Local Field Potential Activity Research Articles

Local Field Potentials: Myths and Misunderstandings.

The intracerebral local field potential (LFP) is a measure of brain activity that reflects the highly dynamic flow of information across neural networks. This is a composite signal that receives contributions from multiple neural sources, yet interpreting its nature and significance may be hindered by several confounding factors and technical limitations. By and large, the main factor defining the amplitude of LFPs is the geometry of the current sources, over and above the degree of synchronization or the properties of the media. As such, similar levels of activity may result in potentials that differ in several orders of magnitude in different populations. The geometry of these sources has been experimentally inaccessible until intracerebral high density recordings enabled the co-activating sources to be revealed. Without this information, it has proven difficult to interpret a century's worth of recordings that used temporal cues alone, such as event or spike related potentials and frequency bands. Meanwhile, a collection of biophysically ill-founded concepts have been considered legitimate, which can now be corrected in the light of recent advances. The relationship of LFPs to their sources is often counterintuitive. For instance, most LFP activity is not local but remote, it may be larger further from rather than close to the source, the polarity does not define its excitatory or inhibitory nature, and the amplitude may increase when source's activity is reduced. As technological developments foster the use of LFPs, the time is now ripe to raise awareness of the need to take into account spatial aspects of these signals and of the errors derived from neglecting to do so.

Nasal Respiration Entrains Human Limbic Oscillations and Modulates Cognitive Function.

Animal studies have long shown that olfactory oscillatory activity emerges in line with the natural rhythm of breathing, even in the absence of an odor stimulus. Whether the breathing cycle induces cortical oscillations in the human brain is poorly understood. In this study, we collected intracranial EEG data from rare patients with medically intractable epilepsy, and found evidence for respiratory entrainment of local field potential activity in human piriform cortex, amygdala, and hippocampus. These effects diminished when breathing was diverted to the mouth, highlighting the importance of nasal airflow for generating respiratory oscillations. Finally, behavioral data in healthy subjects suggest that breathing phase systematically influences cognitive tasks related to amygdala and hippocampal functions.

Striatal Dopaminergic Innervation Regulates Subthalamic Beta-Oscillations and Cortical-Subcortical Coupling during Movements: Preliminary Evidence in Subjects with Parkinson's Disease.

Activation of the basal ganglia has been shown during the preparation and execution of movement. However, the functional interaction of cortical and subcortical brain areas during movement and the relative contribution of dopaminergic striatal innervation remains unclear. We recorded local field potential (LFP) activity from the subthalamic nucleus (STN) and high-density electroencephalography (EEG) signals in four patients with Parkinson’s disease (PD) off dopaminergic medication during a multi-joint motor task performed with their dominant and non-dominant hand. Recordings were performed by means of a fully-implantable deep brain stimulation (DBS) device at 4 months after surgery. Three patients also performed a single-photon computed tomography (SPECT) with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (FP-CIT) to assess striatal dopaminergic innervation. Unilateral movement execution led to event-related desynchronization (ERD) followed by a rebound after movement termination event-related synchronization (ERS) of oscillatory beta activity in the STN and primary sensorimotor cortex of both hemispheres. Dopamine deficiency directly influenced movement-related beta-modulation, with greater beta-suppression in the most dopamine-depleted hemisphere for both ipsi- and contralateral hand movements. Cortical-subcortical, but not interhemispheric subcortical coherencies were modulated by movement and influenced by striatal dopaminergic innervation, being stronger in the most dopamine-depleted hemisphere. The data are consistent with a role of dopamine in shielding subcortical structures from an excessive cortical entrapment and cross-hemispheric coupling, thus allowing fine-tuning of movement.

Decoding gripping force based on local field potentials recorded from subthalamic nucleus in humans

The basal ganglia are known to be involved in the planning, execution and control of gripping force and movement vigour. Here we aim to define the nature of the basal ganglia control signal for force and to decode gripping force based on local field potential (LFP) activities recorded from the subthalamic nucleus (STN) in patients with deep brain stimulation (DBS) electrodes. We found that STN LFP activities in the gamma (55-90 Hz) and beta (13-30m Hz) bands were most informative about gripping force, and that a first order dynamic linear model with these STN LFP features as inputs can be used to decode the temporal profile of gripping force. Our results enhance the understanding of how the basal ganglia control gripping force, and also suggest that deep brain LFPs could potentially be used to decode movement parameters related to force and movement vigour for the development of advanced human-machine interfaces.

Temporal coding of reward-guided choice in the posterior parietal cortex

Making a decision involves computations across distributed cortical and subcortical networks. How such distributed processing is performed remains unclear. We test how the encoding of choice in a key decision-making node, the posterior parietal cortex (PPC), depends on the temporal structure of the surrounding population activity. We recorded spiking and local field potential (LFP) activity in the PPC while two rhesus macaques performed a decision-making task. We quantified the mutual information that neurons carried about an upcoming choice and its dependence on LFP activity. The spiking of PPC neurons was correlated with LFP phases at three distinct time scales in the theta, beta, and gamma frequency bands. Importantly, activity at these time scales encoded upcoming decisions differently. Choice information contained in neural firing varied with the phase of beta and gamma activity. For gamma activity, maximum choice information occurred at the same phase as the maximum spike count. However, for beta activity, choice information and spike count were greatest at different phases. In contrast, theta activity did not modulate the encoding properties of PPC units directly but was correlated with beta and gamma activity through cross-frequency coupling. We propose that the relative timing of local spiking and choice information reveals temporal reference frames for computations in either local or large-scale decision networks. Differences between the timing of task information and activity patterns may be a general signature of distributed processing across large-scale networks.

Early hippocampal hyperexcitability in PS2APP mice: role of mutant PS2 and APP

Alterations of brain network activity are observable in Alzheimer's disease (AD) together with the occurrence of mild cognitive impairment, before overt pathology. However, in humans as well in AD mouse models, identification of early biomarkers of network dysfunction is still at its beginning. We performed in vivo recordings of local field potential activity in the dentate gyrus of PS2APP mice expressing the human amyloid precursor protein (APP) Swedish mutation and the presenilin-2 (PS2) N141I. From a frequency-domain analysis, we uncovered network hyper-synchronicity as early as 3 months, when intracellular accumulation of amyloid beta was also observable. In addition, at 6 months of age, we identified network hyperactivity in the beta/gamma frequency bands, along with increased theta-beta and theta-gamma phase-amplitude cross-frequency coupling, in coincidence with the histopathological traits of the disease. Although hyperactivity and hypersynchronicity were respectively detected in mice expressing the PS2-N141I or the APP Swedish mutant alone, the increase in cross-frequency coupling specifically characterized the 6-month-old PS2APP mice, just before the surge of the cognitive decline.

Dysregulated corticostriatal activity in open-field behavior and the head-twitch response induced by the hallucinogen 2,5-dimethoxy-4-iodoamphetamine

The substituted amphetamine, 2,5-dimethoxy-4-iodoamphetamine (DOI), is a hallucinogen that has been used to model a variety of psychiatric conditions. Here, we studied the effect of DOI on neural activity recorded simultaneously in the primary motor cortex (M1) and dorsal striatum of freely behaving FvB/N mice. DOI significantly decreased the firing rate of individually isolated neurons in M1 and dorsal striatum relative to pre-drug baseline. It also induced a bursting pattern of activity by increasing both the number of spikes within a burst and burst duration. In addition, DOI increased coincident firing between simultaneously recorded neuron pairs within the striatum and between M1 and dorsal striatum. Local field potential (LFP) activity also increased in coherence between M1 and dorsal striatum after DOI in the low frequency gamma band (30–50 Hz), while corticostriatal coherence in delta, theta, alpha, and beta activity decreased. We also assessed corticostriatal LFP activity in relation to the DOI-induced head-twitch response (HTR), a readily identifiable behavior used to assess potential treatments for the conditions it models. The HTR was associated with increased delta and decreased theta power in both M1 and dorsal striatum. Together, our results suggest that DOI dysregulates corticostriatal communication and that the HTR is associated with this dysregulation.

The Effects of Mechanical and Thermal Stimuli on Local Field Potentials and Single Unit Activity in Parkinson’s Disease Patients

Chronic pain is a major, debilitating symptom of Parkinson's disease (PD). Although, deep brain stimulation (DBS) has been shown to improve pain outcomes, the mechanisms underlying this phenomenon are unclear. Microelectrode recording allows us to measure both local field potentials (LFPs) and single neuronal unit activity (SUA). In this study, we examined how single unit and LFP oscillatory activity in the basal ganglia are impacted by mechanical and thermal sensory stimuli and explored their role in pain modulation. We assessed changes in LFPs and SUAs in the subthalamic nucleus (STN), globus pallidus interna (Gpi), and globus pallidus externa (Gpe) following exposure with mechanical or thermal stimuli. Sensory thresholds were determined pre-operatively using quantitative sensory testing. Based on these data, patients were exposed to innocuous and noxious mechanical, pressure, and thermal stimuli at individualized thresholds. In the STN, LFP alpha oscillatory activity and SUA increased in response to innocuous mechanical stimuli; SUA further increased in response to noxious mechanical, noxious pressure, and noxious thermal stimuli (p < 0.05). In the Gpe, LFP low betaactivity and SUA increased with noxious thermal stimuli; SUA also increased in response to innocuous thermal stimuli (p < 0.05). In the Gpi, innocuous thermal stimuli increased LFP gammaactivity; noxious pressure stimuli decreased low betaactivity; SUA increased in response to noxious thermal stimuli (p < 0.05). Our study is the first to demonstrate that mechanical and thermal stimuli alter basal ganglia LFPs and SUAs in PD. While STN SUA increases nearly uniformly to all sensory stimuli, SUA in the pallidal nuclei respond solely to thermal stimuli. Similarly, thermal stimuli yield increases in pallidal LFP activity, but not STN activity. We speculate that DBS may provide analgesia through suppression of stimuli-specific changes in basal ganglia activity, supporting a role for these nuclei in sensory and pain processing circuits.

Effects of high-frequency stimulation of the internal pallidal segment on neuronal activity in the thalamus in parkinsonian monkeys.

Deep brain stimulation of the internal globus pallidus (GPi) is a major treatment for advanced Parkinson's disease. The effects of this intervention on electrical activity patterns in targets of GPi output, specifically in the thalamus, are poorly understood. The experiments described here examined these effects using electrophysiological recordings in two Rhesus monkeys rendered moderately parkinsonian through treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), after sampling control data in the same animals. Analysis of spontaneous spiking activity of neurons in the basal ganglia-receiving areas of the ventral thalamus showed that MPTP-induced parkinsonism is associated with a reduction of firing rates of segments of the data that contained neither bursts nor decelerations, and with increased burst firing. Spectral analyses revealed an increase of power in the 3- to 13-Hz band and a reduction in the γ-range in the spiking activity of these neurons. Electrical stimulation of the ventrolateral motor territory of GPi with macroelectrodes, mimicking deep brain stimulation in parkinsonian patients (bipolar electrodes, 0.5 mm intercontact distance, biphasic stimuli, 120 Hz, 100 μs/phase, 200 μA), had antiparkinsonian effects. The stimulation markedly reduced oscillations in thalamic firing in the 13- to 30-Hz range and uncoupled the spiking activity of recorded neurons from simultaneously recorded local field potential (LFP) activity. These results confirm that oscillatory and nonoscillatory characteristics of spontaneous activity in the basal ganglia receiving ventral thalamus are altered in MPTP-induced parkinsonism. Electrical stimulation of GPi did not entrain thalamic activity but changed oscillatory activity in the ventral thalamus and altered the relationship between spikes and simultaneously recorded LFPs.

Neurovascular unit remodelling in the subacute stage of stroke recovery

Brain plasticity following focal cerebral ischaemia has been observed in both stroke survivors and in preclinical models of stroke. Endogenous neurovascular adaptation is at present incompletely understood yet its potentiation may improve long-term functional outcome. We employed longitudinal MRI, intracranial array electrophysiology, Montoya Staircase testing, and immunofluorescence to examine function of brain vessels, neurons, and glia in addition to forelimb skilled reaching during the subacute stage of ischemic injury progression. Focal ischemic stroke (~100mm3 or ~20% of the total brain volume) was induced in adult Sprague-Dawley rats via direct injection of endothelin-1 (ET-1) into the right sensori-motor cortex, producing sustained impairment in left forelimb reaching ability. Resting perfusion and vascular reactivity to hypercapnia in the peri-lesional cortex were elevated by approximately 60% and 80% respectively seven days following stroke. At the same time, the normal topological pattern of local field potential (LFP) responses to peripheral somatosensory stimulation was abolished and the average power of spontaneous LFP activity attenuated by approximately 50% relative to the contra-lesional cortex, suggesting initial response attenuation within the peri-infarct zone. By 21 days after stroke, perilesional blood flow resolved, but peri-lesional vascular reactivity remained elevated. Concomitantly, the LFP response amplitudes increased with distance from the site of ET-1 injection, suggesting functional remodelling from the core of the lesion to its periphery. This notion was further buttressed by the lateralization of spontaneous neuronal activity: by day 21, the average ipsi-lesional power of spontaneous LFP activity was almost twice that of the contra-lesional cortex. Over the observation period, the peri-lesional cortex exhibited increased vascular density, along with neuronal loss, astrocytic activation, and recruitment and activation of microglia and macrophages, with neuronal loss and inflammation extending beyond the peri-lesional cortex. These findings highlight the complex relationship between neurophysiological state and behaviour and provide evidence of highly dynamic functional changes in the peri-infarct zone weeks following the ischemic insult, suggesting an extended temporal window for therapeutic interventions.

Prefrontal Cortex Networks Shift from External to Internal Modes during Learning.

As we learn about items in our environment, their neural representations become increasingly enriched with our acquired knowledge. But there is little understanding of how network dynamics and neural processing related to external information changes as it becomes laden with "internal" memories. We sampled spiking and local field potential activity simultaneously from multiple sites in the lateral prefrontal cortex (PFC) and the hippocampus (HPC)-regions critical for sensory associations-of monkeys performing an object paired-associate learning task. We found that in the PFC, evoked potentials to, and neural information about, external sensory stimulation decreased while induced beta-band (∼11-27 Hz) oscillatory power and synchrony associated with "top-down" or internal processing increased. By contrast, the HPC showed little evidence of learning-related changes in either spiking activity or network dynamics. The results suggest that during associative learning, PFC networks shift their resources from external to internal processing. As we learn about items in our environment, their representations in our brain become increasingly enriched with our acquired "top-down" knowledge. We found that in the prefrontal cortex, but not the hippocampus, processing of external sensory inputs decreased while internal network dynamics related to top-down processing increased. The results suggest that during learning, prefrontal cortex networks shift their resources from external (sensory) to internal (memory) processing.

Reduced local field potential power in the medial prefrontal cortex by noxious stimuli.

Nociceptive signals produced by noxious stimuli at the periphery reach the brain through ascending pathways. These signals are processed by various brain areas and lead to activity changes in those areas. The medial prefrontal cortex (mPFC) is involved in higher cognitive functions and emotional processing. It receives projections from brain areas involved in nociception. In this study, we investigated how nociceptive input from the periphery changes the local field potential (LFP) activity in the mPFC. Three different types of noxious stimuli were applied to the hind paw contralateral to the LFP recording site. They were transcutaneous electrical stimulations, mechanical stimuli and a chemical stimulus (formalin injection). High intensity transcutaneous stimulations (10V to 50V) and noxious mechanical stimulus (pinch) significantly reduced the LFP power during the stimulating period (p<0.05), but not the low intensity subcutaneous stimulations (0.1V to 5V) and other innocuous mechanical stimuli (brush and pressure). More frequency bands were inhibited with increased intensity of transcutaneous electrical stimulation, and almost all frequency bands were inhibited by stimulations at or higher than 30v. Pinch significantly reduced the power for beta band and formalin injection significantly reduced the power of alpha and beta band. Our data demonstrated the noxious stimuli-induced reduction of LFP power in the mPFC, which indicates the active processing of nociceptive information by the mPFC.

Metabolic demands of neural-hemodynamic associated and disassociated areas in brain

Interpretation of regional blood oxygenation level-dependent (BOLD) responses in functional magnetic resonance imaging (fMRI) is contingent on whether local field potential (LFP) and multi-unit activity (MUA) is either dissociated or associated. To examine whether neural-hemodynamic associated and dissociated areas have different metabolic demands, we recorded sensory-evoked responses of BOLD signal, blood flow (CBF), and blood volume (CBV), which with calibrated fMRI provided oxidative metabolism (CMRO2) from rat’s ventral posterolateral thalamic nucleus (VPL) and somatosensory forelimb cortex (S1FL) and compared these neuroimaging signals to neurophysiological recordings. MUA faithfully recorded evoked latency differences between VPL and S1FL because evoked MUA in these regions were similar in magnitude. Since evoked LFP was significantly attenuated in VPL, we extracted the time courses of the weaker thalamic LFP to compare with the stronger cortical LFP using wavelet transform. BOLD and CBV responses were greater in S1FL than in VPL, similar to LFP regional differences. CBF and CMRO2 responses were both comparably larger in S1FL and VPL. Despite different levels of CBF-CMRO2 and LFP-MUA couplings in VPL and S1FL, the CMRO2 was well matched with MUA in both regions. These results suggest that neural-hemodynamic associated and dissociated areas in VPL and S1FL can have similar metabolic demands.

Decoding intravesical pressure from local field potentials in rat lumbosacral spinal cord

Chronic monitoring of intravesical pressure is required to detect the onset of intravesical hypertension and the progression of a more severe condition. Recent reports demonstrate the bladder state can be monitored from the spiking activity of the dorsal root ganglia or lumbosacral spinal cord. However, one of the most serious challenges for these methods is the difficulty of sustained spike signal acquisition due to the high-electrode-location-sensitivity of spikes or neuro-degeneration. Alternatively, it has been demonstrated that local field potential recordings are less affected by encapsulation reactions or electrode location changes. Here, we hypothesized that local field potential (LFP) from the lumbosacral dorsal horn may provide information concerning the intravesical pressure. LFP and spike activities were simultaneously recorded from the lumbosacral spinal cord of anesthetized rats during bladder filling. The results show that the LFP activities carry significant information about intravesical pressure along with spiking activities. Importantly, the intravesical pressure is decoded from the power in high-frequency bands (83.9–256 Hz) with a substantial performance similar to that of the spike train decoding. These findings demonstrate that high-frequency LFP activity can be an alternative intravesical pressure monitoring signal, which could lead to a proper closed loop system for urinary control.

Inflammatory pain by carrageenan recruits low-frequency local field potential changes in the anterior cingulate cortex

The anterior cingulate cortex (ACC) has been extensively cited as a key area for processing pain affect. While local field potential (LFP) studies in other fields have yielded a great deal of information about neural oscillations, there is a poverty in the pain literature about the neural LFP profile related to pain, particularly in freely moving animals. In this study, we revealed the LFP profile in the ACC in freely moving rats during carrageenan inflammation. Mechanical allodynia was recorded before and after unilateral injection of carrageenan/saline in the left hindpaw. LFP activity in the ACC was recorded at baseline, after injection, and after injection with mechanical stimulation to the paw using a von Frey filament. This study uniquely reveals that carrageenan injection significantly recruited ACC LFP activity in delta, theta, and alpha bands (0–13Hz). Application of von Frey mechanical stimulation to the carrageenan-injected paw resulted in a significant increase in delta, theta, and alpha bands over and above what was recruited by carrageenan alone and further expanded the LFP range to additionally include beta activity (13–30Hz). Taken together, these data reveal significant changes in the lowest-frequency activities in the LFP range during painful inflammation, which merit attention. LFP is a powerful window to reveal wide-range, integrated synaptic processing by low-frequency cellular events during behavior. Information about LFP during pain broadens the scope of our understanding of pain mechanisms, our greatest resource for designing management approaches.

EPV 15. Reward processing modulates beta activity in local field potentials of the subthalamic nucleus

In Parkinson’s disease, dopamine loss results in an increase in beta oscillations in the subthalamic nucleus that correlates well with the severity of patients’ akinetic-rigid symptoms (Kuhn et al., Experimental Neurology , 2009). There is, however, yet incomplete evidence on the functions of beta activity in the healthy brain. Given that dopamine plays an important role in the processing of rewards (Schultz et al., Science , 1997), we investigated whether beta activity might be related to reward processing. We recorded local field potentials in patients with Parkinson’s disease, while these patients performed a computer-based reinforcement learning task. In each trial, patients had to choose one out of three possible joystick movements (left, right, up). Afterwards, a reward signal (number between 0 and 10) was presented. Each movement direction was associated with a reward probability curve, where curves differed in means. After intervals of approximately 20 trials, reward probability curves were randomly reassigned between joystick movements. Patients were asked to choose joystick movements such as to maximize reward points. Event-related modulation in STN oscillatory activity was analyzed with respect to reward presentation and movement execution and correlated with the magnitudes of observed rewards across trials. We found a significant positive correlation (rho = 0.23, p = 0.006) between reward magnitudes and beta activity during the time interval of reward presentation. Moreover, we found a significant negative correlation (rho = −0.20, p = 0.045) between reward magnitudes and alpha activity during the movements following the rewards (i.e., the subsequent-trial movements). These results suggest a role of beta activity in the processing of rewards, while alpha activity might be related to the reward-based adaptation of motor responses.

EP 103. Gait specific modulation of local field potentials in the STN of patients with Parkinson’s disease

PD patients with implanted DBS electrodes allow for the investigation of basal ganglia activity during gait. Whereas the overall spectral content of local field potentials (LFP) in the BG is known to change with movement, it is still unclear how exactly the BG-LFP change during gait. We investigated the electric local field potentials of the STN of 10 patients with PD during gait. Gait parameters were recorded with inertial sensor units and the gait was subsequently analyzed in parallel to the electrophysiological activity in Matlab. Additionally, we recorded LFPs during rest and control experiments to probe for movement related artifacts. Stimulation was off in all experiments reported here. On a group level, a frequency analysis shows that the high beta frequency band gets significantly downregulated during gait as compared to sitting rest. On an individual level, a linear classifier trained with frequency profiles of small epochs of LFP activity recorded during gait and rest can distinguish between walking and resting episodes with a mean classification accuracy across all patients of 90%. A time–frequency analysis on the group level reveals a distinct modulation pattern. Whereas low frequencies in the theta and alpha range and high frequencies in the gamma range are modulated up and down time-locked to the gait cycle, the beta band gets modulated down during the complete gait cycle.

A review of electrodes for the electrical brain signal recording

Brain is complex organ composed of numerous glial cells and neurons to convey information using chemical and electrical signals. Neural interface technology using the electrical brain signals has attracted great attention for the clinical and experimental applications. Electrode as the neural interface is the most important part in stimulating neural cells or recording neural activities. In this paper, we provide an overview of electrodes for recording the electrical brain signal. The noninvasive electrodes are primarily used to capture electroencephalogram (EEG) from outside the skull while the implantable electrodes are employed to measure electrocorticogram (ECoG), local field potential (LFP) or spike activity. Recent progress in microfabrication technology enables the development of on-board electrode that combines the entire signal processing including amplification, filtering, and digitization. This will contribute to diagnostic and therapeutic application of the neural interface for restoring physical, psychological and social functions by improving motor, sensory or cognitive abilities.

Idle state classification using spiking activity and local field potentials in a brain computer interface.

Previous studies of intracortical brain-computer interfaces (BCIs) have often focused on or compared the use of spiking activity and local field potentials (LFPs) for decoding kinematic movement parameters. Conversely, using these signals to detect the initial intention to use a neuroprosthetic device or not has remained a relatively understudied problem. In this study, we examined the relative performance of spiking activity and LFP signals in detecting discrete state changes in attention regarding a user's desire to actively control a BCI device. Preliminary offline results suggest that the beta and high gamma frequency bands of LFP activity demonstrated a capacity for discriminating idle/active BCI control states equal to or greater than firing rate activity on the same channel. Population classifier models using either signal modality demonstrated an indistinguishably high degree of accuracy in decoding rest periods from active BCI reach periods as well as other portions of active BCI task trials. These results suggest that either signal modality may be used to reliably detect discrete state changes on a fine time scale for the purpose of gating neural prosthetic movements.

Sulforhodamine 101, a widely used astrocyte marker, can induce cortical seizure-like activity at concentrations commonly used

Sulforhodamine 101 (SR101) is a preferential astrocyte marker widely used in 2-photon microscopy experiments. Here we show, that topical loading of two commonly used SR101 concentrations, 100 μM and 250 μM when incubated for 10 min, can induce seizure-like local field potential (LFP) activity in both anaesthetized and awake mouse sensori-motor cortex. This cortical seizure-like activity develops in less than ten minutes following topical loading, and when applied longer, these neuronal discharges reliably evoke contra-lateral hindlimb muscle contractions. Short duration (<1 min) incubation of 100 μM and 250 μM SR101 or application of lower concentrations 25 μM and 50 μM of SR101, incubated for 30 and 20 min, respectively, did not induce abnormal LFP activity in sensori-motor cortex, but did label astrocytes, and may thus be considered more appropriate concentrations for in vivo astrocyte labeling. In addition to label astrocytes SR101 may, at 100 μM and 250 μM, induce abnormal neuronal activity and interfere with cortical circuit activity. SR101 concentration of 50 μM or lower did not induce abnormal neuronal activity. We advocate that, to label astrocytes with SR101, concentrations no higher than 50 μM should be used for in vivo experiments.