can be accounted for by the background activity. In particular, the ongoing activity was found to modulate both amplitude and shape (including latency) of evoked local field potentials and evoked unit activity in a manner not predicted by linear superposition of background activity and a stereotyped evoked response. This breakdown of the linear model is likely attributable to rapid transitions between different levels of thalamocortical excitability (e.g., spike-wave discharges), although brain "state" is relatively fixed.
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Corteza Auditiva/fisiología , Potenciales Evocados Auditivos/fisiología , Estimulación Acústica , Anestesia , Anestésicos Disociativos , Animales , Femenino , Ketamina , Ratas , Tiempo de Reacción/fisiología , XilazinaRESUMEN
Whether cortical neurons act as coincidence detectors or temporal integrators has implications for the way in which the cortex encodes information--by average firing rate or by precise timing of action potentials. In this study, we examine temporal coding by a simple passive-membrane model neuron responding to a full spectrum of multisynaptic input patterns, from highly coincident to temporally dispersed. The temporal precision of the model's action potentials varies continuously along the spectrum, depends very little on the number of synaptic inputs, and is shown to be tightly correlated with the mean slope of the membrane potential preceding the output spikes. These results are shown to be largely independent of the size of postsynaptic potentials, of random background synaptic activity, and of shape of the correlated multisynaptic input pattern. An experimental test involving membrane potential slope is suggested to help determine the basic operating mode of an observed cortical neuron.
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Corteza Cerebral/fisiología , Modelos Neurológicos , Neuronas/fisiología , Potenciales de Acción , Animales , Dendritas , Potenciales Postsinápticos Excitadores , Potenciales de la Membrana , Programas Informáticos , Sinapsis/fisiología , Transmisión SinápticaRESUMEN
The frequency-discrimination behavior of rats in a simple go/no-go task was analyzed using the theory of signal detection. Discrimination acuity was studied and the receiver operating characteristic (ROC) was generated in subjects by varying the reinforcement schedule and signal probability. The detectability indices d', A', and sensitivity index (SI) and response-bias indices B" and responsivity index (RI) were used to describe behavior. A' gave the most suitable psychometric functions while RI best described response-bias behavior. Weber ratios were 6.25% +/- 0.23% at 5 kHz in three subjects. The best method to obtain the ROC was to vary the probability with which subjects were reinforced. The ROC in two subjects demonstrated classical forms; in another subject, the function was asymmetric to the extent that detectability was not independent of response bias. Subjects altered their decision criterion in reporting a signal from trial to trial depending on previous trial events. On any given trial, subjects made a decision in one of several "decision states." Variables that influenced decision states included previous reinforcement and timeouts. The data indicate that timeouts may not be a useful feature in go/no-go tasks. The identification of multiple-decision states within a single behavioral session is a convenient method to generate the ROC without expressly manipulating experimental conditions.
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Percepción Auditiva/fisiología , Ecolocación/fisiología , Ratas Wistar/fisiología , Animales , Toma de Decisiones , Aprendizaje Discriminativo/fisiología , Femenino , Modelos Biológicos , Psicofísica , Curva ROC , Ratas , Esquema de RefuerzoRESUMEN
Recently Sillito et al. (Nature 1994;369:479-82) discovered correlations in the spike trains of a relatively distant pair of cat lateral geniculate nucleus cells when simultaneously stimulated by a drifting grating; no such correlation occurs when the visual cortex is removed. In a further analysis of the data, we have found that short, high-frequency bursts contribute substantially to the synchronization and we hypothesize that the origin of the bursts is the low-threshold calcium spike. Guided by this hypothesis, our model of the corticogeniculate pathway and early visual system reproduces the experimental data in nearly every detail, as well as making predictions about cortical activity during the synchronizing process. We also discuss the possible behavioral relevance of correlations in the geniculo-cortical loop as well as other neural systems.
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Canales de Calcio/fisiología , Cuerpos Geniculados/fisiología , Corteza Visual/fisiología , Potenciales de Acción/fisiología , Animales , Gatos , Modelos Neurológicos , Percepción de Movimiento/fisiología , Inhibición Neural , Reconocimiento Visual de Modelos/fisiología , Vías VisualesRESUMEN
Studies were carried out in rats anesthetized with ketamine or nembutal, with recording of multicellular activity (with separate identification of responses from individual neurons) in the primary auditory cortex before and after electrical intracortical microstimulation. These experiments showed that about half of the set of neurons studied produced responses to short tonal bursts, these responses having two components-initial discharges arising in response to the sound, and afterdischarge occurring after pauses of 50-100 msec. Afterdischarges lasted at least several seconds, and were generally characterized by a rhythmic structure (with a frequency of 8-12 Hz). After electrical microstimulation, the level of spike activity increased, especially in afterdischarges, and this increase could last up to 4 h. Combined peristimulus histograms, cross-correlations, and gravitational analyses were used to demonstrate interactions of neurons, which increased after electrical stimulation and were especially pronounced in the response afterdischarges.
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Corteza Auditiva/fisiología , Estimulación Acústica , Potenciales de Acción/fisiología , Animales , Corteza Auditiva/citología , Estimulación Eléctrica , Potenciales Evocados Auditivos/fisiología , Neuronas/fisiología , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
Frequency discrimination was investigated in the albino rat using a modified go/no-go positive reinforcement procedure in which subjects reported frequency increments in an ongoing series of pure tone bursts. Weber ratios (frequency difference limen/frequency) were measured from 5 to 32 kHz at 50 dB sound pressure level. A signal detection analysis of the procedure enabled a direct comparison to be made with the rat's performance in a discrete trial go/no-go task. A mean Weber ratio of 3.06+/-0.44% was measured in the frequency range 5-32 kHz. This indicates that the rat has better frequency discrimination acuity than has previously been thought. The result is discussed in the context of factors affecting performance. Among the factors that were explored we found that long training times and the specific training paradigm played important roles. In comparison to discrete trial go/no-go paradigms, rats performed much better when detecting signals from a repeating background. Frequency discrimination performance decreased linearly for tones less than 50 ms in duration. For longer tone duration performance was unaffected. The means and variability of reaction times for threshold changes of frequency were greater in comparison with supra-threshold frequency changes.
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Discriminación de la Altura Tonal/fisiología , Ratas/fisiología , Estimulación Acústica/métodos , Animales , Femenino , Psicofísica/métodos , Ratas Wistar , Tiempo de Reacción/fisiología , Factores de TiempoRESUMEN
Models of brain function predict that the recurrence of a process or state will be reflected in repeated patterns of correlated activity. Previous work on medullary raphe assembly dynamics revealed transient changes in impulse synchrony. This study tested the hypothesis that these variations in synchrony include distributed nonrandom patterns of association. Spike trains were recorded simultaneously in the ventrolateral medulla, n. raphe obscurus, and n. raphe magnus of four anesthetized (Dial), vagotomized, paralyzed, and artificially ventilated adult cats. The "gravitational" representation of spike trains was used to detect moments of impulse synchrony in neuronal assemblies visualized as variations in the aggregation velocities of particles corresponding to each neuron. Template matching algorithms were developed to identify excessively repeating patterns of particle condensation rates. Repeating patterns were detected in each animal. The reiterated patterns represented an emergent property not apparent in either corresponding firing rate histograms or conventional gravity representations. Overlapping subsets of neurons represented in different patterns were unmasked when the template resolution was changed. The results demonstrate repeated transient network configurations defined by the tightness and duration of synchrony in different combinations of neurons and suggest that multiple information streams are conveyed concurrently by fluctuations in the synchrony of on-going activity.
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Redes Neurales de la Computación , Neuronas/fisiología , Algoritmos , Animales , Presión Sanguínea/fisiología , Gatos , Interpretación Estadística de Datos , Femenino , Masculino , Modelos Neurológicos , Nervio Frénico/fisiología , VagotomíaRESUMEN
As the technology for simultaneously recording from many brain locations becomes more available, more and more laboratories are measuring the cross-correlation between single-neuron spike trains, and between composite spike trains derived from several undiscriminated cells recorded on a single electrode (multiunit clusters). The relationship between single-unit correlations and multiunit cluster correlations has not yet been fully explored. We calculated the normalized cross-correlation (NCC) between single-unit spike trains and between small clusters of units recorded in the rat somatosensory cortex. The NCC between small clusters of units was larger than the NCC between single units. To understand this result, we investigated the scaling of the NCC with the number of units in a cluster. Multiunit cross-correlation can be a more sensitive detector of neuronal relationship than single-unit cross-correlation. However, changes in multiunit cross-correlation are difficult to interpret uniquely because they depend on the number of cells recorded on each electrode and because they can arise from changes in the correlation between cells recorded on a single electrode or from changes in the correlation between cells recorded on two electrodes.
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Potenciales de la Membrana/fisiología , Corteza Somatosensorial/fisiología , Animales , Modelos Neurológicos , Ratas , Estadística como AsuntoRESUMEN
Many manipulations are able to change or perturb various aspects of single neuron properties and interneuronal relationships. Changes of cerebral cortex organization have been observed in different cortical areas and at different time scales in relation to peripheral stimulation, peripheral damage, associative learning, and electrical stimulation. Here we describe studies on separable multineuron recordings in the rat's auditory cortex under two different anesthetics. Acoustic stimuli were used as a normal, physiological input, and weak electrical intracortical microstimulation (ICMS) as a perturbation that forces a rapid cortical reorganization. ICMS induced fast changes in the cortical map and in the receptive field properties of cells at the electrically stimulated and adjacent electrodes. In effect there was an enlargement of the cortical domain tuned to the acoustic frequency that had been represented at the stimulating electrode. ICMS also incremented afterdischarge responses; these consisted of an initial response to the auditory stimulus followed by less intense repetitive activity that was stimulus-time locked and had a period of 8-12 Hz, similar to that of the spontaneous synchronous activity. Cortical activity under ketamine differed from that under pentobarbital sodium, although in both situations we observed that cortical neurons were highly synchronous.