Cortical Firing Rates Research Articles

Contributed Session III: Identifying Specific Neural Substrates for Bayesian-like Computations in Binocular Vision and Multisensory Processing.

Bayesian thinking is influential in vision but the grounding of Bayesian computation in wetware is poorly understood. Bayesian reliability (inverse variance) weighting of inputs is predicted by Maximum Likelihood Estimation Theory and has some psychophysical support, but evidence for neural reliability weighting is sparse and neural modeling of reliability weighting is tricky. However, reliability averaging is just one possible perceptual weighted average. An alternative - nonlinear magnitude-weighted averaging - was suggested by Schrodinger in 1926 to account for suprathreshold binocular perception and is available to repurpose for other sensory cue combinations. We identified macaque suppressive binocular neurons that implement nonlinear magnitude-weighted averaging and approximate Bayesian averaging, without suffering the computational difficulties that Bayesian averaging implies. We then applied the binocular modeling to suppressive multisensory (visual-tactile, audio-tactile, and audio-visual) neurons. Although magnitude-weighting is a better fit than reliability-weighted averaging for cortical firing rates (in all four cases and in three different species), nonlinear magnitude-weighted averaging is well correlated with reliability averaging. Magnitude-weighted averaging could serve as a surrogate for Bayesian calculations; mildly suppressive binocular and multisensory bimodal neurons could be neural correlates of Bayesian-like computation in the brain.

Laminar mechanisms of saccadic suppression in primate visual cortex

Saccadic eye movements are known to cause saccadic suppression, a temporary reduction in visual sensitivity and visual cortical firing rates. While saccadic suppression has been well characterized at the level of perception and single neurons, relatively little is known about the visual cortical networks governing this phenomenon. Here we examine the effects of saccadic suppression on distinct neural subpopulations within visual area V4. We find subpopulation-specific differences in the magnitude and timing of peri-saccadic modulation. Input-layer neurons show changes in firing rate and inter-neuronal correlations prior to saccade onset, and putative inhibitory interneurons in the input layer elevate their firing rate during saccades. A computational model of this circuit recapitulates our empirical observations and demonstrates that an input-layer-targeting pathway can initiate saccadic suppression by enhancing local inhibitory activity. Collectively, our results provide a mechanistic understanding of how eye movement signaling interacts with cortical circuitry to enforce visual stability.

Distinct signatures of loss of consciousness in focal impaired awareness versus tonic-clonic seizures.

Loss of consciousness is a hallmark of many epileptic seizures and carries risks of serious injury and sudden death. While cortical sleep-like activities accompany loss of consciousness during focal impaired awareness seizures, the mechanisms of loss of consciousness during focal to bilateral tonic-clonic seizures remain unclear. Quantifying differences in markers of cortical activation and ictal recruitment between focal impaired awareness and focal to bilateral tonic-clonic seizures may also help us to understand their different consequences for clinical outcomes and to optimize neuromodulation therapies. We quantified clinical signs of loss of consciousness and intracranial EEG activity during 129 focal impaired awareness and 50 focal to bilateral tonic-clonic from 41 patients. We characterized intracranial EEG changes both in the seizure onset zone and in areas remote from the seizure onset zone with a total of 3386 electrodes distributed across brain areas. First, we compared the dynamics of intracranial EEG sleep-like activities: slow-wave activity (1-4 Hz) and beta/delta ratio (a validated marker of cortical activation) during focal impaired awareness versus focal to bilateral tonic-clonic. Second, we quantified differences between focal to bilateral tonic-clonic and focal impaired awareness for a marker validated to detect ictal cross-frequency coupling: phase-locked high gamma (high-gamma phased-locked to low frequencies) and a marker of ictal recruitment: the epileptogenicity index. Third, we assessed changes in intracranial EEG activity preceding and accompanying behavioural generalization onset and their correlation with electromyogram channels. In addition, we analysed human cortical multi-unit activity recorded with Utah arrays during three focal to bilateral tonic-clonic seizures. Compared to focal impaired awareness, focal to bilateral tonic-clonic seizures were characterized by deeper loss of consciousness, even before generalization occurred. Unlike during focal impaired awareness, early loss of consciousness before generalization was accompanied by paradoxical decreases in slow-wave activity and by increases in high-gamma activity in parieto-occipital and temporal cortex. After generalization, when all patients displayed loss of consciousness, stronger increases in slow-wave activity were observed in parieto-occipital cortex, while more widespread increases in cortical activation (beta/delta ratio), ictal cross-frequency coupling (phase-locked high gamma) and ictal recruitment (epileptogenicity index). Behavioural generalization coincided with a whole-brain increase in high-gamma activity, which was especially synchronous in deep sources and could not be explained by EMG. Similarly, multi-unit activity analysis of focal to bilateral tonic-clonic revealed sustained increases in cortical firing rates during and after generalization onset in areas remote from the seizure onset zone. Overall, these results indicate that unlike during focal impaired awareness, the neural signatures of loss of consciousness during focal to bilateral tonic-clonic consist of paradoxical increases in cortical activation and neuronal firing found most consistently in posterior brain regions. These findings suggest differences in the mechanisms of ictal loss of consciousness between focal impaired awareness and focal to bilateral tonic-clonic and may account for the more negative prognostic consequences of focal to bilateral tonic-clonic.

Subsampled Directed-Percolation Models Explain Scaling Relations Experimentally Observed in the Brain.

Recent experimental results on spike avalanches measured in the urethane-anesthetized rat cortex have revealed scaling relations that indicate a phase transition at a specific level of cortical firing rate variability. The scaling relations point to critical exponents whose values differ from those of a branching process, which has been the canonical model employed to understand brain criticality. This suggested that a different model, with a different phase transition, might be required to explain the data. Here we show that this is not necessarily the case. By employing two different models belonging to the same universality class as the branching process (mean-field directed percolation) and treating the simulation data exactly like experimental data, we reproduce most of the experimental results. We find that subsampling the model and adjusting the time bin used to define avalanches (as done with experimental data) are sufficient ingredients to change the apparent exponents of the critical point. Moreover, experimental data is only reproduced within a very narrow range in parameter space around the phase transition.

Differential effects of the mode of touch, active and passive, on experience-driven plasticity in the S1 cutaneous digit representation of adult macaque monkeys.

This study compared the receptive field (RF) properties and firing rates of neurons in the cutaneous hand representation of primary somatosensory cortex (areas 3b, 1, and 2) of 9 awake, adult macaques that were intensively trained in a texture discrimination task using active touch (fingertips scanned over the surfaces using a single voluntary movement), passive touch (surfaces displaced under the immobile fingertips), or both active and passive touch. Two control monkeys received passive exposure to the same textures in the context of a visual discrimination task. Training and recording extended over 1-2 yr per animal. All neurons had a cutaneous receptive field (RF) that included the tips of the stimulated digits (D3 and/or D4). In area 3b, RFs were largest in monkeys trained with active touch, smallest in those trained with passive touch, and intermediate in those trained with both; i.e., the mode of touch differentially modified the cortical representation of the stimulated fingers. The same trends were seen in areas 1 and 2, but the changes were not significant, possibly because a second experience-driven influence was seen in areas 1 and 2, but not in area 3b: smaller RFs with passive exposure to irrelevant tactile inputs compared with recordings from one naive hemisphere. We suggest that added feedback during active touch and higher cortical firing rates were responsible for the larger RFs with behavioral training; this influence was tempered by periods of more restricted sensory feedback during passive touch training in the active + passive monkeys.NEW & NOTEWORTHY We studied experience-dependent sensory cortical plasticity in relation to tactile discrimination of texture using active and/or passive touch. We showed that neuronal receptive fields in primary somatosensory cortex, especially area 3b, are largest in monkeys trained with active touch, smallest in those trained with passive touch, and intermediate in those trained using both modes of touch. Prolonged, irrelevant tactile input had the opposite influence in areas 1 and 2, favoring smaller receptive fields.

Rapid and active stabilization of visual cortical firing rates across light–dark transitions

The dynamics of neuronal firing during natural vision are poorly understood. Surprisingly, mean firing rates of neurons in primary visual cortex (V1) of freely behaving rodents are similar during prolonged periods of light and darkness, but it is unknown whether this reflects a slow adaptation to changes in natural visual input or insensitivity to rapid changes in visual drive. Here, we use chronic electrophysiology in freely behaving rats to follow individual V1 neurons across many dark-light (D-L) and light-dark (L-D) transitions. We show that, even on rapid timescales (1 s to 10 min), neuronal activity was only weakly modulated by transitions that coincided with the expected 12-/12-h L-D cycle. In contrast, a larger subset of V1 neurons consistently responded to unexpected L-D and D-L transitions, and disruption of the regular L-D cycle with 60 h of complete darkness induced a robust increase in V1 firing on reintroduction of visual input. Thus, V1 neurons fire at similar rates in the presence or absence of natural stimuli, and significant changes in activity arise only transiently in response to unexpected changes in the visual environment. Furthermore, although mean rates were similar in light and darkness, pairwise correlations were significantly stronger during natural vision, suggesting that information about natural scenes in V1 may be more strongly reflected in correlations than individual firing rates. Together, our findings show that V1 firing rates are rapidly and actively stabilized during expected changes in visual input and are remarkably stable at both short and long timescales.

Resting-State Neural Firing Rate Is Linked to Cardiac-Cycle Duration in the Human Cingulate and Parahippocampal Cortices.

Stimulation and functional imaging studies have revealed the existence of a large network of cortical regions involved in the regulation of heart rate. However, very little is known about the link between cortical neural firing and cardiac-cycle duration (CCD). Here, we analyze single-unit and multiunit data obtained in humans at rest, and show that firing rate covaries with CCD in 16.7% of the sample (25 of 150). The link between firing rate and CCD was most prevalent in the anterior medial temporal lobe (entorhinal and perirhinal cortices, anterior hippocampus, and amygdala), where 36% (18 of 50) of the units show the effect, and to a lesser extent in the mid-to-anterior cingulate cortex (11.1%, 5 of 45). The variance in firing rate explained by CCD ranged from 0.5 to 11%. Several lines of analysis indicate that neural firing influences CCD, rather than the other way around, and that neural firing affects CCD through vagally mediated mechanisms in most cases. These results show that part of the spontaneous fluctuations in firing rate can be attributed to the cortical control of the cardiac cycle. The fine tuning of the regulation of CCD represents a novel physiological factor accounting for spontaneous variance in firing rate. It remains to be determined whether the “noise” introduced in firing rate by the regulation of CCD is detrimental or beneficial to the cognitive information processing carried out in the parahippocampal and cingulate regions.SIGNIFICANCE STATEMENT Fluctuations in heart rate are known to be under the control of cortical structures, but spontaneous fluctuations in cortical firing rate, or “noise,” have seldom been related to heart rate. Here, we analyze unit activity in humans at rest and show that spontaneous fluctuations in neural firing in the medial temporal lobe, as well as in the mid-to-anterior cingulate cortex, influence heart rate. This phenomenon was particularly pronounced in the entorhinal and perirhinal cortices, where it could be observed in one of three neurons. Our results show that part of spontaneous firing rate variability in regions best known for their cognitive role in spatial navigation and memory corresponds to precise physiological regulations.

S115 Sleep slow wave oscillation and homeostasis

Sleep electroencephalogram (EEG) slow waves (0.5–4 Hz) are considered the major hallmarks and functional constituents of non-rapid eye movement (NREM) sleep. Since their first description by Alfred Lee Loomis in the 1930s these oscillatory electrophysiological phenomena were gradually becoming one of the major focuses of sleep scientists. Although they were first considered as pure signs of cerebral inactivity, empirical findings suggested their involvement in the maintenance of a homeostasis between wake-related cerebral activity and sleep-related rest, restauration of wake-related wear and tear (including detoxification, tissue restoration and immunological functions), maintaining synaptic homeostasis (reducing synaptic strengths and cortical firing rate) and consolidation of memory traces (hippocamapo-neocortical replay). The precise homeostatic regulation of sleep slow wave activity is one of the best characterized aspects of sleep. Spectral power, wave amplitude and occurrence, as well as frequency and slope are the sleep slow wave features which are homeostatically regulated, mainly reflecting local plastic processes. The dichotomy of the cortically generated slow oscillation.

Multiple shared mechanisms for homeostatic plasticity in rodent somatosensory and visual cortex

We compare the circuit and cellular mechanisms for homeostatic plasticity that have been discovered in rodent somatosensory (S1) and visual (V1) cortex. Both areas use similar mechanisms to restore mean firing rate after sensory deprivation. Two time scales of homeostasis are evident, with distinct mechanisms. Slow homeostasis occurs over several days, and is mediated by homeostatic synaptic scaling in excitatory networks and, in some cases, homeostatic adjustment of pyramidal cell intrinsic excitability. Fast homeostasis occurs within less than 1 day, and is mediated by rapid disinhibition, implemented by activity-dependent plasticity in parvalbumin interneuron circuits. These processes interact with Hebbian synaptic plasticity to maintain cortical firing rates during learned adjustments in sensory representations.This article is part of the themed issue 'Integrating Hebbian and homeostatic plasticity'.

Operant conditioning of neural activity in freely behaving monkeys with intracranial reinforcement.

Operant conditioning of neural activity has typically been performed under controlled behavioral conditions using food reinforcement. This has limited the duration and behavioral context for neural conditioning. To reward cell activity in unconstrained primates, we sought sites in nucleus accumbens (NAc) whose stimulation reinforced operant responding. In three monkeys, NAc stimulation sustained performance of a manual target-tracking task, with response rates that increased monotonically with increasing NAc stimulation. We recorded activity of single motor cortex neurons and documented their modulation with wrist force. We conditioned increased firing rates with the monkey seated in the training booth and during free behavior in the cage using an autonomous head-fixed recording and stimulating system. Spikes occurring above baseline rates triggered single or multiple electrical pulses to the reinforcement site. Such rate-contingent, unit-triggered stimulation was made available for periods of 1-3 min separated by 3-10 min time-out periods. Feedback was presented as event-triggered clicks both in-cage and in-booth, and visual cues were provided in many in-booth sessions. In-booth conditioning produced increases in single neuron firing probability with intracranial reinforcement in 48 of 58 cells. Reinforced cell activity could rise more than five times that of non-reinforced activity. In-cage conditioning produced significant increases in 21 of 33 sessions. In-cage rate changes peaked later and lasted longer than in-booth changes, but were often comparatively smaller, between 13 and 18% above non-reinforced activity. Thus intracranial stimulation reinforced volitional increases in cortical firing rates during both free behavior and a controlled environment, although changes in the latter were more robust.NEW & NOTEWORTHY Closed-loop brain-computer interfaces (BCI) were used to operantly condition increases in muscle and neural activity in monkeys by delivering activity-dependent stimuli to an intracranial reinforcement site (nucleus accumbens). We conditioned increased firing rates with the monkeys seated in a training booth and also, for the first time, during free behavior in a cage using an autonomous head-fixed BCI.

Stereotypic wheel running decreases cortical activity in mice.

Prolonged wakefulness is thought to gradually increase ‘sleep need' and influence subsequent sleep duration and intensity, but the role of specific waking behaviours remains unclear. Here we report the effect of voluntary wheel running during wakefulness on neuronal activity in the motor and somatosensory cortex in mice. We find that stereotypic wheel running is associated with a substantial reduction in firing rates among a large subpopulation of cortical neurons, especially at high speeds. Wheel running also has longer-term effects on spiking activity across periods of wakefulness. Specifically, cortical firing rates are significantly higher towards the end of a spontaneous prolonged waking period. However, this increase is abolished when wakefulness is dominated by running wheel activity. These findings indicate that wake-related changes in firing rates are determined not only by wake duration, but also by specific waking behaviours.

Spiking network modeling of neuronal dynamics in individual rats

Many researchers base their neuronal models on experimental data, but few systematically calibrate to it, and even fewer use unpooled data from multiple subjects. Some (partial) exceptions are [1], where one model parameter was calibrated to data pooled across four macaques; and [2], where five model parameters were calibrated to unpooled data from 292 humans. To our knowledge, no one has previously calibrated spiking network models to individual subjects - likely because a single model iteration typically takes considerable computational time, compounded by the formidable number of iterations required to perform optimizations on a statistically meaningful number of subjects. In this study, we calibrate and validate a mesoscopic spiking network model against data from individual rats, then use these fits to infer differences in the rats' physiologies. We recorded data from microelectrode arrays implanted in the somatosensory cortices of nine male rats, each of whom received touch stimuli to his left forepaw. The spiking network models consisted of 20,000 Izhikevich neurons, representing a 2x2 mm patch of cortex sampled at approximately 10% true cell density, with cell types (15 across six layers) and connectivities based on empirical data. We calibrated key model parameters (including connection probability and weight, tonic background activity, and the ratio of thalamic to cortical input) to experimental data (including average firing rates and coefficients of variation) using a nonlinear optimization algorithm [3]. The calibrations were validated using the exponents of the local field potential (LFP) power spectra from 5-50 Hz, which were not used for calibration. Changes in the information processing properties of the (simulated) networks were then quantified via interlaminar Granger causality. Experimentally, we found large differences between subjects. Cortical firing rates varied from 3.8 Hz to 19.6 Hz (median 11.9 Hz); coefficients of variation, 0.4 to 1.2 (median 0.9); and peristimulus time histogram peak amplitudes, 48 Hz to 73 Hz (median 62 Hz). Inter-subject differences were significantly greater than intra-subject differences across both sessions and electrodes. The calibrated models reproduced experimental data with an average mismatch of 16%, compared to 30% when uncalibrated. Experimentally, the LFP power spectra exponents varied from -1.4 to -2.7 (median -2.2). While the models had uniformly steeper exponents (range -2.8 to -3.6), calibration reduced mismatch in eight of the nine subjects. Inter-subject differences could be largely accounted for by differences in average synaptic connection probability (which varied by a mean of 24% between subjects, compared to <8% for other fitted parameters). Parameter differences produced changes in how these networks process information - for example, there were significant and complex differences in the patterns of interlaminar information flow between subjects, including reversals in the dominant direction of information flow for some layer pairs. In summary, we found that (1) significant differences exist between individual subjects, (2) these differences can be captured by calibrating spiking network models to data from each individual, and (3) modeling suggests that these differences affect how individuals process information across cortical layers.

Practical Applications of Dynamic Choice and Optimal Annuitization

<h3>Abstract</h3> Loss of consciousness (LOC) is a hallmark of many epileptic seizures and carries risks of serious injury and sudden death. While cortical sleep-like activities accompany LOC during focal impaired awareness (FIA) seizures, the mechanisms of LOC during focal to bilateral tonic-clonic (FBTC) seizures remain unclear. Quantifying differences in markers of cortical activation and ictal recruitment between FIA and FBTC seizures may also help to understand their different consequences for clinical outcomes and to optimize neuromodulation therapies. We quantified clinical signs of LOC and intracranial EEG (iEEG) activity during 129 FIA and 50 FBTC from 41 patients. We characterized iEEG changes both in the seizure onset zone (SOZ) and in areas remote from SOZ with a total of 3386 electrodes distributed across brain areas. First, we compared the dynamics of iEEG sleep-like activities: slow-wave activity (SWA; 1-4 Hz) and beta/delta ratio (B/D; a validated marker of cortical activation) during FIA vs. FBTC. Second, we quantified differences between FBTC and FIA for a marker validated to detect ictal cross-frequency coupling: phase-locked high-gamma (PLHG; high gamma phased locked to low frequencies) and a marker of ictal recruitment: the epileptogenicity index (i.e. the number of channels crossing an energy ratio threshold for high vs. low frequency power). Third, we assessed changes in iEEG activity preceding and accompanying behavioral generalization onset and their correlation with electromyogram (EMG) channels. In addition, we analyzed human cortical multi-unit activity recorded with Utah arrays during three FBTC. Compared to FIA, FBTC seizures were characterized by deeper LOC and by stronger increases in SWA in parieto-occipital cortex. FBTC also displayed more widespread increases in cortical activation (B/D), ictal cross-frequency coupling (PLHG) and ictal recruitment (epileptogenicity index). Even before generalization, FBTC displayed deeper LOC; this early LOC was accompanied by a paradoxical increase in B/D in fronto-parietal cortex. Behavioral generalization coincided with complete loss of responsiveness and a subsequent increase in high-gamma in the whole brain, which was especially synchronous in deep sources and could not be explained by EMG. Similarly, multi-unit activity analysis of FBTC revealed sustained increases in cortical firing rates during and after generalization onset in areas remote from the SOZ. Unlike during FIA, LOC during FBTC is characterized by a paradoxical increase in cortical activation and neuronal firing. These findings suggest differences in the mechanisms of ictal LOC between FIA and FBTC and may account for the more negative prognostic consequences of FBTC.

Neuromodulators produce distinct activated states in neocortex.

Neocortical population activity varies between deactivated and activated states marked by the presence and absence of slow oscillations, respectively. Neocortex activation occurs during waking and vigilance and is readily induced in anesthetized animals by stimulating the brainstem reticular formation, basal forebrain, or thalamus. Neuromodulators are thought to be responsible for these changes in cortical activity, but their selective cortical effects (i.e., without actions in other brain areas) on neocortical population activity in vivo are not well defined. We found that selective cholinergic and noradrenergic stimulation of the barrel cortex produces well differentiated activated states in rats. Cholinergic cortical stimulation activates the cortex by abolishing synchronous slow oscillations and shifting firing to a tonic mode, which increases in rate at high doses. This shift causes the sensory thalamus itself to become activated. In contrast, noradrenergic cortical stimulation activates the cortex by abolishing synchronous slow oscillations but suppresses overall cortical firing rate, which deactivates the thalamus. Cortical activation produced by either of these neuromodulators leads to suppressed sensory responses and more focused receptive fields. High-frequency sensory stimuli are best relayed to barrel cortex during cortical cholinergic activation because this also activates the thalamus. Cortical neuromodulation sets different cortical and thalamic states that may serve to control sensory information processing according to behavioral contingencies.

Effect of Early and Late Rehabilitation Onset in a Chronic Rat Model of Ischemic Stroke— Assessment of Motor Cortex Signaling and Gait Functionality Over Time

The aim of the present study was to investigate the effects of ischemic stroke and onset of subsequent rehabilitation of gait function in rats. Nine male Sprague-Dawley rats were instrumented with a 16-channel intracortical (IC) electrode array. An ischemic stroke was induced within the hindlimb area of the left motor cortex. The rehabilitation consisted of a repetitive training paradigm over 28 days, initiated on day one ("Early-onset", 5 rats) and on day seven, ("Late-onset", 4 rats). Data were obtained from IC microstimulation tests, treadmill walking tests, and beam walking tests. Results revealed an expansion of the hindlimb representation within the motor cortex area and an increased amount of cortical firing rate modulation for the "Early-onset" group but not for the "Late-onset" group. Kinematic data revealed a significant change for both intervention groups. However, this difference was larger for the "Early-onset" group. Results from the beam walking test showed functional performance deficits following stroke which returned to pre-stroke level after the rehabilitative training. The results from the present study indicate the existence of a critical time period following stroke where onset of rehabilitative training may be more effective and related to a higher degree of true recovery.

Task-related “cortical” bursting depends critically on basal ganglia input and is linked to vocal plasticity

Basal ganglia-thalamocortical circuits are critical for motor control and motor learning. Classically, basal ganglia nuclei are thought to regulate motor behavior by increasing or decreasing cortical firing rates, and basal ganglia diseases are assumed to reflect abnormal overall activity levels. More recent studies suggest instead that motor disorders derive from abnormal firing patterns, and have led to the hypothesis that surgical treatments, such as pallidotomy, act primarily by eliminating pathological firing patterns. Surprisingly little is known, however, about how the basal ganglia normally influence task-related cortical activity to regulate motor behavior, and how lesions of the basal ganglia influence cortical firing properties. Here, we investigated these questions in a songbird circuit that has striking homologies to mammalian basal ganglia-thalamocortical circuits but is specialized for singing. The "cortical" outflow nucleus of this circuit is required for song plasticity and normally exhibits increased firing during singing and song-locked burst firing. We found that lesions of the striato-pallidal nucleus in this circuit prevented hearing-dependent song changes. These basal ganglia lesions also stripped the cortical outflow neurons of their patterned burst firing during singing, without changing their spontaneous or singing-related firing rates. Taken together, these results suggest that the basal ganglia are essential not for normal cortical firing rates but for driving task-specific cortical firing patterns, including bursts. Moreover, such patterned bursting appears critical for motor plasticity. Our findings thus provide support for therapies that aim to treat basal ganglia movement disorders by normalizing firing patterns.

Extracellular Levels of Lactate, but Not Oxygen, Reflect Sleep Homeostasis in the Rat Cerebral Cortex

It is well established that brain metabolism is higher during wake and rapid eye movement (REM) sleep than in nonrapid eye movement (NREM) sleep. Most of the brain's energy is used to maintain neuronal firing and glutamatergic transmission. Recent evidence shows that cortical firing rates, extracellular glutamate levels, and markers of excitatory synaptic strength increase with time spent awake and decline throughout NREM sleep. These data imply that the metabolic cost of each behavioral state is not fixed but may reflect sleep-wake history, a possibility that is investigated in the current report. Chronic (4d) electroencephalographic (EEG) recordings in the rat cerebral cortex were coupled with fixed-potential amperometry to monitor the extracellular concentration of oxygen ([oxy]) and lactate ([lac]) on a second-by-second basis across the spontaneous sleep-wake cycle and in response to sleep deprivation. Basic sleep research laboratory. Wistar Kyoto (WKY) adult male rats. N/A. Within 30-60 sec [lac] and [oxy] progressively increased during wake and REM sleep and declined during NREM sleep (n = 10 rats/metabolite), but with several differences. [Oxy], but not [lac], increased more during wake with high motor activity and/or elevated EEG high-frequency power. Meanwhile, only the NREM decline of [lac] reflected sleep pressure as measured by slow-wave activity, mirroring previous results for cortical glutamate. The observed state-dependent changes in cortical [lac] and [oxy] are consistent with higher brain metabolism during waking and REM sleep in comparison with NREM sleep. Moreover, these data suggest that glycolytic activity, most likely through its link with glutamatergic transmission, reflects sleep homeostasis.

Modeling the Gabaergic Action of Etomidate on the Thalamocortical System

We have used a computational model of the thalamocortical system to investigate the effects of a GABAergic anesthetic (etomidate) on cerebral cortical and thalamic neuronal function. We examined the effects of phasic and tonic inhibition, as well as the relative importance of anesthetic action in the thalamus and cortex. The amount of phasic GABAergic inhibition was adjusted in the model to simulate etomidate concentrations of between 0.25 and 2 microM, with the concentration range producing unconsciousness assumed to be between 0.25 and 0.5 microM. In addition, we modeled tonic inhibition separately, and then phasic and tonic inhibition together. We also introduced phasic and tonic inhibition into the cerebral cortex and thalamus separately to determine the relative importance of each of these structures to anesthetic-induced depression of the thalamocortical system. Phasic inhibition decreased cortical neuronal firing by 11%-18% in the 0.25-0.5 microM range and by 38% at 2 microM. Tonic inhibition produced similar depression (11%-21%) in the 0.25-0.5 microM range but 65% depression at 2 microM; phasic and tonic inhibition combined produced the most inhibition (76% depression at 2 microM). When the thalamus and cortex were separately subjected to phasic and tonic inhibition, cortical firing rates decreased less compared to when both structures were targeted. In the 0.25-0.5 microM range, cortical firing rate was minimally affected when etomidate action was simulated in the thalamus only. This computational model of the thalamocortical system indicated that tonic GABAergic inhibition seems to be more important than phasic GABAergic inhibition (especially at larger etomidate concentrations), although both combined had the most effect on cerebral cortical firing rates. Furthermore, etomidate action in the thalamus, by itself, does not likely explain etomidate-induced unconsciousness.

Correlated physiological and perceptual effects of noise in a tactile stimulus

Event Abstract Back to Event Correlated physiological and perceptual effects of noise in a tactile stimulus Comparing neuronal firing parameters with the perceptual report for the same stimuli can be a powerful strategy for uncovering the brain's encoding and decoding mechanisms. The work reported here utilizes that strategy, but with the twist that the neuronal activity is recorded from the whisker-region of rat cortex (barrel cortex) while the perceptual report comes from human subjects. The stimuli in both cases are trains of skin deflections. If the predictions made from the barrel cortex data set are borne out in tests of human tactile perception, we can propose general coding principles that extend across species. We first investigated the responses of neurons in anesthetized rat barrel cortex to trains of whisker deflection, where each train had a periodic temporal structure but was characterized by either a constant-amplitude across all deflections or else variable amplitude (''amplitude noise''). Stimulus trains containing amplitude noise were matched with constant-amplitude trains for mean amplitude but included deflections smaller and larger than the mean. Cortical extracellular responses '' collected from the middle layers '' were equivalent for constant and noisy stimulus trains with frequencies up to 10 Hz. Above 10 Hz, amplitude noise led to a larger response magnitude as well as more prominent firing synchrony. The effects of amplitude noise are thus remarkably similar to those reported earlier for temporal noise: stimulus trains with an irregular sequence of interdeflection intervals evoke a larger and more synchronous cortical response than do frequency-matched periodic stimulus trains (Lak et al., Cerebral Cortex, 2008). The Romo laboratory has shown that in primates the perceived intensity of a train of deflections is correlated with somatosensory cortical firing rate. We predicted therefore that the presence of frequency and amplitude noise would increase response magnitude in human subjects, and that this would lead to an increase in perceived intensity, as compared to matched constant-amplitude or constant-frequency stimuli. We tested this prediction in a series of psychophysical experiments. For each subject, the threshold for detection of amplitude and frequency noise was estimated using a 2-interval forced choice (2AFC) noise detection task. A sub-threshold level of noise was used in the subsequent task. In a standard staircase procedure, subjects were asked to discriminate the intensity of pairs of vibrations delivered to their fingertip in a 2AFC paradigm in which one of the vibrations always had either amplitude or frequency noise while the other vibration did not. The key finding is that, although subjects were unaware of the noise, its presence still caused them to overestimate vibration intensity. Psychophysical effects were comparable '' in the magnitude and direction of perceptual bias '' with those predicted if the physiological effects of stimulus noise seen in barrel cortex were to generalize directly to humans. The main conclusions are that neurons in rat barrel cortex are ''tuned'' to respond in a different way to stimulus trains characterized by temporal and amplitude unpredictability, and that physiological phenomena from barrel cortex can be directly transferred to human tactile system to test hypotheses of perceptual mechanisms. Conference: Computational and systems neuroscience 2009, Salt Lake City, UT, United States, 26 Feb - 3 Mar, 2009. Presentation Type: Poster Presentation Topic: Poster Presentations Citation: (2009). Correlated physiological and perceptual effects of noise in a tactile stimulus. Front. Syst. Neurosci. Conference Abstract: Computational and systems neuroscience 2009. doi: 10.3389/conf.neuro.06.2009.03.278 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 04 Feb 2009; Published Online: 04 Feb 2009. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract Supplemental Data The Authors in Frontiers Google Google Scholar PubMed Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. 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Enhanced Response of Neurons in Rat Somatosensory Cortex to Stimuli Containing Temporal Noise

Sensory stimuli under natural conditions often consist of a temporally irregular sequence of events, contrasting with the periodic sequences commonly used as stimuli in the laboratory. These experiments compared the responses of neurons in rat barrel cortex with trains of whisker movements with different frequencies; each train possessed either a periodic or an irregular, "noisy" temporal structure. Periodic stimulus trains were composed of a sequence of 21 whisker deflections separated by 20 equal interdeflection intervals (IDIs). Noisy trains were matched for mean IDI but included intervals shorter and longer than the mean IDI. Cortical responses were equivalent for periodic and noisy stimuli for frequencies up to 10 Hz. Above 10 Hz, temporal noise led to a larger response magnitude, and this effect was amplified as deflection frequency increased. Noise also caused a sharpening of the temporal precision of response to the individual deflections of the stimulus train. Cortical neurons thus appear to be "tuned" to respond in a different way to stimuli characterized by temporal unpredictability. As a consequence, perceptual judgments that depend on somatosensory cortical firing rate may be affected by the presence of temporal noise.