Functional analysis of information rates conveyed by rat whisker-related trigeminal nuclei neurons.

The rat whisker system connects the tactile environment with the somatosensory thalamocortical system using only two synaptic stages. Encoding properties of the first stage, the primary afferents with somas in the trigeminal ganglion (TG), has been well studied, whereas much less is known from the second stage, the brainstem trigeminal nuclei (TN). The TN are a computational hub giving rise to parallel ascending tactile pathways and receiving feedback from many brain sites. We asked the question, whether encoding properties of TG neurons are kept by two trigeminal nuclei, the principalis (Pr5) and the spinalis interpolaris (Sp5i), respectively giving rise to two "lemniscal" and two "nonlemniscal" pathways. Single units were recorded in anesthetized rats while a single whisker was deflected on a band-limited white noise trajectory. Using information theoretic methods and spike-triggered mixture models (STM), we found that both nuclei encode the stimulus locally in time, i.e., stimulus features more than 10 ms in the past do not significantly influence spike generation. They further encode stimulus kinematics in multiple, distinct response fields, indicating encoding characteristics beyond previously described directional responses. Compared with TG, Pr5 and Sp5i gave rise to lower spike and information rates, but information rate per spike was on par with TG. Importantly, both brainstem nuclei were found to largely keep encoding properties of primary afferents, i.e. local encoding and kinematic response fields. The preservation of encoding properties in channels assumed to serve different functions seems surprising. We discuss the possibility that it might reflect specific constraints of frictional whisker contact with object surfaces.NEW & NOTEWORTHY We studied two trigeminal nuclei containing the second neuron on the tactile pathway of whisker-related tactile information in rats. We found that the subnuclei, traditionally assumed to give rise to functional tactile channels, nevertheless transfer primary afferent information with quite similar properties in terms of integration time and kinematic profile. We discuss whether such commonality may be due the requirement to adapt to physical constraints of frictional whisker contact.

Mapping the Brain-Wide Network Effects by Optogenetic Activation of the Corpus Callosum.

Optogenetically driven manipulation of circuit-specific activity enables causality studies, but its global brain-wide effect is rarely reported. Here, we applied simultaneous functional magnetic resonance imaging (fMRI) and calcium recording with optogenetic activation of the corpus callosum (CC) connecting barrel cortices (BC). Robust positive BOLD was detected in the ipsilateral BC due to antidromic activity, spreading to the ipsilateral motor cortex (MC), and posterior thalamus (PO). In the orthodromic target, positive BOLD was reliably evoked by 2 Hz light pulses, whereas 40 Hz light pulses led to reduced calcium, indicative of CC-mediated inhibition. This presumed optogenetic CC-mediated inhibition was further elucidated by pairing light pulses with whisker stimulation at varied interstimulus intervals. Whisker-induced positive BOLD and calcium signals were reduced at intervals of 50/100 ms. The calcium-amplitude-modulation-based correlation with whole-brain fMRI signal revealed that the inhibitory effects spread to contralateral BC, ipsilateral MC, and PO. This work raises the need for fMRI to elucidate the brain-wide network activation in response to optogenetic stimulation.

Propofol Affects Cortico-Hippocampal Interactions via ß3 Subunit-Containing GABAA Receptors.

BACKGROUND: General anesthetics depress neuronal activity. The depression and uncoupling of cortico-hippocampal activity may contribute to anesthetic-induced amnesia. However, the molecular targets involved in this process are not fully characterized. GABAA receptors, especially the type with ß3 subunits, represent a main molecular target of propofol. We therefore hypothesized that GABAA receptors with ß3 subunits mediate the propofol-induced disturbance of cortico-hippocampal interactions. METHODS: We used local field potential (LFP) recordings from chronically implanted cortical and hippocampal electrodes in wild-type and ß3(N265M) knock-in mice. In the ß3(N265M) mice, the action of propofol via ß3subunit containing GABAA receptors is strongly attenuated. The analytical approach contained spectral power, phase locking, and mutual information analyses in the 2-16 Hz range to investigate propofol-induced effects on cortico-hippocampal interactions. RESULTS: Propofol caused a significant increase in spectral power between 14 and 16 Hz in the cortex and hippocampus of wild-type mice. This increase was absent in the ß3(N265M) mutant. Propofol strongly decreased phase locking of 6-12 Hz oscillations in wild-type mice. This decrease was attenuated in the ß3(N265M) mutant. Finally, propofol reduced the mutual information between 6-16 Hz in wild-type mice, but only between 6 and 8 Hz in the ß3(N265M) mutant. CONCLUSIONS: GABAA receptors containing ß3 subunits contribute to frequency-specific perturbation of cortico-hippocampal interactions. This likely explains some of the amnestic actions of propofol.

Primary Tactile Thalamus Spiking Reflects Cognitive Signals.

Little is known about whether information transfer at primary sensory thalamic nuclei is modified by behavioral context. Here we studied the influence of previous decisions/rewards on current choices and preceding spike responses of ventroposterior medial thalamus (VPm; the primary sensory thalamus in the rat whisker-related tactile system). We trained head-fixed rats to detect a ramp-like deflection of one whisker interspersed within ongoing white noise stimulation. Using generative modeling of behavior, we identify two task-related variables that are predictive of actual decisions. The first reflects task engagement on a local scale ("trial history": defined as the decisions and outcomes of a small number of past trials), whereas the other captures behavioral dynamics on a global scale ("satiation": slow dynamics of the response pattern along an entire session). Although satiation brought about a slow drift from Go to NoGo decisions during the session, trial history was related to local (trial-by-trial) patterning of Go and NoGo decisions. A second model that related the same predictors first to VPm spike responses, and from there to decisions, indicated that spiking, in contrast to behavior, is sensitive to trial history but relatively insensitive to satiation. Trial history influences VPm spike rates and regularity such that a history of Go decisions would predict fewer noise-driven spikes (but more regular ones), and more ramp-driven spikes. Neuronal activity in VPm, thus, is sensitive to local behavioral history, and may play an important role in higher-order cognitive signaling.SIGNIFICANCE STATEMENT It is an important question for perceptual and brain functions to find out whether cognitive signals modulate the sensory signal stream and if so, where in the brain this happens. This study provides evidence that decision and reward history can already be reflected in the ascending sensory pathway, on the level of first-order sensory thalamus. Cognitive signals are relayed very selectively such that only local trial history (spanning a few trials) but not global history (spanning an entire session) are reflected.

Global Tactile Coding in Rat Barrel Cortex in the Absence of Local Cues.

Although whisker-related perception is based predominantly on local, near-instantaneous coding, global, intensive coding, which integrates the vibrotactile signal over time, has also been shown to play a role given appropriate behavioral conditions. Here, we study global coding in isolation by studying head-fixed rats that identified pulsatile stimuli differing in pulse frequency but not in pulse waveforms, thus abolishing perception based on local coding. We quantified time locking and spike counts as likely variables underpinning the 2 coding schemes. Both neurometric variables contained substantial stimulus information, carried even by spikes of single barrel cortex neurons. To elucidate which type of information is actually used by the rats, we systematically compared psychometric with neurometric sensitivity based on the 2 coding schemes. Neurometric performance was calculated by using a population-encoding model incorporating the properties of our recorded neuron sample. We found that sensitivity calculated from spike counts sampled over long periods (>1 s) matched the performance of rats better than the one carried by spikes time-locked to the stimulus. We conclude that spike counts are more relevant to tactile perception when instantaneous kinematic parameters are not available.

Effects of Diazepam on Low-Frequency and High-Frequency Electrocortical γ-Power Mediated by α1- and α2-GABAA Receptors.

Patterns of spontaneous electric activity in the cerebral cortex change upon administration of benzodiazepines. Here we are testing the hypothesis that the prototypical benzodiazepine, diazepam, affects spectral power density in the low (20-50 Hz) and high (50-90 Hz) γ-band by targeting GABAA receptors harboring α1- and α2-subunits. Local field potentials (LFPs) and action potentials were recorded in the barrel cortex of wild type mice and two mutant strains in which the drug exclusively acted via GABAA receptors containing either α1- (DZα1-mice) or α2-subunits (DZα2-mice). In wild type mice, diazepam enhanced low γ-power. This effect was also evident in DZα2-mice, while diazepam decreased low γ-power in DZα1-mice. Diazepam increased correlated local LFP-activity in wild type animals and DZα2- but not in DZα1-mice. In all genotypes, spectral power density in the high γ-range and multi-unit action potential activity declined upon diazepam administration. We conclude that diazepam modifies low γ-power in opposing ways via α1- and α2-GABAA receptors. The drug's boosting effect involves α2-receptors and an increase in local intra-cortical synchrony. Furthermore, it is important to make a distinction between high- and low γ-power when evaluating the effects of drugs that target GABAA receptors.

Spine loss in primary somatosensory cortex during trace eyeblink conditioning.

Classical conditioning that involves mnemonic processing, that is, a "trace" period between conditioned and unconditioned stimulus, requires awareness of the association to be formed and is considered a simple model paradigm for declarative learning. Barrel cortex, the whisker representation of primary somatosensory cortex, is required for the learning of a tactile variant of trace eyeblink conditioning (TTEBC) and undergoes distinct map plasticity during learning. To investigate the cellular mechanism underpinning TTEBC and concurrent map plasticity, we used two-photon imaging of dendritic spines in barrel cortex of awake mice while being conditioned. Monitoring layer 5 neurons' apical dendrites in layer 1, we show that one cellular expression of barrel cortex plasticity is a substantial spine count reduction of ∼15% of the dendritic spines present before learning. The number of eliminated spines and their time of elimination are tightly related to the learning success. Moreover, spine plasticity is highly specific for the principal barrel column receiving the main signals from the stimulated vibrissa. Spines located in other columns, even those directly adjacent to the principal column, are unaffected. Because layer 1 spines integrate signals from associative thalamocortical circuits, their column-specific elimination suggests that this spine plasticity may be the result of an association of top-down signals relevant for declarative learning and spatially precise ascending tactile signals.

Vibrotactile discrimination in the rat whisker system is based on neuronal coding of instantaneous kinematic cues.

Which physical parameter of vibrissa deflections is extracted by the rodent tactile system for discrimination? Particularly, it remains unclear whether perception has access to instantaneous kinematic parameters (i.e., the details of the trajectory) or relies on temporally integration of the movement trajectory such as frequency (e.g., spectral information) and intensity (e.g., mean speed). Here, we use a novel detection of change paradigm in head-fixed rats, which presents pulsatile vibrissa stimuli in seamless sequence for discrimination. This procedure ensures that processes of decision making can directly tap into sensory signals (no memory functions involved). We find that discrimination performance based on instantaneous kinematic cues far exceeds the ones provided by frequency and intensity. Neuronal modeling based on barrel cortex single units shows that small populations of sensitive neurons provide a transient signal that optimally fits the characteristic of the subject's perception. The present study is the first to show that perceptual read-out is superior in situations allowing the subject to base perception on detailed trajectory cues, that is, instantaneous kinematic variables. A possible impact of this finding on tactile systems of other species is suggested by evidence for instantaneous coding also in primates.

Rhythmic whisking area (RW) in rat primary motor cortex: an internal monitor of movement-related signals?

Vibrissae-related sensorimotor cortex controls whisking movements indirectly via modulation of lower-level sensorimotor loops and a brainstem central pattern generator (CPG). Two different whisker representations in primary motor cortex (vM1) affect whisker movements in different ways. Prolonged microstimulation in RF, a larger anterior subregion of vM1, gives rise to complex face movements and whisker retraction while the same stimulation evokes large-amplitude rhythmic whisker movement in a small caudo-medial area (RW). To characterize the motor cortex representation of explorative whisking movements, here we recorded RW units in head-fixed rats trained to contact a moving object with one whisker. RW single units were found to encode two aspects of whisker movement independently, albeit on slow time scales (hundreds of milliseconds). The first is whisker position. The second consists of speed (absolute velocity), intensity (instantaneous power), and frequency (spectral centroid). The coding for the latter three parameters was tightly correlated and realized by a continuum of RW responses-ranging from a preference of movement to a preference of rest. Information theory analysis indicated that RW spikes carry most information about position and frequency, while intensity and speed are less well represented. Further, investigating multiple and single RW units, we found a lack of phase locking, movement anticipation, and contact-related tactile responses. These findings suggest that RW neither programs detailed whisker trajectories nor initiates them. Nor does it play a role in processing object touch. Its relationship to whisking is thus indirect and may be related to movement monitoring, perhaps using feedback from the CPG.

Beyond GLMs: a generative mixture modeling approach to neural system identification.

Generalized linear models (GLMs) represent a popular choice for the probabilistic characterization of neural spike responses. While GLMs are attractive for their computational tractability, they also impose strong assumptions and thus only allow for a limited range of stimulus-response relationships to be discovered. Alternative approaches exist that make only very weak assumptions but scale poorly to high-dimensional stimulus spaces. Here we seek an approach which can gracefully interpolate between the two extremes. We extend two frequently used special cases of the GLM-a linear and a quadratic model-by assuming that the spike-triggered and non-spike-triggered distributions can be adequately represented using Gaussian mixtures. Because we derive the model from a generative perspective, its components are easy to interpret as they correspond to, for example, the spike-triggered distribution and the interspike interval distribution. The model is able to capture complex dependencies on high-dimensional stimuli with far fewer parameters than other approaches such as histogram-based methods. The added flexibility comes at the cost of a non-concave log-likelihood. We show that in practice this does not have to be an issue and the mixture-based model is able to outperform generalized linear and quadratic models.

Activity in Barrel Cortex Related to Trace Eyeblink Conditioning.

In mammals several memory systems are responsible for learning and storage of associative memory. Even apparently simple behavioral tasks, like pavlovian conditioning, have been suggested to engage, for instance, implicit and explicit memory processes. Here, we used single-whisker tactile trace eyeblink conditioning (TTEBC) to investigate learning and its neuronal bases in the mouse barrel column, the primary neocortical tactile representation of one whisker. Behavioral analysis showed that conditioned responses (CRs) are spatially highly restricted; they generalize from the principal whisker only to its direct neighbors. Within the respective neural representation, the principal column and its direct neighbors, spike activity showed a learning-related spike rate suppression starting during the late phase of conditioning stimulus (CS) presentation that was sustained throughout the stimulus-free trace period (Trace). Trial-by-trial analysis showed that learning-related activity was independent from the generation of eyelid movements within a trial, and set in around the steepest part of the learning curve. Optogenetic silencing of responses and their learning-related changes during CS and Trace epochs blocked CR acquisition but not its recall after learning. Silencing during the Trace alone, which carried major parts of the learning-related changes, had no effect. In summary, we demonstrate specific barrel column spike rate plasticity during TTEBC that can be partially decoupled from the CR, the learned eye closure, a hallmark of implicit learning. Our results, thus, point to a possible role of the barrel column in contributing to other kinds of memory as well.

Temporally Local Tactile Codes Can Be Stored in Working Memory.

Tactile exploration often involves sequential touches interspersed with stimulus-free durations (e.g., the time during which the hand moves from one textured surface to the other). Whereas it is obvious that texture-related perceptual variables, irrespective of the encoding strategy, must be stored in memory for comparison, it is rather unclear which of those variables are held in memory. There are two established variables-"intensity" and "frequency", which are "temporally global" variables because of the long stimulus integration interval required to average the signal or derive spectral components, respectively; on the other hand, a recently established third contender is the "temporally local" variable that codes for kinematic profiles of very short, suprathreshold events in the vibrotactile signal. Here, we present the first psychophysical evidence that temporally local variables can be stored in memory. To that end, we asked participants to detect changes in pulsatile indentation stimuli at their fingertips with and without a gap of 1 s between stimulus presentations. The stimuli either contained global variables alone (change of pulse rate), or a mix of local and global variables (change of pulse shape). We found, first, that humans are much better at detecting a change in stimuli when local variables are available rather than global ones alone-as evident by the fact that 21 compared to only 6 participants out of 25 yielded a valid psychophysical curve, respectively. Second, this observation persists even when there is a gap between the stimuli, implying local variables must be stored in memory. Third, an extensive array of relevant intensity definitions failed to explain participants' performance in any consistent manner, which implies that perceptual decisions were less likely to be driven by intensity coding. Taken together, our results suggest that humans perform pulsatile change detection utilizing local pulse shape, and to a lesser degree global pulse rate, and that both parameters can be stored in memory.

Local Neuronal Responses to Intracortical Microstimulation in Rats' Barrel Cortex Are Dependent on Behavioral Context.

The goal of cortical neuroprosthetics is to imprint sensory information as precisely as possible directly into cortical networks. Sensory processing, however, is dependent on the behavioral context. Therefore, a specific behavioral context may alter stimulation effects and, thus, perception. In this study, we reported how passive vs. active touch, i.e., the presence or absence of whisker movements, affects local field potential (LFP) responses to microstimulation in the barrel cortex in head-fixed behaving rats trained to move their whiskers voluntarily. The LFP responses to single-current pulses consisted of a short negative deflection corresponding to a volley of spike activity followed by a positive deflection lasting ~100 ms, corresponding to long-lasting suppression of spikes. Active touch had a characteristic effect on this response pattern. While the first phase including the negative peak remained stable, the later parts consisting of the positive peak were considerably suppressed. The stable phase varied systematically with the distance of the electrode from the stimulation site, pointing to saturation of neuronal responses to electrical stimulation in an intensity-dependent way. Our results suggest that modulatory effects known from normal sensory processing affect the response to cortical microstimulation as well. The network response to microstimulation is highly amenable to the behavioral state and must be considered for future approaches to imprint sensory signals into cortical circuits with neuroprostheses.

Integration of vibrotactile signals for whisker-related perception in rats is governed by short time constants: comparison of neurometric and psychometric detection performance.

Rats explore environments by sweeping their whiskers across objects and surfaces. Both sensor movement and repetitive sweeping typical for this behavior require that vibrotactile signals are integrated over time. While temporal integration properties of neurons along the whisker somatosensory pathway have been studied extensively, the consequences for behavior are unknown. Here, we investigate the ability of head-fixed rats to integrate information over time for the detection of near-threshold pulsatile deflection sequences applied to a single whisker. Psychometric detection performance was assessed with whisker stimuli composed of different numbers of pulses (1-31) delivered at varying frequencies (10, 20, 100 Hz). Detection performance indeed improved with increasing number and frequency of pulses, albeit this improvement was much lower than predicted by probabilistic combination, suggesting highly sublinear integration of pulses. This behavioral observation was reflected in the firing properties of concomitantly recorded barrel cortex neurons, which showed substantial response adaptation to repetitive whisker deflection. To estimate the integration time with which barrel cortex neuronal activity must be read out to match behavior, we constructed a model monitoring spiking activity of simulated neuronal pools, where spike trains were channeled through a leaky integrator with exponential decay. Detection was accomplished by simple threshold crossings. This simple model gave an excellent match of neurometric and psychometric data at surprisingly small time constants tau of 5-8 ms, thus limiting integration largely to <25 ms. This result carries important implications regarding sensory processing for whisker-mediated perception.

Mislocalization of near-threshold tactile stimuli in humans: a central or peripheral phenomenon?

Principles of brain function can be disclosed by studying their limits during performance. Tactile stimuli with near-threshold intensities have been used to assess features of somatosensory processing. When stimulating fingers of one hand using near-threshold intensities, localization errors are observed that deviate significantly from responses obtained by guessing - incorrectly located stimuli are attributed more often to fingers neighbouring the stimulated one than to more distant fingers. Two hypotheses to explain the findings are proposed. The 'central hypothesis' posits that the degree of overlap of cortical tactile representations depends on stimulus intensity, with representations less separated for near-threshold stimuli than for suprathreshold stimuli. The 'peripheral hypothesis' assumes that systematic mislocalizations are due to activation of different sets of skin receptors with specific thresholds. The present experiments were designed to decide between the two hypotheses. Taking advantage of the frequency tuning of somatosensory receptors, their contribution to systematic misclocalizations was studied. In the first experiment, mislocalization profiles were investigated using vibratory stimuli with frequencies of 10, 20 and 100 Hz. Unambiguous mislocalization effects were only obtained for the 10-Hz stimulation, precluding the involvement of Pacinian corpuscles in systematic mislocalization. In the second experiment, Pacinian corpuscles were functionally eliminated by applying a constant 100-Hz vibratory masking stimulus together with near-threshold pulses. Despite masking, systematic mislocation patterns were observed rendering the involvement of Pacinian corpuscles unlikely. The results of both experiments are in favor of the 'central hypothesis' assuming that the extent of overlap in somatosensory representations is modulated by stimulus intensity.

Humans Use a Temporally Local Code for Vibrotactile Perception.

Sensory environments are commonly characterized by specific physical features, which sensory systems might exploit using dedicated processing mechanisms. In the tactile sense, one such characteristic feature is frictional movement, which gives rise to short-lasting (<10 ms), information-carrying integument vibrations. Rather than generic integrative encoding (i.e., averaging or spectral analysis capturing the "intensity" and "best frequency"), the tactile system might benefit from, what we call a "temporally local" coding scheme that instantaneously detects and analyzes shapes of these short-lasting features. Here, by employing analytic psychophysical measurements, we tested whether the prerequisite of temporally local coding exists in the human tactile system. We employed pulsatile skin indentations at the fingertip that allowed us to trade manipulation of local pulse shape against changes in global intensity and frequency, achieved by adding pulses of the same shape. We found that manipulation of local pulse shape has strong effects on psychophysical performance, arguing for the notion that humans implement a temporally local coding scheme for perceptual decisions. As we found distinct differences in performance using different kinematic layouts of pulses, we inquired whether temporally local coding is tuned to a unique kinematic variable. This was not the case, since we observed different preferred kinematic variables in different ranges of pulse shapes. Using an established encoding model for primary afferences and indentation stimuli, we were able to demonstrate that the found kinematic preferences in human performance, may well be explained by the response characteristics of Pacinian corpuscles (PCs), a class of human tactile primary afferents.

Adaptive Whisking in Mice.

Rodents generate rhythmic whisking movements to explore their environment. Whisking trajectories, for one, appear as a fixed pattern of whisk cycles at 5-10 Hz driven by a brain stem central pattern generator. In contrast, whisking behavior is thought to be versatile and adaptable to behavioral goals. To begin to systematically investigate such behavioral adaptation, we established a whisking task, in which mice altered the trajectories of whisking in a goal-oriented fashion to gain rewards. Mice were trained to set the whisker to a defined starting position and generate a protraction movement across a virtual target (no touch-related tactile feedback). By ramping up target distance based on reward history, we observed that mice are able to generate highly specific whisking patterns suited to keep reward probability constant. On a sensorimotor level, the behavioral adaptation was realized by adjusting whisker kinematics: more distant locations were targeted using higher velocities (i.e., pointing to longer force generation), rather than by generating higher acceleration (i.e., pointing to stronger forces). We tested the suitability of the paradigm of tracking subtle alteration in whisking motor commands using small lesions in the rhythmic whisking subfield (RW) of the whisking-related primary motor cortex. Small contralateral RW lesions generated the deterioration of whisking kinematics with a latency of 12 days post-lesion, a change that was readily discriminated from changes in the behavioral adaptation by the paradigm.

Conveyance of texture signals along a rat whisker.

Neuronal activities underlying a percept are constrained by the physics of sensory signals. In the tactile sense such constraints are frictional stick-slip events, occurring, amongst other vibrotactile features, when tactile sensors are in contact with objects. We reveal new biomechanical phenomena about the transmission of these microNewton forces at the tip of a rat's whisker, where they occur, to the base where they engage primary afferents. Using high resolution videography and accurate measurement of axial and normal forces at the follicle, we show that the conical and curved rat whisker acts as a sign-converting amplification filter for moment to robustly engage primary afferents. Furthermore, we present a model based on geometrically nonlinear Cosserat rod theory and a friction model that recreates the observed whole-beam whisker dynamics. The model quantifies the relation between kinematics (positions and velocities) and dynamic variables (forces and moments). Thus, only videographic assessment of acceleration is required to estimate forces and moments measured by the primary afferents. Our study highlights how sensory systems deal with complex physical constraints of perceptual targets and sensors.

Cross-approximate entropy of cortical local field potentials quantifies effects of anesthesia--a pilot study in rats.

BACKGROUND: Anesthetics dose-dependently shift electroencephalographic (EEG) activity towards high-amplitude, slow rhythms, indicative of a synchronization of neuronal activity in thalamocortical networks. Additionally, they uncouple brain areas in higher (gamma) frequency ranges possibly underlying conscious perception. It is currently thought that both effects may impair brain function by impeding proper information exchange between cortical areas. But what happens at the local network level? Local networks with strong excitatory interconnections may be more resilient towards global changes in brain rhythms, but depend heavily on locally projecting, inhibitory interneurons. As anesthetics bias cortical networks towards inhibition, we hypothesized that they may cause excessive synchrony and compromise information processing already on a small spatial scale. Using a recently introduced measure of signal independence, cross-approximate entropy (XApEn), we investigated to what degree anesthetics synchronized local cortical network activity. We recorded local field potentials (LFP) from the somatosensory cortex of three rats chronically implanted with multielectrode arrays and compared activity patterns under control (awake state) with those at increasing concentrations of isoflurane, enflurane and halothane. RESULTS: Cortical LFP signals were more synchronous, as expressed by XApEn, in the presence of anesthetics. Specifically, XApEn was a monotonously declining function of anesthetic concentration. Isoflurane and enflurane were indistinguishable; at a concentration of 1 MAC (the minimum alveolar concentration required to suppress movement in response to noxious stimuli in 50% of subjects) both volatile agents reduced XApEn by about 70%, whereas halothane was less potent (50% reduction). CONCLUSIONS: The results suggest that anesthetics strongly diminish the independence of operation of local cortical neuronal populations, and that the quantification of these effects in terms of XApEn has a similar discriminatory power as changes of spontaneous action potential rates. Thus, XApEn of field potentials recorded from local cortical networks provides valuable information on the anesthetic state of the brain.