Neuronal Electrical Activity Research Articles

Explanation to negative feedback induced-enhancement of neural electronic activities with phase response curve

It has been found in many experimental and theoretical studies that autapse regulates the electrical activities of single neurons and the spatiotemporal behaviors of neuronal networks through feedback or coupling currents to achieve physiological functions. In the present paper, the effect of inhibitory self-feedback on spiking patterns near Hopf bifurcation point is studied in the deterministic Morris-Lecar model and the stochastic Morris-Lecar model, and the dynamical mechanism is acquired with the phase response curve (PRC) of spiking to the inhibitory square pulse current stimulation. The inhibitory self-feedback current with a suitable time-delay can induce the spiking frequency to increase, which is different from the traditional viewpoint that the inhibitory stimulations often induce the firing frequency to decrease. For the remained time delays, spiking frequency decreases. Furthermore, the changes of spiking frequency, induced by the inhibitory self-feedback current, can be well explained with the dynamical responses of the spiking pattern of a single neuron without autapse to an inhibitory square pulse current stimulation. For the spiking pattern of a neuron without autapse, when an inhibitory square pulse stimulation current resembling to the inhibitory self-feedback current is applied at some suitable phases after an action potential/spike, the phase of the action potential/spike following the square pulse current advances, which leads the interspike intervals (<i>ISIs</i>) to decrease and firing frequency to increase. For the remained stimulation phases of the inhibitory pulse current, the response phase of the following action potential/spike delays. Therefore, the PRC of the action potential/spike shows the characteristics of type-II excitability corresponding to Hopf bifurcation. The stimulation phase of the inhibitory square pulse current that can induce the spiking frequency of single neurons to increase corresponds to the time delay of inhibitory self-feedback that can enhance firing frequency, which shows that the type-II PRC is the cause that the inhibitory self-feedback can induce the spiking frequency to increase. Finally, when noise is introduced into the ML model with inhibitory self-feedback, the coefficient of variation (<i>CV</i>) of the <i>ISIs</i> is smaller for the longer time delay of the self-feedback or the stronger coupling strength of the autapse, that is, the spike-timing precision is improved for the smaller <i>CV</i> of <i>ISIs</i>. Such a result is consistent with the experimental result that slow inhibitory autapse can enhance spike-timing precision. The results present a novel phenomenon that negative self-feedback can enhance the response of the system and the corresponding nonlinear dynamical mechanism, i.e. the PRC, provide a new method of regulating the neural electrical activities, and are helpful in understanding the potential function of inhibitory autapse.

Two-pore-domain potassium channels and molecular mechanisms underlying migraine

Migraine is a common, disabling neurological disorder with genetic, environmental and hormonal components and a prevalence estimated at ∼15%. Migraine episodes are notably related, among several factors, to electric hyperexcitability in sensory neurons. Their electrical activity is controlled by ion channels that generate current, specifically by the two-pore-domain potassium, K2P, channels, which inhibit electrical activity. Mutation in the gene encoding TRESK, a K2P channel, causes the formation of TRESK-MT1, the expected non-functional C-terminal truncated TRESK channel, and an additional unexpected protein, TRESK-MT2, which corresponds to a non-functional N-terminal truncated TRESK channel, through a mechanism called frameshift mutation-induced Alternative Translation Initiation (fsATI). TRESK-MT1 is inactive but TRESK-M2 targets two other ion channels, TREK1 and TREK2, inducing a great stimulation of the neuronal electrical activity that may cause migraines. These findings identify TREK1 and TREK2 as potential molecular targets for migraine treatment and suggest that fsATI should be considered as a distinct class of mutations.

Orexin type-2 receptor blockade prevents the nicotine-induced excitation of nucleus accumbens core neurons in rats: An electrophysiological perspective.

The nucleus accumbens core (NAcc) expresses both orexin and nicotinic acetylcholine receptors (nAChRs). Orexin is among important neurotransmitters, which regulates addictive properties of drugs of abuse including nicotine. The role of orexin-2 receptor (OX2R) in the regulation of NAcc neural activity in response to nicotine has not yet been studied. Hence, in this study, we examined whether the OX2R antagonist (TCS-OX2-29) can adjust the effects of nicotine on electrical activity of NAcc neurons, in urethane-anesthetized rats, using the single unit recording. Neuronal firing of NAcc was recorded for 15 min, then TCS-OX2-29 (OX2R-antagonist; 1, 3 and 10 ng/rat) or DMSO were microinjected into NAcc, just 5 min before subcutaneous (sc) administration of nicotine (0.5 mg/kg) or saline. The spontaneous firing activity was recorded for 70 min, after nicotine injection. The results demonstrated that nicotine significantly excites the NAcc neurons and interestingly, the administration of TCS-OX2-29 (3 and 10 ng/rat) into the NAcc, inhibited nicotine-induced increases of NAcc neuronal responses. Furthermore, administration of TCS-OX2-29 (10 ng/rat), just 5 min before sc administration of saline instead of nicotine, did not significantly alter the neuronal responses, compared to the saline-control group. Our results showed that, although OX2R blockade alone did not affect neuronal activity in the NAcc, it was able to prevent the exciting effects of nicotine on NAcc neuronal activity. Therefore, we proposed that orexin has a potential modulator effect, in response to nicotine.

Characterization of Dmrt3-Derived Neurons Suggest a Role within Locomotor Circuits.

Neuronal networks within the spinal cord, collectively known as the central pattern generator (CPG), coordinate rhythmic movements underlying locomotion. The transcription factor doublesex and mab-3-related transcription factor 3 (DMRT3) is involved in the differentiation of the dorsal interneuron 6 class of spinal cord interneurons. In horses, a non-sense mutation in the Dmrt3 gene has major effects on gaiting ability, whereas mice lacking the Dmrt3 gene display impaired locomotor activity. Although the Dmrt3 gene is necessary for normal spinal network formation and function in mice, a direct role for Dmrt3-derived neurons in locomotor-related activities has not been demonstrated. Here we present the characteristics of the Dmrt3-derived spinal cord interneurons. Using transgenic mice of both sexes, we characterized interneurons labeled by their expression of Cre driven by the endogenous Dmrt3 promoter. We used molecular, retrograde tracing and electrophysiological techniques to examine the anatomical, morphological, and electrical properties of the Dmrt3-Cre neurons. We demonstrate that inhibitory Dmrt3-Cre neurons receive extensive synaptic inputs, innervate surrounding CPG neurons, intrinsically regulate CPG neuron's electrical activity, and are rhythmically active during fictive locomotion, bursting at frequencies independent to the ventral root output. The present study provides novel insights on the character of spinal Dmrt3-derived neurons, data demonstrating that these neurons participate in locomotor coordination.SIGNIFICANCE STATEMENT In this work, we provide evidence for a role of the Dmrt3 interneurons in spinal cord locomotor circuits as well as molecular and functional insights on the cellular and microcircuit level of the Dmrt3-expressing neurons in the spinal cord. Dmrt3 neurons provide the first example of an interneuron population displaying different oscillation frequencies. This study presents novel findings on an under-reported population of spinal cord neurons, which will aid in deciphering the locomotor network and will facilitate the design and development of therapeutics for spinal cord injury and motor disorders.

Neuronal firing and DNA dynamics in a neural network

We study the mutual effects of neuronal electrical activity and DNA dynamics in a network of electrically coupled neurons with nearest neighbors communication. For that we develop by means of the coupling function method, a mathematical DNA-neuron model that can be considered as an extension of the simplified Hodgkin-Huxley models. Numerically, we explore the biological properties of the model with emphasis on local phase transitions and synchronous neural activity. Our results suggest that firing and coherent behavior of neural network are controlled by DNA dynamics. Conversely, neuronal activity induces DNA electrochemical denaturation. As a result, we expect that the prominent DNA-neuron model would be worth in controlling gene expression and neurodegenerative diseases in the sensory thalamus.

Childhood-Onset Schizophrenia: Insights from Induced Pluripotent Stem Cells.

Childhood-onset schizophrenia (COS) is a rare psychiatric disorder characterized by earlier onset, more severe course, and poorer outcome relative to adult-onset schizophrenia (AOS). Even though, clinical, neuroimaging, and genetic studies support that COS is continuous to AOS. Early neurodevelopmental deviations in COS are thought to be significantly mediated through poorly understood genetic risk factors that may also predispose to long-term outcome. In this review, we discuss findings from induced pluripotent stem cells (iPSCs) that allow the generation of disease-relevant cell types from early brain development. Because iPSCs capture each donor’s genotype, case/control studies can uncover molecular and cellular underpinnings of COS. Indeed, recent studies identified alterations in neural progenitor and neuronal cell function, comprising dendrites, synapses, electrical activity, glutamate signaling, and miRNA expression. Interestingly, transcriptional signatures of iPSC-derived cells from patients with COS showed concordance with postmortem brain samples from SCZ, indicating that changes in vitro may recapitulate changes from the diseased brain. Considering this progress, we discuss also current caveats from the field of iPSC-based disease modeling and how to proceed from basic studies to improved diagnosis and treatment of COS.

Exercise training normalizes elevated firing rate of hypothalamic presympathetic neurons in heart failure rats.

Exercise training (ExT) normalizes elevated sympathetic nerve activity in heart failure (HF), but the underlying mechanisms are not well understood. In this study, we examined the effects of 3 wk of ExT on the electrical activity of the hypothalamic presympathetic neurons in the brain slice of HF rats. HF rats were prepared by ligating the left descending coronary artery. The electrophysiological properties of paraventricular nucleus neurons projecting to the rostral ventrolateral medulla (PVN-RVLM) were examined using the slice patch-clamp technique. The neuronal firing rate was elevated in HF rats, and ExT induced a reduction in the firing rate ( P < 0.01). This ExT-induced decrease in the firing rate was associated with an increased frequency of spontaneous and miniature inhibitory postsynaptic current (IPSCs; P < 0.05). There was no significant change in excitatory postsynaptic current. Replacing Ca2+ with Mg2+ in the recording solution reduced the elevated IPSC frequency in HF rats with ExT ( P < 0.01) but not in those without ExT, indicating an increase in the probability of GABA release. In contrast, ExT did not restore the reduced GABAA receptor-mediated tonic inhibitory current in HF rats. A GABAA receptor blocker (bicuculline, 20 μM) increased the firing rate in HF rats with ExT ( P < 0.01) but not in those without ExT. Collectively, these results show that ExT normalized the elevated firing activity by increasing synaptic GABA release in PVN-RVLM neurons in HF rats. Our findings provide a brain mechanism underlying the beneficial effects of ExT in HF, which may shed light on the pathophysiology of other diseases accompanied by sympathetic hyperactivation.

Two Forms of Electrical Transmission Between Neurons.

Electrical signaling is a cardinal feature of the nervous system and endows it with the capability of quickly reacting to changes in the environment. Although synaptic communication between nerve cells is perceived to be mainly chemically mediated, electrical synaptic interactions also occur. Two different strategies are responsible for electrical communication between neurons. One is the consequence of low resistance intercellular pathways, called “gap junctions”, for the spread of electrical currents between the interior of two cells. The second occurs in the absence of cell-to-cell contacts and is a consequence of the extracellular electrical fields generated by the electrical activity of neurons. Here, we place present notions about electrical transmission in a historical perspective and contrast the contributions of the two different forms of electrical communication to brain function.

Model electrical activity of neuron under electric field

Continuous pump and transmission of charges such as calcium, potassium, sodium in the cell can induce time-varying electromagnetic field, and the induced electric field can further modulate the propagation of ions in the cell. Based on the physical laws of static electric field, the effect of electric field in isolate neuron is investigated by introducing additive variable E on the model. Each neuron is considered as a charged body with complex distribution of charges, and electric field is triggered to receive and give response to external electric field and electric stimulus. That is, the electric field is considered as a new variable to describe the polarization modulation of media resulting from external electric field and intrinsic change of density distribution in charges or ions. The dynamical behaviors in electrical activities are analyzed and discussed in the new neuron model, and it confirms that electric field can cause distinct mode transition in electrical activities of neuron exposed to different kinds of electric field. It could provide new insights to understand signal encoding and propagation in nervous system. Finally, it also suggests that new model can be used for signal propagation between neurons when synapse coupling is suppressed.

Anthelmintic drug actions in resistant and susceptible C. elegans revealed by electrophysiological recordings in a multichannel microfluidic device

Many anthelmintic drugs used to treat parasitic nematode infections target proteins that regulate electrical activity of neurons and muscles: ion channels (ICs) and neurotransmitter receptors (NTRs). Perturbation of IC/NTR function disrupts worm behavior and can lead to paralysis, starvation, immune attack and expulsion. Limitations of current anthelmintics include a limited spectrum of activity across species and the threat of drug resistance, highlighting the need for new drugs for human and veterinary medicine. Although ICs/NTRs are valuable anthelmintic targets, electrophysiological recordings are not commonly included in drug development pipelines. We designed a medium-throughput platform for recording electropharyngeograms (EPGs)—the electrical signals emitted by muscles and neurons of the pharynx during pharyngeal pumping (feeding)—in Caenorhabditis elegans and parasitic nematodes. The current study in C. elegans expands previous work in several ways. Detecting anthelmintic bioactivity in drugs, compounds or natural products requires robust, sustained pharyngeal pumping under baseline conditions. We generated concentration-response curves for stimulating pumping by perfusing 8-channel microfluidic devices (chips) with the neuromodulator serotonin, or with E. coli bacteria (C. elegans’ food in the laboratory). Worm orientation in the chip (head-first vs. tail-first) affected the response to E. coli but not to serotonin. Using a panel of anthelmintics—ivermectin, levamisole and piperazine—targeting different ICs/NTRs, we determined the effects of concentration and treatment duration on EPG activity, and successfully distinguished control (N2) and drug-resistant worms (avr-14; avr-15; glc-1, unc-38 and unc-49). EPG recordings detected anthelmintic activity of drugs that target ICs/NTRs located in the pharynx as well as at extra-pharyngeal sites. A bus-8 mutant with enhanced permeability was more sensitive than controls to drug treatment. These results provide a useful framework for investigators who would like to more easily incorporate electrophysiology as a routine component of their anthelmintic research workflow.

Nanowire based bioprobes for electrical monitoring of electrogenic cells

The continuous miniaturization of electronic components and the emergence of nano-biotechnology has opened new perspectives to monitor electrical activities at the single cell level. Here, we describe the creation of very high surface-to-volume ratio passive devices (vertical nanowire probes) using large-scale fabrication process, allowing to follow the electrical activity of mammalian neurons. Based on conventional silicon processing, the silicon nanowires were silicided in platinum in order to improve their electrochemical performances and to guarantee their biocompatibility. Very high signal to noise ratio was achieved (up to 2000) when measuring spontaneous action potentials. Moreover, this bio-platform was used to record the impact of various bio-chemical and electrical stimulations on neuronal activity. To conclude, this study proposes a thorough comparison of the characteristics and performances of these new nanowire-based nanoprobes with the main alternative systems published up to now.

Neuronal extracellular microRNAs miR-124 and miR-9 mediate cell-cell communication between neurons and microglia.

In contrast to peripheral macrophages, microglia in the central nervous system (CNS) exhibit a specific deactivated phenotype; however, it is not clear how this phenotype is maintained. Two alternative hypotheses were postulated recently: (a) microglia differ from peripheral macrophages being derived from the yolk sac (YS), whereas peripheral macrophages originate from bone marrow (BM); (b) microglia acquire a specific phenotype under the influence of the CNS microenvironment. We have previously shown that microglia express miR‐124, which was also induced in BM‐derived macrophages co‐cultured with a neurons. We here investigated the possibility of horizontal transfer of the neuron‐specific microRNAs miR‐124 and miR‐9 from primary neurons to microglia/macrophages. We found that after incubation with neuronal conditioned media (NCM), macrophages downregulated activation markers MHC class II and CD45. Neither cultured adult microglia nor YS‐ and BM‐derived macrophages demonstrated intrinsic levels of miR‐124 expression. However, after incubation with NCM, miR‐124 was induced in both YS‐ and BM‐derived macrophages. Biochemical analysis demonstrated that the NCM contained miR‐124 and miR‐9 in complex with small proteins, large high‐density lipoproteins (HDLs), and exosomes. MiR‐124 and miR‐9 were promptly released from neurons, and this process was inhibited by tetrodotoxin, indicating an important role of neuronal electric activity in secretion of these microRNAs. Incubation of macrophages with exogenous miR‐124 resulted in efficient translocation of miR‐124 into the cytoplasm. This study demonstrates an important role of neuronal miRNAs in communication of neurons with microglia, which favors the hypothesis that microglia acquire a specific phenotype under the influence of the CNS microenvironment.

Chronic methylphenidate treatment during adolescence has long-term effects on monoaminergic function.

Psychostimulants like methylphenidate or D-amphetamine are often prescribed for attention deficit and hyperactivity disorders in children. Whether such drugs can be administered into a developing brain without consequences in adulthood is still an open question. Here, using in vivo extracellular electrophysiology in anesthetised preparations, combined with behavioural assays, we have examined the long-term consequences in adulthood of a chronic methylphenidate oral administration (5 mg/kg/day, 15 days) in early adolescent (post-natal day 28) and late adolescent (post-natal day 42) rats, by evaluating body weight change, sucrose preference (indicator of anhedonia), locomotor sensitivity to D-amphetamine and electrical activities of ventral tegmental area dopamine and dorsal raphe nucleus serotonin neurons. Chronic methylphenidate treatment during early or late adolescence did not induce weight deficiencies and anhedonia-like behaviours at adulthood. However, it increased bursting activities of dorsal raphe nucleus serotonin neurons. Furthermore, chronic methylphenidate treatment during early but not during late adolescence enhanced D-amphetamine-induced rearing activity, as well as ventral tegmental area dopamine cell excitability (firing, burst and population activity), associated with a partial desensitisation of dopamine D2 auto-receptors. We have demonstrated here that early, but not late, adolescent exposure to oral methylphenidate may induce long-lasting effects on monoamine neurotransmission. The possible clinical implication of these data will be discussed.

PO-147 Effect of Exercise-induced Fatigue on the Electrical Activity of the External Globus Pallidus Neurons in rats

Objective The motor cortex (MC) stimulation-induced unitary responses of globus pallidus external segment (GPe) neurons in control and exercise induced-fatigue rats were recorded in vivo to examine the role of cortical-striatum-external globus pallidal pathway in the mechanism of central fatigue.&#x0D; Methods 32 Clean healthy male Wistar rats (260~300g), were randomly divided into 4 groups: control group (Control), 1-day fatigue group (1FG), 3-day fatigue group (3FG) and 7-day fatigue group (7FG). Rats were subjected to a 5-day adaptive treadmill training. Modified Bedford treadmill exercise with progressively increasing load was used to creat the exercise fatigue model. （3 levels:8.2 m/min, 15 min; 15m/min, 15 min; 20 m/min, lasting till exhaustion） The spontaneous unit activity and responses to MC stimulation of GPe neurons were recorded by the electrophysiological technique of extracellular recording of glass microelectrodes.&#x0D; Results The results showed that the firing frequency of high-frequency firing with pause (HFP) and low frequency firing with burst (LFB) in the GPe of 1FG was comparable with that of control group (P&gt;0.05). However in 3FG and 7FG , the percentage of HFP neuron was significantly decreased (P&lt;0.05), while the proportion of LFB was significantly increased (P&lt;0.05), and the average firing rate of LFB was higher and inter spike intervals (ISI) was significantly lower than that of the control group. With 200μA electrical stimulation, the explosive discharge of GPe neurons was attenuated after fatigue in rats. The response of GPe neurons to variable frequency stimulation in exhausted model groups was stronger than that of the control group.MC-stimulation typically induced a triphasic response composed of early excitation, inhibition, and late excitation in GPe neurons. The population of neurons showing a short inhibition slightly increased in 3FG and 7FG.&#x0D; Conclusions 1. The results confirmed that GPe is an important nucleus of basal ganglia involved in the regulation of exercise-induced fatigue by the change of spontaneous activity.&#x0D; &#x0D; Electrical stimulation on the cortex can alter response patterns of GPe neurons in exercise-induced fatigue rats, the results confirmed that the Ctx-Str-GPe neural pathway is involved in the regulation of exercise fatigue, and the indirect pathway is over-activated.&#x0D;

Autaptic modulation-induced neuronal electrical activities and wave propagation on network under electromagnetic induction

Based on an improved HR neuron model, the effects of electrical and chemical autapses on the firing activities of single neurons are studied, and the wave propagation in forward feedback neural network is also discussed by considering autapstic regulation under different intensities of electromagnetic induction. It is found that the electrical activities of single neuron can be changed by exerting excitatory or inhibitory of electrical and chemical autapses. With different feedback gains of electromagnetic induction current, membrane potential shows the oscillatory solutions and steady states. Under the condition of different autapse or electromagnetic induction, the propagation of electrical activities caused by the central neuron is transformed in the forward feedback network. Moreover, the spatial synchronization of the network will be changed by choosing different coupling intensities and feedback gains. It is proved that the electrical and chemical autapses play a significant role in firing modes of single neuron and the wave propagation of the forward feedback networks under the electromagnetic induction.

Effects of temperature and electromagnetic induction on action potential of Hodgkin–Huxley model

Based on an improved the Hodgkin–Huxley (HH) neuron model which is driven by the electromagnetic induction, the effects of temperature and electromagnetic induction on the action potential of neuron are investigated by numerical computations. It is very interesting that, under the fixed condition of electromagnetic induction, there is a region for the electrical activity of neuron in the external current and temperature parameters plane, the region of electrical firing is similar to the Arnold’ tongue-like structure, and the Arnold’ tongue originates from the nonlinear variation of temperature with the increasing of threshold external current. The effects of temperature and electromagnetic induction on neuronic electrical activity are respectively discussed by using numerical simulations. Our results provide new insights into the roles of temperature in the improved HH neuron model, the existence of Arnold’ tongue-like structure might give some insights for the treatment of neurological diseases such as the epilepsia.

PL - 022 Effects of exercise-induced fatigue on autonomic activity and dopamine metabolism in rats after D2DR modulation

Objective Objective: After injection of D2DR antagonist and agonist, the autonomic activity and striatal neurons electrical activity of rats with exercise-induced fatigue were recorded to explore the role of DA receptors in the central mechanism of exercise-induced fatigue.&#x0D; Methods Methods: Used male Wistar rats, randomly divided into 7 groups: control group (CG), one-time exhaustive exercise group (1FG), 3D repetitive exhaust group (3FG), and 7D repetitive exhaustion group (7FG), 7D repeated exhaustive 24h recovery group (24RG) and 7D repeated exhaustive 48h recovery group (48RG). After 1 week adaptive training in rats, rats attend 7D exhaustive treadmill exercise. Subsequently, the autonomic activity changes of each group with D2DR antagonists and agonists were observed in open filed. Used glass microelectrode extracellular recording technique to observe the dorsolateral striatum neurons change of the rats injected with D2DR antagonist spiperone. Real-time PCR (RT-PCR) molecular biology methods were used to measure the expression of D1DR and D2DR in the striatum after exercise-induced fatigue. To investigate the role of DA neurotransmitter and receptor on central mechanism of exercise-induced fatigue.&#x0D; Results Results: (1) With the increase of treadmill exercise load, the total distance of each group became shorter, and the recovery phase gradually recovered to a quiet level. The maximum exercise speed of rats in 7FG was significantly higher than 1FG (P&lt;0.05).The average exercise speed of rats in each group was significantly lower than CG (P&lt;0.05).The average speed of 7FG and 24RG were significantly lower than 1FG(P&lt;0.05). the average movement speed of the 48RG was higher than 7FG;(2) After D2DR antagonist injection, the exhaustive time of rats was significantly lower than CG(P&lt;0.01), while the exhaustive time of D2DR agonist intervention was significantly increased (P&lt;0.01).The active areas of the rats in the open field were concentrated in the corners and margins. The distance of normal rats in 60 min was about 159 m. The activity of rats decreased after D2DR antagonist intervention, the movement distance of rats in CG、1FG and 48RG were significant reduced;(3) After injection of D2DR antagonist, The excitability of dorsolateral striatum neurons were affected by 56.10%, 9.76% (4/41) increased excitability, and 46.34% (19/41) decreased, the inhibitory effect of D2DR agonist was higher than excitatory effects (P&lt;0.05);(4) RT-PCR data showed that there was no significant change in the expression of D1DR in the striatum after exercise-induced fatigue, and D2DR was significantly higher than the CG (P&lt;0.01).&#x0D; Conclusions Conclusion:(1) With the increase of fatigue in rats, the total distance of exercise in each group gradually decreased;(2) Exercise-induced fatigue affects the expression of DA receptors in the striatum;(3) D2DR antagonists and agonists can affect the locomotor ability of rats;(4) D2DR antagonist can inhibit striatal neurons in rats with exercise-induced fatigue, suggesting that D2DR may be one of the drug intervention targets of exercise-induced fatigue.(NSFC: 31401018, SKXJX: 2014014).

Novel Method of Non-contact Remote Measurement of Neuronal Electrical Activity.

Measuring the electrical potential of a neuron cell currently requires direct contact with the cell surface. This method requires invasive probing and is limited by the deflection of electricity from baseline. From a clinical perspective, the electrical potential of the brain's surface can only be measured to a depth of one centimeter using an electroencephalogram (EEG), however, it cannot measure much deeper structures. In this trial, we attempt a novel method to remotely record the electromagnetic field (EMF) of action potential provoked from hippocampal neurons without contact.A bipolar stimulating electrode was placed in contact with the CA1 region of viable hippocampal slice from donor mice. The specimen was bathed in artifical cerebrospinal fluid (aCSF) to simulate in vivo conditions. This setup was then placed into a magnetic shielded tube. Very low-frequency EMF sensors were used to obtain recordings. The impedance of the aCSF and hippocampal slice were measured after each stimulation individually and in combination.An electromagnetic signal was detected in three out of four scenarios: (a) aCSF alone with electrical stimulus without a hippocampal slice, (b) Hippocampal slice in aCSF without electrical stimulus and, (c) Hippocampal slice in aCSF with an electric stimulus applied. Therefore, our trial suggests that EMFs from neuronal tissue can be recorded through non-invasive non-contact sensors.

Re-expression of voltage-gated sodium channel subtype Nav1.3 in the substantia nigra after dopamine depletion

Abnormal synchronized oscillatory bursts occurring in the basal ganglia (BG) are suggested to be correlated with motor symptoms in Parkinson’s disease (PD) patients and animal models of PD. Voltage-gated sodium channels (VGSCs) have been demonstrated to play an important role in the abnormal electrical activity of neurons in the BG. Nav1.3, a VGSCs subtype, is predominantly expressed in embryonic and neonatal nervous system but barely detected in the normal adult nervous system in rodents. Here we investigated the expression patterns of Nav1.3 in the BG of 6-OHDA lesioned Sprague Dawley rats. The results showed that Nav1.3 at mRNA and protein levels was abundantly re-expressed in the ipsilateral and contralateral SN at 49 days postlesion, but was rarely detected in the other nuclei of the BG in the 6-OHDA lesioned rats. Furthermore, Nav1.3 was not only expressed in TH-positive dopaminergic neurons of the ipsilateral and contralateral SN, but also in nestin-positive neural progenitor cells surrounding the ipsilateral SN and the midline region adjacent to the ipsilateral SN in the midbrain at 49 days postlesion. These results suggested that the re-expression of Nav1.3 may influence the electrical activity of dopaminergic neurons in the SN in 6-OHDA lesioned rats.

Agmatine modulates spontaneous activity in neurons of the rat medial habenular complex\u2014a relevant mechanism in the pathophysiology and treatment of depression?

The dorsal diencephalic conduction system connects limbic forebrain structures to monaminergic mesencephalic nuclei via a distinct relay station, the habenular complexes. Both habenular nuclei, the lateral as well as the medial nucleus, are considered to play a prominent role in mental disorders like major depression. Herein, we investigate the effect of the polyamine agmatine on the electrical activity of neurons within the medial habenula in rat. We present evidence that agmatine strongly decreases spontaneous action potential firing of medial habenular neurons by activating I1-type imidazoline receptors. Additionally, we compare the expression patterns of agmatinase, an enzyme capable of inactivating agmatine, in rat and human habenula. In the medial habenula of both species, agmatinase is similarly distributed and observed in neurons and, in particular, in distinct neuropil areas. The putative relevance of these findings in the context of depression is discussed. It is concluded that increased activity of the agmatinergic system in the medial habenula may strengthen midbrain dopaminergic activity. Consequently, the habenular–interpeduncular axis may be dysregulated in patients with major depression.