Background Activity Of Neurons Research Articles

Simulation of background neuronal activity and noise in human intracranial microwire recordings

BackgroundHuman intracranial microwire recordings allow measurement of neuronal activity in human subjects at a fine temporal and spatial scale. The recorded extracellular potentials represent a mixture of action potentials from nearby neurons, local field potentials, and other noise sources. Signal processing of these recordings is used to separate the activity of putative single neurons from other background and noise. To better understand the separation of single neuron activity, one approach is to simulate the signals produced by neurons firing action potentials combined with background activity and noise. New methodThis paper characterizes the background activity and noise in human intracranial microwire recordings and presents an accurate and efficient method of simulation using an infinite impulse response filter to color white noise. Results and comparisonThis method reproduces the power spectral density of the background activity and noise over a frequency range of 1–5000 Hz and is over 200 times faster than previously used methods. It thus facilitates large scale studies of variation of noise sources, field potentials, and processing parameters. It performs equivalently in terms of spike sorting to simulation using white noise. Another advantage is that the simulated signals are known to arise from a pseudorandom number generator and cannot be the result of detecting simulated background spiking activity. ConclusionsThis approach provides a rapid and accurate method of simulating background noise and neural activity in human intracranial microwire recordings. It is suitable for use in large scale simulations to study spike sorting in this type of recording.

Maternal hyperhomocysteinemia increases seizures susceptibility of neonatal rats

AimsNeonatal seizures are severe pathologies which may result in long-term neurological consequences. High plasma concentrations of homocysteine – hyperhomocysteinemia (hHCy) - are associated with epilepsy. In the present study, we evaluated susceptibility to seizure of neonatal rats with prenatal hHCy. Main methodsPrenatal hHCy was induced by feeding females with a high-methionine diet. Experiments were performed on pups during the first three postnatal weeks. Flurothyl-induced epileptic behavior was assessed according to Racine's scale. Epileptiform activity in the hippocampus was recorded using electrophysiological methods. The balance of excitation/inhibition, functional GABAergic inhibition and GABA reversal potential in hippocampal neurons were analyzed. Key findingsRats with hHCy developed more severe stages of behavioral patterns during flurothyl-induced epilepsy with shorter latency. Electrophysiological recordings demonstrated higher background neuronal activity in rats with hHCy. Seizure-like events triggered by flurothyl (in vivo) or 4-aminopyridine (in vitro) showed shorter latency, higher power and amplitude. An increased glutamate/GABA synaptic ratio was shown in the pyramidal neurons of rats with hHCy and more slices demonstrated excitation by isoguvacine, a selective GABA(A) receptor agonist, during the first and second postnatal weeks. The GABA driving force and the reversal potential of GABA(A) currents were more positive during the second postnatal week for hHCy rats. SignificanceThe higher susceptibility to seizures in rats with prenatal hHCy due to a shift in the balance of excitation/inhibition toward excitation may underlie the clinical evidence about the association of hHCy with an increased risk of epilepsy.

Acute effect of antiseizure drugs on background oscillations in Scn1a A1783V Dravet syndrome mouse model.

Dravet syndrome (Dravet) is a rare and severe form of developmental epileptic encephalopathy. Antiseizure medications (ASMs) for Dravet patients include valproic acid (VA) or clobazam (CLB), with or without stiripentol (STP), while sodium channel blockers like carbamazepine (CBZ) or lamotrigine (LTG) are contraindicated. In addition to their effect on epileptic phenotypes, ASMs were shown to modify the properties of background neuronal activity. Nevertheless, little is known about these background properties alterations in Dravet. Here, utilizing Dravet mice (DS, Scn1a A1783V/WT), we tested the acute effect of several ASMs on background electrocorticography (ECoG) activity and frequency of interictal spikes. Compared to wild-type mice, background ECoG activity in DS mice had lower power and reduced phase coherence, which was not corrected by any of the tested ASMs. However, acute administration of Dravet-recommended drugs, VA, CLB, or a combination of CLB + STP, caused, in most mice, a reduction in the frequency of interictal spikes, alongside an increase in the relative contribution of the beta frequency band. Conversely, CBZ and LTG increased the frequency of interictal spikes, with no effect on background spectral properties. Moreover, we uncovered a correlation between the reduction in interictal spike frequency, the drug-induced effect on the power of background activity, and a spectral shift toward higher frequency bands. Together, these data provide a comprehensive analysis of the effect of selected ASMs on the properties of background neuronal oscillations, and highlight a possible correlation between their effect on epilepsy and background activity.

Low-frequency, low-intensity ultrasound modulates light responsiveness of mouse retinal ganglion cells

Objective. Ultrasound modulates the firing activity of retinal ganglion cells (RGCs), but the effects of lower-frequency, lower-intensity ultrasound on RGCs and underlying mechanism(s) remain poorly understood. This study aims to address these questions. Approach. Multi-electrode recordings were used in this study to record the firing sequences of RGCs in isolated mouse retinas. RGCs’ background firing activities as well as their light responses were recorded with or without ultrasound stimulation. Cross-correlation analyses were performed to investigate the possible cellular/circuitry mechanism(s) underlying ultrasound modulation. Main results. It was found that ultrasound stimulation of isolated mouse retina enhanced the background activity of ON-RGCs and OFF-RGCs. In addition, background ultrasound stimulation shortened the light response latency of both ON-RGCs and OFF-RGCs, while enhancing part of the RGCs’ (both ON- and OFF-subtypes) light response and decreasing that of the others. In some ON-OFF RGCs, the ON- and OFF-responses of an individual cell were oppositely modulated by the ultrasound stimulation, which suggests that ultrasound stimulation does not necessarily exert its effect directly on RGCs, but rather via its influence on other type(s) of cells. By analyzing the cross-correlation between the firing sequences of RGC pairs, it was found that concerted activity occurred during ultrasound stimulation differed from that occurred during light stimulation, in both spatial and temporal aspects. These results suggest that the cellular circuits involved in ultrasound- and light-induced concerted activities are different and glial cells may be involved in the circuit in response to ultrasound. Significance. These findings demonstrate that ultrasound affects neuronal background activity and light responsiveness, which are critical for visual information processing. These results may also imply a hitherto unrecognized role of glial cell activation in the bidirectional modulation effects of RGCs and may be critical for the nervous system.

Hyperhomocysteinemia Increases Cortical Excitability and Aggravates Mechanical Hyperalgesia and Anxiety in a Nitroglycerine-Induced Migraine Model in Rats.

Homocysteine is a sulfur-containing endogenous amino acid leading to neurotoxic effects at high concentrations. Population studies suggest an association between plasma homocysteine levels and the risk of migraine headaches. The aim of this study was to analyze the sensitivity of rats with prenatal hyperhomocysteinemia (hHCY) in respect of the development of behavioral correlates of headache and spreading cortical depolarization (CSD) in a migraine model induced by the administration of the nitric oxide (NO) donor nitroglycerin. Animals with hHCY were characterized by migraine-related symptoms such as mechanical hyperalgesia, high-level anxiety, photophobia, as well as an enhanced level of neuronal activity in the somatosensory cortex along with a lower threshold of CSD generation. Likewise, acute or chronic intermittent administration of nitroglycerin also induced the development of mechanical allodynia, photophobia and anxiety in control groups. However, these symptoms were more pronounced in rats with hHCY. Unlike hHCY, nitroglycerin administration did not affect the threshold of CSD generation, but like hHCY, increased the background neuronal activity in layers 2/3 and 4 of the cerebral cortex. The latter was more pronounced in animals with hHCY. Thus, the migraine profile associated with hHCY can be further exaggerated in conditions with enhanced levels of migraine triggering the gaseous transmitter NO. Our data are consistent with the view that high levels of plasma homocysteine can act as a risk factor for the development of migraine.

SNAP25 Inhibits Glioma Progression by Regulating Synapse Plasticity via GLS-Mediated Glutaminolysis.

BackgroundNeuronal activity regulated by synaptic communication exerts an important role in tumorigenesis and progression in brain tumors. Genes for soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) annotated with the function ‘vesicle’ about synaptic connectivity were identified, and synaptosomal-associated protein 25 (SNAP25), one of those proteins, was found to have discrepant expression levels in neuropathies. However, the specific mechanism and prognostic value of SNAP25 during glioma progression remain unclear.MethodsUsing RNA sequencing data from The Cancer Genome Atlas (TCGA) database, the differential synaptosis-related genes between low grade glioma (LGG) and glioblastoma (GBM) were identified as highly correlated. Cox proportional hazards regression analysis and survival analysis were used to differentiate the outcome of low- and high-risk patients, and the Chinese Glioma Genome Atlas (CGGA) cohort was used for validation of the data set. RT-qPCR, western blot, and immunohistochemistry assays were performed to examine the expression level of SNAP25 in glioma cells and samples. Functional assays were performed to identify the effects of SNAP25 knockdown and overexpression on cell viability, migration, and invasion. Liquid chromatography-high resolution mass spectrometry (LC-MS)-based metabolomics approach was presented for identifying crucial metabolic disturbances in glioma cells. In situ mouse xenograft model was used to investigate the role of SNAP25 in vivo. Then, an immunofluorescence assay of the xenograft tissue was applied to evaluate the expression of the neuronal dendron formation marker-Microtubule Associated Protein 2 (MAP2).ResultsSNAP25 was decreased in level of expression in glioma tissues and cell lines, and low-level SNAP25 indicated an unfavorable prognosis of glioma patients. SNAP25 inhibited cell proliferation, migration, invasion and fostered glutamine metabolism of glioma cells, exerting a tumor suppressor role. Overexpressed SNAP25 exerted a lower expression level of MAP2, indicating poor neuronal plasticity and connectivity. SNAP25 could regulate glutaminase (GLS)-mediated glutaminolysis, and GLS knockdown could rescue the anti-tumor effect of SNAP25 in glioma cells. Moreover, upregulated SNAP25 also decreased tumor volume and prolonged the overall survival (OS) of the xenograft mouse.ConclusionSNAP25, a tumor suppressor inhibited carcinogenesis of glioma via limiting glutamate metabolism by regulating GLS expression, as well as inhibiting dendritic formation, which could be considered as a novel molecular therapeutic target for glioma.

Эффекты электромагнитного излучения миллиметрового диапазона на нейрональную активность спинального ядра тройничного нерва крысы

The study examined the effects of continuous low-intensity electromagnetic millimeter waves (MMW; frequency 40 GHz, power density of 0.04 mW/cm2) on ongoing firing of the spinal trigeminal nucleus (STN) neurons and their responses to the electrical stimulation of the dura mater in neurophysiological experiments on anesthetized rats. It is known that local exposure of MMW to certain areas of the skin can have a systemic therapeutic effect in the treatment of various pathologies. In particular, it concerns the use of MMW to treat headache of different genesis, with migraine being the most common form. The mechanisms of migraine are not clear, but it is known that the STN plays a key role in the migraine pathogenesis, providing the primary processing of pain signals from the cranial vessels as well as the transmission of these signals to overlying brain structures, in particular, to the thalamus. Recently, it has been reported that the frequency-modulated MMW causes short-term inhibitory changes in both the background activity of STN neurons and their responses to electrical stimulation of the dura mater. We assumed that the use of MMW in the unmodulated mode will allow to increase the duration of the MMW inhibitory effect on the background and evoked activity of STN neurons and thereby confirm potential antinociceptive action of MMW in migraine. The results of the present study have showed that the exposure of the STN neurons’ cutaneous receptive fields to unmodulated MMW is accompanied by prolonged cumulative inhibition of both the background activity of these neurons and their dural electrostimulation-evoked responses. The data allow considering these effects as an evindence in favour of potential antimigraine action of a continuous low-intensity MMW. It is proposed that the action can be based on the activation of nervous and immune processes in the skin, which, through a chain of neuronal mechanisms, can lead to a decrease in the excitability of STN neurons involved in the pathogenesis of migraine.

The Effect of Natural Ocean Sound Exposure and Ocean-Side Relaxation on Chronic Tinnitus Patients: A Pilot Study in Korea.

Sound therapy is a treatment modality for tinnitus patients by increasing the background neuronal activity in the auditory system and inducing relative alleviation of the tinnitus. This study was performed to evaluate the efficacy of natural ocean sound exposure and ocean-side relaxation in chronic tinnitus patients. We prospectively enrolled all 18 chronic tinnitus patients (≥6 months) from July to November 2018. All patients completed 90 hours of our programs. The improvement in their subjective tinnitus severity, moods, the quality of life, and sleep was serially assessed using several questionnaires at baseline, immediately, and 1 month after the program. Changes in serum stress hormone levels of the patients were also compared between the baseline and immediately after the program. Average total Tinnitus Handicap Questionnaire score and factor 2 (hearing difficulty related to tinnitus) score significantly improved over time (P = .024 and P = .002). Patient's serum cortisol and epinephrine level did not show significant decrease, and serum norepinephrine and serotonin level significantly increased immediately after our program (P < .001 and P < .001). Natural ocean sound exposure and ocean-side relaxation for short-term period has a potential efficacy on chronic tinnitus patients.

The Fractal Features of the Background Activity of Neurons in the Auditory Center of the Frog Midbrain

Abstract—Statistics were obtained for background firing activity recorded from several neurons of the auditory center of the midbrain (semicircular torus) in the common frog. The methods were those used to analyze the temporal flow of fractal point processes. Most neurons showed a power-law increase in the variance-to-mean ratio (Fano factor) of pulse number with the time window increasing from hundreds of milliseconds to several tens of seconds, although cells whose background firing activity was close to random were also observed. A method based on the registration of local features (the Allan factor as a function of the same time window) confirmed the fractal properties for many cells. A power-law growth of the Allan factor usually began at large time windows. The third method of fractal analysis (the Hurst index) also argued in favor of the randomness and fractality of background firing activity. The relationships with other statistics of random point processes were analyzed for the fractal characteristics. A comparison with data obtained for neurons of the medulla oblongata indicated that the variability of firing activity slight increases along the auditory pathway.

Modeling of Transcranial Magnetic Stimulation Versus Pallidal Deep Brain Stimulation for Parkinson's Disease

Non-invasive repetitive transcranial magnetic stimulation (TMS) is a neuromodulation technique in which time-varying magnetic fields induce electric fields on the patient's brain, thus stimulating neurons in the targeted cortical region. We have created a new model of the basal ganglia motor pathway in the human brain, using the Python package called NEST. We simulated healthy nuclei with random noise and connection weights optimized to mimic established background neuronal activity noise in the connecting nuclei. We then simulated Parkinsonism by removing dopaminergic (DAergic) input from the substantia nigra pars compacta to the striatum. The results showed the production of characteristic Parkinsonian neuronal features, ranging from pathological highly irregular to burst signals matching those found during in vivo animal and human microelectrode recording studies. With the model thus validated, we modeled deep brain stimulation (DBS) current delivery to the globus pallidus internus (GPi) in a Parkinsonian brain and simulated neuron firing as an effect of DBS. Finally, repetitive TMS at various frequencies was simulated at the level of the motor cortex, which produced predicted downstream firing rate effects and intra-neuronal synchrony at the level of the GPi. Although typical clinical TMS at 10 pulses/s was suggested to offer some beneficial effects, firing rates and patterns and desynchronous firing were most effectively normalized to match those seen in a healthy GPi upon stimulation at 50 pulses/s. Thus, our modeling suggests that cortical, non-invasive TMS may be a viable alternative to DBS surgery for patients with Parkinson's disease (PD).

Monocular enucleation alters retinal waves in the surviving eye

BackgroundActivity in neurons drives afferent competition that is critical for the refinement of nascent neural circuits. In ferrets, when an eye is lost in early development, surviving retinogeniculate afferents from the spared eye spread across the thalamus in a manner that is dependent on spontaneous retinal activity. However, how this spontaneous activity, also known as retinal waves, might dynamically regulate afferent terminal targeting remains unknown.MethodsWe recorded retinal waves from retinae ex vivo using multi-electrode arrays. Retinae came from ferrets who were binocular or who had one eye surgically removed at birth. Linear mixed effects models were used to investigate the effects of early monocular enucleation on retinal wave activity.ResultsWhen an eye is removed at birth, spontaneous bursts of action potentials by retinal ganglion cells (RGCs) in the surviving eye are shorter in duration. The shortening of RGC burst duration results in decreased pairwise RGC correlations across the retina and is associated with the retinal wave-dependent spread of retinogeniculate afferents previously reported in enucleates.ConclusionOur findings show that removal of the competing eye modulates retinal waves and could underlie the dynamic regulation of competition-based refinement during retinogeniculate development.

Pyramidal Cell Selective Ablation of N-Methyl-D-Aspartate Receptor 1 Causes Increase in Cellular and Network Excitability

BackgroundNeuronal activity at gamma frequency is impaired in schizophrenia (SZ) and is considered critical for cognitive performance. Such impairments are thought to be due to reduced N-methyl-D-aspartate receptor (NMDAR)-mediated inhibition from parvalbumin interneurons, rather than a direct role of impaired NMDAR signaling on pyramidal neurons. However, recent studies suggest a direct role of pyramidal neurons in regulating gamma oscillations. In particular, a computational model has been proposed in which phasic currents from pyramidal cells could drive synchronized feedback inhibition from interneurons. As such, impairments in pyramidal neuron activity could lead to abnormal gamma oscillations. However, this computational model has not been tested experimentally and the molecular mechanisms underlying pyramidal neuron dysfunction in SZ remain unclear. MethodsIn the present study, we tested the hypothesis that SZ-related phenotypes could arise from reduced NMDAR signaling in pyramidal neurons using forebrain pyramidal neuron specific NMDA receptor 1 knockout mice. ResultsThe mice displayed increased baseline gamma power, as well as sociocognitive impairments. These phenotypes were associated with increased pyramidal cell excitability due to changes in inherent membrane properties. Interestingly, mutant mice showed decreased expression of GIRK2 channels, which has been linked to increased neuronal excitability. ConclusionsOur data demonstrate for the first time that NMDAR hypofunction in pyramidal cells is sufficient to cause electrophysiological, molecular, neuropathological, and behavioral changes related to SZ.

Dynamic modulation of an orientation preference map by GABA responsible for age-related cognitive performance

Accumulating evidence suggests that cognitive declines in old (healthy) animals could arise from depression of intracortical inhibition, for which a decreased ability to produce GABA during senescence might be responsible. By simulating a neural network model of a primary visual cortical (V1) area, we investigated whether and how a lack of GABA affects cognitive performance of the network: detection of the orientation of a visual bar-stimulus. The network was composed of pyramidal (P) cells and GABAergic interneurons such as small (S) and large (L) basket cells. Intrasynaptic GABA-release from presynaptic S or L cells contributed to reducing ongoing-spontaneous (background) neuronal activity in a different manner. Namely, the former exerted feedback (S-to-P) inhibition and reduced the frequency (firing rate) of action potentials evoked in P cells. The latter reduced the number of saliently firing P cells through lateral (L-to-P) inhibition. Non-vesicular GABA-release, presumably from glia and/or neurons, into the extracellular space reduced the both, activating extrasynaptic GABAa receptors and providing P cells with tonic inhibitory currents. By this combinatorial, spatiotemporal inhibitory mechanism, the background activity as noise was significantly reduced, compared to the stimulus-evoked activity as signal, thereby improving signal-to-noise (S/N) ratio. Interestingly, GABA-spillover from the intrasynaptic cleft into the extracellular space was effective for improving orientation selectivity (orientation bias), especially when distractors interfered with detecting the bar-stimulus. These simulation results may provide some insight into how the depression of intracortical inhibition due to a reduction in GABA content in the brain leads to age-related cognitive decline.

Complexity and multifractality of neuronal noise in mouse and human hippocampal epileptiform dynamics

Fractal methods offer an invaluable means of investigating turbulent nonlinearity in non-stationary biomedical recordings from the brain. Here, we investigate properties of complexity (i.e. the correlation dimension, maximum Lyapunov exponent, 1/fγ noise and approximate entropy) and multifractality in background neuronal noise-like activity underlying epileptiform transitions recorded at the intracellular and local network scales from two in vitro models: the whole-intact mouse hippocampus and lesional human hippocampal slices. Our results show evidence for reduced dynamical complexity and multifractal signal features following transition to the ictal epileptiform state. These findings suggest that pathological breakdown in multifractal complexity coincides with loss of signal variability or heterogeneity, consistent with an unhealthy ictal state that is far from the equilibrium of turbulent yet healthy fractal dynamics in the brain. Thus, it appears that background noise-like activity successfully captures complex and multifractal signal features that may, at least in part, be used to classify and identify brain state transitions in the healthy and epileptic brain, offering potential promise for therapeutic neuromodulatory strategies for afflicted patients suffering from epilepsy and other related neurological disorders.

The dynamics of analogue signalling in local networks controlling limb movement

Communication by analogue signals is relatively common in arthropod local networks. In the locust, non-spiking local interneurons play a key role in controlling sets of motor neurons in the generation of local reflex movements of the limbs. Here, our aim was two-fold. Our first aim was to determine the coding properties of a subpopulation of these interneurons by using system identification approaches. To this end, the femoro-tibial chordotonal organ, which monitors the movements of the tibia about the femur, was stimulated with Gaussian white noise and with more natural stimuli corresponding to the movements of the tibia during walking. The results showed that the sample of interneurons analysed displayed a wide, and overlapping, range of response characteristics. The second aim was to develop and test improved data analysis methods for describing neuronal function that are more robust and allow statistical analysis, a need emphasized by the high levels of background neuronal activity usually observed. We found that nonlinear models provided an improved fit in describing the response properties of interneurons that were then classified with statistical clustering methods. We identified four distinct categories of interneuron response that can be further divided into nine groups, with most interneurons being excited during extension movements of the leg, reflecting the outputs of upstream spiking local interneurons.

Heterogeneity and independency of unitary synaptic outputs from hippocampal CA3 pyramidal cells

The variation of individual synaptic transmission impacts the dynamics of complex neural circuits. We performed whole-cell recordings from monosynaptically connected hippocampal neurons in rat organotypic slice cultures using a synapse mapping method. The amplitude of unitary excitatory postsynaptic current (uEPSC) varied from trial to trial and was independent of the physical distance between cell pairs. To investigate the source of the transmission variability, we obtained patch-clamp recordings from intact axons. Axonal action potentials (APs) were reliably transmitted throughout the axonal arbour and showed modest changes in width. In contrast, calcium imaging from presynaptic boutons revealed that the amplitude of AP-evoked calcium transients exhibited large variations both among different boutons at a given trial and among trials in a given bouton. These results suggest that a factor contributing to the uEPSC fluctuations is the variability in calcium dynamics at presynaptic terminals. Finally, we acquired triple whole-cell recordings from divergent circuit motifs with one presynaptic neuron projecting to two postsynaptic neurons. Consistent with the independency of calcium dynamics among axonal boutons, a series of uEPSC fluctuations was not correlated between the two postsynaptic cells, indicating that different synapses even from the same neuron act independently.We conclude that the intra-bouton and inter-bouton variability in AP-induced calcium dynamics determine the heterogeneity and independency of uEPSCs.

Spontaneous firing statistics and information transfer in electroreceptors of paddlefish

We study information processing in a peripheral sensory receptor system which possesses spontaneous dynamics with two distinct rhythms. Such organization was found in the electrosensory system of paddlefish and is represented by two distinct and unidirectionally coupled oscillators, resulting in biperiodic spontaneous firing patterns of sensory neurons. We use computational modeling to elucidate the functional role of spontaneous oscillations in conveying information from sensory periphery to the brain. We show that biperiodic organization resulting in nonrenewal statistics of background neuronal activity leads to significant improvement in information transfer through the system as compared to an equivalent renewal model.

Bilateral changes in excitability of sensorimotor cortices during unilateral movement: Combined electroencephalographic and transcranial magnetic stimulation study

It remains unclear what neuronal mechanisms in humans are reflected in the activation of the ipsilateral hemisphere during the performance of unilateral movements. To address this question we combined transcranial magnetic stimulation (TMS), electroencephalography (EEG), and electromyographic (EMG) recordings of motor evoked potentials (MEPs). Compared with previous TMS studies, where changes in excitability might be related to both cortical and spinal mechanisms, our setup allowed a more direct evaluation of the cortical processes related to the performance of unilateral movements. EEG responses showed that the unilateral motor reactions were associated with the bilateral increase in the excitability of sensorimotor cortices. However, this increase was smaller in the ipsilateral hemisphere most likely due to the fact that the excitation in ipsilateral hemisphere coincided with additional inhibitory processes related to the suppression of mirror movements. This explanation was further corroborated by showing that only contralateral changes in cortical excitability led to the increase in the amplitude of peripheral MEPs, while neuronal activation in the ipsilateral hemisphere was not associated with the changes in the muscle responses. These results suggest that the increased excitability in the ipsilateral hemisphere was uncoupled from the modulation of the cortico-spinal output. Moreover, we show that the background neuronal activity during unilateral movements was different in the ipsi- and contralateral hemisphere. This difference most likely reflects inter-hemispheric balance between the excitation and inhibition which is required for the optimal performance of the unilateral movement.

Background activity of neurons of the supraoptic hypothalamic nucleus in rats under conditions of vibrational stimulation and electromagnetic extrahigh-frequency irradiation

We analyzed background impulse activity of neurons of the supraoptic nucleus of the rat hypothalamus in the course of 15-day-long isolated action of generalized vibrational stimulation and combination of such stimulation with irradiation of the animal’s head with low-intensity extrahigh-frequency (EHF, millimeter-range) electromagmetic waves. The distributions of the neurons by the level of regularity and dynamics of spike trains, separate frequency ranges of impulsation, and pattern of interspike interval (ISI) histograms were estimated. We also calculated the mean frequency of discharges and coefficient of variation of ISIs. A trend toward decreases in the deviations of some parameters of neuronal spike activity generated by supraoptic neurons, which were evident within early time intervals of isolated action of vibration (5 to 10 days), was observed under the influence of EHF electromagnetic irradiation; thus, the latter factor probably exerts a sedative effect.

Effects of cholinergic overstimulation on isoflurane potency and efficacy in cortical and spinal networks

In scenarios of terrorist attacks with organophosphorus compounds it appears likely that medical aid is required by victims not only suffering from the intoxication but also from physical trauma. These subjects may have to undergo surgical interventions, raising the need for anaesthesia. This prompts the question of how anaesthetic agents work in intoxicated patients. Organophosphates block acetylcholinesterase activity, thereby inducing excessive cholinergic overstimulation in the central nervous system. As the neocortex and spinal cord are important substrates for general anaesthetics, we investigated to what extent cholinergic overstimulation affects the potency and efficacy of the commonly used volatile anaesthetic isoflurane in depressing action potential activity of cortical and spinal neurons. We first quantified the effects of isoflurane in the absence of acetylcholine by performing extracellular voltage recordings in cultured tissue slices. Isoflurane induced a concentration-dependent decrease of neuronal activity in neocortical (EC 50 = 0.43 ± 0.08 MAC) and spinal slices (EC 50 = 0.41 ± 0.03 MAC). At concentrations above 1.5 MAC, the anaesthetic almost completely depressed action potential firing in both preparations. Next, we studied the effects of acetylcholine (10 μM) in the absence of isoflurane. Acetylcholine approximately doubled spontaneous activity in neocortical and spinal slices. When applying isoflurane together with acetylcholine, different interactions between these agents were observed in neocortical and spinal networks. Acetylcholine significantly reduced both the potency and efficacy of the anaesthetic in neocortical (efficacy 83%; EC 50 = 1.16 ± 0.02 MAC) but not in spinal (efficacy 100%; EC 50 = 0.41 ± 0.04 MAC) slices. Our results indicate that cholinergic overstimulation increases the requirement for anaesthetic agents in patients suffering from organophosphorus poisoning via enhancing neuronal background activity of neocortical and spinal neurons and in addition via decreasing drug potency and efficacy in the cortex. Raising anaesthetic concentrations into a high-dose range may not be an appropriate alternative to compensate the increased excitability, since high concentrations of anaesthetics may worsen cardiac abnormalities and hemodynamic instability frequently observed in these patients.