Rat Somatosensory Cortex Research Articles

An Automated Classification Method for Single Sweep Local Field Potentials Recorded from Rat Barrel Cortex under Mechanical Whisker Stimulation

Understanding brain signals as an outcome of brain’s information processing is a challenge for the neuroscience and neuroengineering community. Rodents sense and explore the environment through whisking. The local field potentials (LFPs) recorded from the barrel 28 columns of the rat somatosensory cortex (S1) during whisking provide information about the tactile information processing pathway. Particularly when using large-scale high-resolution neuronal probes, during each experiment many single LFPs are recorded as an outcome of underlying neuronal network activation and averaged to extract information. However, single LFP signals are frequently very different from each other and extracting information provided by their shape is a useful way to better decode information transmitted by the network. In this work, we propose an automated method capable of classifying these signals based on their shapes. We used template matching approach to recognize single LFPs and extracted the contour information from the recognized signal to generate a feature matrix, which is then classified using the intelligent K–means clustering. As an application example, shape specific information (e.g., latency, and amplitude) of LFPs evoked in the rat somatosensory barrel cortex and used in decoding the rat whiskers information processing pathway is provided by the method.

Pharmacological modulation of functional connectivity: α2-adrenergic receptor agonist alters synchrony but not neural activation

Correlative low frequency fluctuations in functional MRI (fMRI) signals across brain regions at rest have been taken as a measure of functional connectivity to map large-scale neural networks; however, the neural origin is still not clear. Receptor-targeted pharmacological manipulation could elucidate the role of neuroreceptor systems in resting-state functional connectivity to provide another perspective on the mechanism. In this study, the dose-dependent effects of an α(2)-adrenergic receptor agonist, medetomidine, on brain activation and functional connectivity were investigated. Forepaw stimulation-induced activation and resting-state fluctuation in the rat somatosensory cortices and caudate putamen were measured using the blood oxygenation level dependent (BOLD) fMRI. The results showed significant dose-dependent suppression of inter-hemispheric correlation but not the amplitude in the somatosensory areas, while the stimulation-induced activation in the same areas remained unchanged. To clarify the potential change in the hemodynamic response caused by the vasoconstrictive effect of medetomidine, the resting perfusion fluctuation was studied by arterial spin labeling and showed similar results as the BOLD. This suggests that the oxygen metabolic rate and hence the neural activity may not be affected by medetomidine but only the synchrony between brain regions was suppressed. Furthermore, no change in functional connectivity with medetomidine dosages was seen in the caudate putamen, a region with much lower α(2)-receptor density. These results indicate that resting-state signal correlation may reflect underlying neuroreceptor activity and a potential role of the adrenergic system in the functional connectivity.

Brain-specific interleukin-1 receptor accessory protein in sleep regulation

Interleukin (IL)-1β is involved in several brain functions, including sleep regulation. It promotes non-rapid eye movement (NREM) sleep via the IL-1 type I receptor. IL-1β/IL-1 receptor complex signaling requires adaptor proteins, e.g., the IL-1 receptor brain-specific accessory protein (AcPb). We have cloned and characterized rat AcPb, which shares substantial homologies with mouse AcPb and, compared with AcP, is preferentially expressed in the brain. Furthermore, rat somatosensory cortex AcPb mRNA varied across the day with sleep propensity, increased after sleep deprivation, and was induced by somnogenic doses of IL-1β. Duration of NREM sleep was slightly shorter and duration of REM sleep was slightly longer in AcPb knockout than wild-type mice. In response to lipopolysaccharide, which is used to induce IL-1β, sleep responses were exaggerated in AcPb knockout mice, suggesting that, in normal mice, inflammation-mediated sleep responses are attenuated by AcPb. We conclude that AcPb has a role in sleep responses to inflammatory stimuli and, possibly, in physiological sleep regulation.

Parallel Regulation of Feedforward Inhibition and Excitation during Whisker Map Plasticity

Sensory experience drives robust plasticity of sensory maps in cerebral cortex, but the role of inhibitory circuits in this process is not fully understood. We show that classical deprivation-induced whisker map plasticity in layer 2/3 (L2/3) of rat somatosensory (S1) cortex involves robust weakening of L4-L2/3 feedforward inhibition. This weakening was caused by reduced L4 excitation onto L2/3 fast-spiking (FS) interneurons, which mediate sensitive feedforward inhibition and was partially offset by strengthening of unitary FS to L2/3 pyramidal cell synapses. Weakening of feedforward inhibition paralleled the known weakening of feedforward excitation. As a result, mean excitation-inhibition balance and timing onto L2/3 pyramidal cells were preserved. Thus, reduced feedforward inhibition is a covert compensatory process that can maintain excitatory-inhibitory balance during classical deprivation-induced Hebbian map plasticity.

Early and Late Stimulus-Evoked Cortical Hemodynamic Responses Provide Insight into the Neurogenic Nature of Neurovascular Coupling

Understanding neurovascular coupling is a prerequisite for the interpretation of results obtained from modern neuroimaging techniques. This study investigated the hemodynamic and neural responses in rat somatosensory cortex elicited by 16 seconds electrical whisker stimuli. Hemodynamics were measured by optical imaging spectroscopy and neural activity by multichannel electrophysiology. Previous studies have suggested that the whisker-evoked hemodynamic response contains two mechanisms, a transient 'backwards' dilation of the middle cerebral artery, followed by an increase in blood volume localized to the site of neural activity. To distinguish between the mechanisms responsible for these aspects of the response, we presented whisker stimuli during normocapnia ('control'), and during a high level of hypercapnia. Hypercapnia was used to 'predilate' arteries and thus possibly 'inhibit' aspects of the response related to the 'early' mechanism. Indeed, hemodynamic data suggested that the transient stimulus-evoked response was absent under hypercapnia. However, evoked neural responses were also altered during hypercapnia and convolution of the neural responses from both the normocapnic and hypercapnic conditions with a canonical impulse response function, suggested that neurovascular coupling was similar in both conditions. Although data did not clearly dissociate early and late vascular responses, they suggest that the neurovascular coupling relationship is neurogenic in origin.

Effect of chronic morphine treatment on tactile learning in rat

In our previous study, we reported that chronic morphine exposure changes neuronal response properties in rat somatosensory cortex. In this study, we investigated the effect of chronic morphine treatment on tactile learning behavior in rats. Morphine sulfate was dissolved in tap water, and was administered for 21 days. Tactile learning was assessed using the novel object recognition test (NORT) in a dark room. The chronic morphine treated group exhibited a learning impairment; the discrimination ratio was significantly lower as compared to the control group. These findings suggest that chronic exposure to morphine impaired the tactile learning in rats as the discrimination ratio was decreased following morphine administration.

Stimulus-induced reduction of noise correlation in rat prefrontal cortex

We have shown previously that stimulus-induced modulation of noise correlation in rat somatosensory cortex conveys additional information about the delivery of tactile stimulation. Here we investigated whether noise correlation is also modulated by an external sensory stimulus in rat prefrontal cortex and, if so, whether such modulation conveys additional information on stimulus delivery. Noise correlation was significantly reduced after the onset of a conditional stimulus (auditory tone) that signaled an electric foot shock in the prefrontal cortex. However, noise correlation contributed little to the transmission of information on stimulus delivery. These results indicate that a meaningful sensory stimulus reduces noise correlation in rat prefrontal cortex, but such modulation does not play a significant role in conveying information on stimulus delivery.

Self-organising criticality in the simulated models of the rat cortical microcircuits

Two and three dimensional models of rat barrel and somatosensory cortex were simulated. Hoddgkin–Huxley and Leaky-Integrate-and-Fire neurons were used to the construction of the networks in GENESIS and PCSIM environments. The dynamics of both models was analysed. Self-organising criticality phenomena were found. Profound investigations of this behaviour showed its dependence not only on the number of connections, but also on the simulated network architecture originating, e.g., from varying probability of exocytosis or synapse creation in the selected areas of the network. For two dimensional model the results were compared to that obtained for smaller models and analysis of this comparison is presented to some extent. The three dimensional model of the rat primary somatosensory cortex is based on the ensemble of Liquid State Machines. The results obtained from that model are in good agreement with the dynamics recorded in neurophysiological experiments on real brain.

Measurements and Modeling of Transient Blood Flow Perturbations Induced by Brief Somatosensory Stimulation

Proper interpretation of BOLD fMRI and other common functional imaging methods requires an understanding of neurovascular coupling. We used laser speckle-contrast optical imaging to measure blood-flow responses in rat somatosensory cortex elicited by brief (2 s) forepaw stimulation. Results show a large increase in local blood flow speed followed by an undershoot and possible late-time oscillations. The blood flow measurements were modeled using the impulse response of a simple linear network, a four-element windkessel. This model yielded excellent fits to the detailed time courses of activated regions. The four-element windkessel model thus provides a simple explanation and interpretation of the transient blood-flow response, both its initial peak and its late-time behavior.

Evidence for structural and functional changes of subplate neurons in developing rat barrel cortex

In the developing sensory cortex, the subplate could serve as a transient relay station between the thalamus and cortical plate and assists the formation of thalamocortical projection. While the thalamus-layer IV connection is formed, the thalamic activation of subplate is diminished. In the present study, we aimed to explore the mechanism which may attribute to the decline of subplate activity. To resolve this issue, the developmental changes of subplate neurons (SPns) in rat somatosensory cortex were examined during the first two postnatal weeks which covers the stages prior and subsequent to the establishment of thalamocortical connection. During development, more SPns exhibited regular-spiking firing pattern and the membrane properties of SPns displayed a continual trend of maturation. In the meantime, the excitability of SPns decreased as revealed by increasing rheobase and rightwardly shifted frequency-current curves. On the other hand, increasing paired-pulse ratio and slowing MK-801 blocking rate were noted during development, implying the reduction of presynaptic transmitter release. Morphologically, the size of SPn soma increased with age while the shape became flat. The total length, branching nodes and segments of dendrites increased significantly during the first week. However, after peaking around day 10, these values decreased, implying a pruning process. Our findings here propose that the reduction of neuronal excitability, synaptic transmission and dendritic complexity may attribute to the decline of functional connectivity between thalamus and subplate and reduction of subplate activity while the thalamocortical pathway is established.

Cortical Excitation and Inhibition following Focal Traumatic Brain Injury

Cortical compression can be a significant problem in many types of brain injuries, such as brain trauma, localized brain edema, hematoma, focal cerebral ischemia, or brain tumors. Mechanical and cellular alterations can result in global changes in excitation and inhibition on the neuronal network level even in the absence of histologically significant cell injury, often manifesting clinically as seizures. Despite the importance and prevalence of this problem, however, the precise electrophysiological effects of brain injury have not been well characterized. In this study, the changes in electrophysiology were characterized following sustained cortical compression using large-scale, multielectrode measurement of multiunit activity in primary somatosensory cortex in a sensory-evoked, in vivo animal model. Immediately following the initiation of injury at a distal site, there was a period of suppression of the evoked response in the rat somatosensory cortex, followed by hyper-excitability that was accompanied by an increase in the spatial extent of cortical activation. Paired-pulse tactile stimulation revealed a dramatic shift in the excitatory/inhibitory dynamics, suggesting a longer term hyperexcitability of the cortical circuit following the initial suppression that could be linked to the disruption of one or more inhibitory mechanisms of the thalamocortical circuit. Together, our results showed that the use of a sensory-evoked response provided a robust and repeatable functional marker of the evolution of the consequences of mild injury, serving as an important step toward in vivo quantification of alterations in excitation and inhibition in the cortex in the setting of traumatic brain injury.

Inhibitory interneurons in a cortical column form hot zones of inhibition in layers 2 and 5A

Although physiological data on microcircuits involving a few inhibitory neurons in the mammalian cerebral cortex are available, data on the quantitative relation between inhibition and excitation in cortical circuits involving thousands of neurons are largely missing. Because the distribution of neurons is very inhomogeneous in the cerebral cortex, it is critical to map all neurons in a given volume rather than to rely on sparse sampling methods. Here, we report the comprehensive mapping of interneurons (INs) in cortical columns of rat somatosensory cortex, immunolabeled for neuron-specific nuclear protein and glutamate decarboxylase. We found that a column contains ~2,200 INs (11.5% of ~19,000 neurons), almost a factor of 2 less than previously estimated. The density of GABAergic neurons was inhomogeneous between layers, with peaks in the upper third of L2/3 and in L5A. IN density therefore defines a distinct layer 2 in the sensory neocortex. In addition, immunohistochemical markers of IN subtypes were layer-specific. The "hot zones" of inhibition in L2 and L5A match the reported low stimulus-evoked spiking rates of excitatory neurons in these layers, suggesting that these inhibitory hot zones substantially suppress activity in the neocortex.

A processing work-flow for measuring erythrocytes velocity in extended vascular networks from wide field high-resolution optical imaging data

Comprehensive information on the spatio-temporal dynamics of the vascular response is needed to underpin the signals used in hemodynamics-based functional imaging. It has recently been shown that red blood cells (RBCs) velocity and its changes can be extracted from wide-field optical imaging recordings of intrinsic absorption changes in cortex. Here, we describe a complete processing work-flow for reliable RBC velocity estimation in cortical networks. Several pre-processing steps are implemented: image co-registration, necessary to correct for small movements of the vasculature, semi-automatic image segmentation for fast and reproducible vessel selection, reconstruction of RBC trajectories patterns for each micro-vessel, and spatio-temporal filtering to enhance the desired data characteristics. The main analysis step is composed of two robust algorithms for estimating the RBCs' velocity field. Vessel diameter and its changes are also estimated, as well as local changes in backscattered light intensity. This full processing chain is implemented with a software suite that is freely distributed. The software uses efficient data management for handling the very large data sets obtained with in vivo optical imaging. It offers a complete and user-friendly graphical user interface with visualization tools for displaying and exploring data and results. A full data simulation framework is also provided in order to optimize the performances of the algorithm with respect to several characteristics of the data. We illustrate the performance of our method in three different cases of in vivo data. We first document the massive RBC speed response evoked by a spreading depression in anesthetized rat somato-sensory cortex. Second, we show the velocity response elicited by a visual stimulation in anesthetized cat visual cortex. Finally, we report, for the first time, visually-evoked RBC speed responses in an extended vascular network in awake monkey extrastriate cortex.

Localization of single barrel column by means of a volumetric current source density analysis in the somatosensory cortex of rat

Localization of single barrel column by means of a volumetric current source density analysis in the somatosensory cortex of rat

Stereotypical spatiotemporal activity patterns during slow-wave activity in the neocortex

Alternating epochs of activity and silence are a characteristic feature of neocortical networks during certain sleep cycles and deep states of anesthesia. The mechanism and functional role of these slow oscillations (<1 Hz) have not yet been fully characterized. Experimental and theoretical studies show that slow-wave oscillations can be generated autonomously by neocortical tissue but become more regular through a thalamo-cortical feedback loop. Evidence for a functional role of slow-wave activity comes from EEG recordings in humans during sleep, which show that activity travels as stereotypical waves over the entire brain, thought to play a role in memory consolidation. We used an animal model to investigate activity wave propagation on a smaller scale, namely within the rat somatosensory cortex. Signals from multiple extracellular microelectrodes in combination with one intracellular recording in the anesthetized animal in vivo were utilized to monitor the spreading of activity. We found that activity propagation in most animals showed a clear preferred direction, suggesting that it often originated from a similar location in the cortex. In addition, the breakdown of active states followed a similar pattern with slightly weaker direction preference but a clear correlation to the direction of activity spreading, supporting the notion of a wave-like phenomenon similar to that observed after strong sensory stimulation in sensory areas. Taken together, our findings support the idea that activity waves during slow-wave sleep do not occur spontaneously at random locations within the network, as was suggested previously, but follow preferred synaptic pathways on a small spatial scale.

Broadband Local Field Potentials Correlate with Spontaneous Fluctuations in Functional Magnetic Resonance Imaging Signals in the Rat Somatosensory Cortex Under Isoflurane Anesthesia

Resting-state functional magnetic resonance imaging (fMRI) is widely used for exploring spontaneous brain activity and large-scale networks; however, the neural processes underlying the observed resting-state fMRI signals are not fully understood. To investigate the neural correlates of spontaneous low-frequency fMRI fluctuations and functional connectivity, we developed a rat model of simultaneous fMRI and multiple-site intracortical neural recordings. This allowed a direct comparison to be made between the spontaneous signals and interhemispheric connectivity measured with the two modalities. Results show that low-frequency blood oxygen level-dependent (BOLD) fluctuations (<0.1 Hz) correlate significantly with slow power modulations (<0.1 Hz) of local field potentials (LFPs) in a broad frequency range (1-100 Hz) under isoflurane anesthesia (1%-1.8%). Peak correlation occurred between neural and hemodynamic activity when the BOLD signal was delayed by ~4 sec relative to the LFP signal. The spatial location and extent of correlation was highly reproducible across studies, with the maximum correlation localized to a small area surrounding the site of microelectrode recording and to the homologous area in the contralateral hemisphere for most rats. Interhemispheric connectivity was calculated using BOLD correlation and band-limited LFP (1-4, 4-8, 8-14, 14-25, 25-40, and 40-100 Hz) coherence. Significant coherence was observed for the slow power changes of all LFP frequency bands as well as in the low-frequency BOLD data. A preliminary investigation of the effect of anesthesia on interhemispheric connectivity indicates that coherence in the high-frequency LFP bands declines with increasing doses of isoflurane, whereas coherence in the low-frequency LFP bands and the BOLD signal increases. These findings suggest that resting-state fMRI signals might be a reflection of broadband LFP power modulation, at least in isoflurane-anesthetized rats.

Simultaneous measurements of glucose, oxyhemoglobin and deoxyhemoglobin in exposed rat cortex

The present work addresses the simultaneous monitoring of hemoglobin and glucose consumption in rat somatosensory cortex in vivo. We propose a method which combines two techniques: 2-dimensional optical imaging and an amperometric microbiosensor. The mounted setup optimizes the space in the cranial window so that three micro-electrodes can be inserted: glucose microbiosensor, sentinel and stimulating electrode as well as the holder to manipulate the optical fiber. Additionally, a tool based on graphical user interface programming has been developed to visualize a two-dimension spectral map of oxy-, deoxy- and total hemoglobin, HbO 2, HbR and HbT respectively, in the cortex. Our results showed a good sensitivity, selectivity and spatial resolution for both methods. Relevant hemodynamic responses had a common central focus (at the site of the stimulus) which later segregated to other vascular compartments. A good linear relationship between extracellular glucose concentration and HbO 2 values during brain activation after local electrical stimulation was observed for electrochemical and optical recordings ( R 2 values were over 0.94). Time courses between glucose and HbO 2 signals showed a temporal delay ranging from 1 s to 2 s, suggesting that both variables are not always coupled. The temporal mismatching reported here, provides in vivo evidence that supports a neuronal hypothesis: cerebral blow flow and oxidative metabolism are driven in parallel by neural activity – rather than a concatenation of events (‘in-series’ events) occurring at sites of neuronal activation.

Laminar population analysis of multielectrode recordings from rat primary auditory cortex

The technology for large-scale electrical recordings is rapidly improving, and extracellular recordings with multielectrode arrays now offer a unique window into neural activity at the population level. The high-frequency part of the recorded signal (MUA; multi-unit activity) is a measure of action-potential firing of neurons in the immediate vicinity of the electrode contacts, while the low-frequency part (LFP; local-field potential) appears to mainly be a measure of subthreshold dendritic activity of surrounding neurons [1,2]. The interpretation of MUA and LFP signals in terms of neural circuit activity is not straightforward, however, and new analysis methods are needed to take full advantage of the technological developments. Laminar population analysis (LPA) [1] was introduced a few years ago as a new method for extracting information about population activity. Based on physiologically-constrained joint modeling of the MUA and LFP signals, both the (i) laminar organization and time-resolved firing rates of the main cortical populations, and (ii) the functional synaptic connection patterns between these populations, were estimated. Later, the population firing-rates extracted by means of LPA were used to specify mathematical neural-network models describing thalamocortical and intracortical connections between neural populations in the rat somatosensory (barrel) system [3]. In Ref. [1] LPA was used to analyze stimulus-averaged laminar (linear) electrode data from the rat barrel system, and the predicted time-resolved population firing rates and synaptic connection patterns were found to be in qualitative agreement with previous experimental findings. Here we apply LPA to recently recorded laminar-electrode data from the primary auditory cortex of rats [4]. In this study the rats were exposed to a large variety of different auditory stimuli to investigate the phenomenon known as ‘stimulus-specific adaptation’, i.e., that neurons respond stronger to unexpected stimuli. Such rich data sets where the cortical neural circuits of interest potentially exhibit a large variety of activation patterns, are particularly well suited for analysis by means of LPA. Results from LPA analysis will be presented, highlighting the differences and similarities seen between the sensory-evoked cortical response patterns in primary auditory and somatosensory cortices of rats.

Network dynamics associated with experience-dependent plasticity in the rat somatosensory cortex

Experience-dependent plasticity is hypothesized to occur in the rat barrel cortex as a result of whisker pairing induced by depriving all but two whiskers. A significant change in the response of individual neurons in the barrels of the spared whiskers is observed compared to their response before pairing. The over-usage of the spared whiskers results in an increased similarity in the sensory-evoked response of the neurons in the barrels of spared whiskers that may indicate an actual merging of the two barrels. The goal of this study is to examine the application of Dynamic Bayesian Networks (DBNs) in tracking the network dynamics associated with this type of plasticity in layer V of the rat barrel cortex. DBN is an efficient graphical model that fits the observed spike train data by explaining the temporally precise spiking of each observed neuron while accounting for the spiking pattern of the entire observed population. We have recently demonstrated the effectiveness of DBN to infer stimulus-specific networks in the rat barrel cortex in response to the stimulation of individual whiskers. This form of network coding provides more information about the stimulus than both rate and temporal codes. In this study, we examined the changes that occur to these stimulus-specific networks as a result of whisker pairing. In 4 subjects, 32-channel multi-electrode arrays were chronically implanted to record from layer V of the barrel cortex. One week post implantation, sensory-evoked activity was recorded (control data) over a number of days after which all but two whiskers on one side of the rat’s mystacial pad were trimmed. Sensory-evoked activity was then recorded 1 to 2 days and 6 to 7 days post-trimming (plasticity data). Spike trains within 100 ms of stimulus onset of both control and plasticity data for each of the spared whiskers were then analyzed using DBN to infer stimulus-specific causal networks. To assess plasticity at the individual neuron level, the number of evoked spikes by the neurons as well as the first-spike latency in response to the deflection of each of the spared whiskers were measured for both control and plasticity data. The difference in the number of evoked spikes and in the first-spike latency across the spared whiskers was found to decrease significantly 6 to 7 days post whisker trimming (Normalized difference in evoked spikes for control data: 0.41±0.23, 6-7 days post-trimming: 0.29±0.21; Normalized difference in first-spike latency for control data: 0.18±0.12, 6-7 days post-trimming: 0.15±0.11, P < 0.05, paired t-test). This indicates an increased similarity in the response of individual neurons to the spared whiskers as a result of the pairing. At the network level, a significant increase in the similarity between the stimulus-specific networks across the spared whiskers was observed that is proportional to the number of days of whisker pairing (Network similarity for control data: 0.58±0.1, 1-2 days post-trimming: 0.66±0.1, 6-7 days post-trimming: 0.71±0.1, P < 0.05, paired t-test). This finding suggests an experience-dependent plastic change in the neuronal networks of layer V that is consistent with Hebbian plasticity.

Effective neuronal refractoriness dominates the statistics of superimposed spike trains

The pooled spike trains of populations of neurons are typically modeled as Poisson processes [2]. It is known, though, that the superposition of point processes is a Poisson process if and only if all components are Poisson processes [3]. However, neocortical neurons spike more regularly [1]. Partly this is because they often have a refractory period, but also because the membrane potential is hyperpolarized after each spike, as illustrated in Figure ​Figure1A.1A. Here we analyze neuronal spike trains recorded intracellularly in vivo from rat somatosensory cortex. We match them with a Poisson process with dead-time [4], which is the simplest model of neuronal activity that incorporates refractory effects. The dead-time here models the effective refractoriness of the neuron, which can be larger than the refractory period due to channel kinetics alone. From the spike train recordings we construct independent superpositions (see Figure ​Figure1B)1B) and compare their statistics to our analytical results for the model processes. We find that the effective refractoriness of the neurons dominates the second-order statistics of the superposition spike trains. We uncover profound statistical differences as compared to Poisson processes, which considerably affect the dynamics of the membrane potential of neurons that receive such superpositions, as we further show in numerical simulations (see also [5]). Figure 1 A: Membrane potential trajectories of a simulated neocortical neuron. After each spike, the potential has to charge up until spikes can be initiated by input fluctuations, leading to an effective refractoriness. Green line shows the mean subthreshold ...