Electrophysiological Experiments Research Articles

A selection and targeting framework of cortical locations for line-scanning fMRI.

Depth-resolved functional magnetic resonance imaging (fMRI) is an emerging field growing in popularity given the potential of separating signals from different computational processes in cerebral cortex. Conventional acquisition schemes suffer from low spatial and temporal resolutions. Line-scanning methods allow depth-resolved fMRI by sacrificing spatial coverage to sample blood oxygenated level-dependent (BOLD) responses at ultra-high temporal and spatial resolution. For neuroscience applications, it is critical to be able to place the line accurately to (1) sample the right neural population and (2) target that neural population with tailored stimuli or tasks. To this end, we devised a multi-session framework where a target cortical location is selected based on anatomical and functional properties. The line is then positioned according to this information in a separate second session, and we tailor the experiment to focus on the target location. Anatomically, the precision of the line placement was confirmed by projecting a nominal representation of the acquired line back onto the surface. Functional estimates of neural selectivities in the line, as quantified by a visual population-receptive field model, resembled the target selectivities well for most subjects. This functional precision was quantified in detail by estimating the distance between the visual field location of the targeted vertex and the location in visual cortex (V1) that most closely resembled the line-scanning estimates; this distance was on average ~5.5 mm. Given the dimensions of the line, differences in acquisition, session, and stimulus design, this validates that line-scanning can be used to probe local neural sensitivities across sessions. In summary, we present an accurate framework for line-scanning MRI; we believe such a framework is required to harness the full potential of line-scanning and maximize its utility. Furthermore, this approach bridges canonical fMRI experiments with electrophysiological experiments, which in turn allows novel avenues for studying human physiology non-invasively.

Adverse cardiovascular effects of long-term exposure to diethyl phthalate in the rat aorta

Phthalates are classified as priority environmental pollutants, since they are ubiquitous in the environment, have endocrine disrupting properties and can contribute to impaired health. Used primarily in personal care products and excipients for pharmaceuticals, diethyl phthalate (DEP) is a short-chain alkyl phthalate that has been linked to decreased blood pressure, glucose tolerance, and increased gestational weight gain in humans, while in animals it has been associated with atherosclerosis and metabolic syndrome. Although all these findings are related to risk factors or cardiovascular diseases, DEP's vascular impacts still need to be clarified. Thus, performing ex vivo and in vitro experiments, we aimed to understand the vascular DEP effects in rat. To evaluate the vascular contractility of rat aorta exposed to different doses of DEP (0.001–1000 μM), an organs bath was used; and resorting to a cell line of the rat aorta vascular smooth muscle, electrophysiology experiments were performed to analyse the effects of a rapid (within minutes with no genomic effects) and a long-term (24 h with genomic effects) exposure of DEP on the L-type Ca2+ current (ICa,L), and the expression of several genes related with the vascular function. For the first time, vascular electrophysiological properties of an EDC were analysed after a long-term genomic exposure. The results show a hormetic response of DEP, inducing a Ca2+ current inhibition of the rat aorta, which may be responsible for impaired cardiovascular electrical health. Thus, these findings contribute to a greater scientific knowledge about DEP's effects in the cardiovascular system, specifically its implications in the development of electrical disturbances like arrhythmias and its possible mechanisms.

Sex differences in pre- and post-synaptic glutamate signaling in the nucleus accumbens core

BackgroundGlutamate signaling within the nucleus accumbens underlies motivated behavior and is involved in psychiatric disease. Although behavioral sex differences in these processes are well-established, the neural mechanisms driving these differences are largely unexplored. In these studies, we examine potential sex differences in synaptic plasticity and excitatory transmission within the nucleus accumbens core. Further understanding of baseline sex differences in reward circuitry will shed light on potential mechanisms driving behavioral differences in motivated behavior and psychiatric disease.MethodsBehaviorally naïve adult male and female Long-Evans rats, C57Bl/6J mice, and constitutive PKMζ knockout mice were killed and tissue containing the nucleus accumbens core was collected for ex vivo slice electrophysiology experiments. Electrophysiology recordings examined baseline sex differences in synaptic plasticity and transmission within this region and the potential role of PKMζ in long-term depression.ResultsWithin the nucleus accumbens core, both female mice and rats exhibit higher AMPA/NMDA ratios compared to male animals. Further, female mice have a larger readily releasable pool of glutamate and lower release probability compared to male mice. No significant sex differences were detected in spontaneous excitatory postsynaptic current amplitude or frequency. Finally, the threshold for induction of long-term depression was lower for male animals than females, an effect that appears to be mediated, in part, by PKMζ.ConclusionsWe conclude that there are baseline sex differences in synaptic plasticity and excitatory transmission in the nucleus accumbens core. Our data suggest there are sex differences at multiple levels in this region that should be considered in the development of pharmacotherapies to treat psychiatric illnesses such as depression and substance use disorder.

Increased expression of Nav1.6 of reactive astrocytes in the globus pallidus is closely associated with motor deficits in a model of Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disease in elderly people, which is characterized by motor disabilities in PD patients. Nav1.6 is the most abundant subtype of voltage-gated sodium channels (VGSCs) in the brain of adult mammals and rodents. Here we investigated the role of Nav1.6 in the external globus pallidus (GP) involved in the pathogenesis of motor deficits in unilateral 6-OHDA(6-hydroxydopamine)lesioned rats. The results show that Nav1.6 is dramatically increased in reactive astrocytes of the ipsilateral GP in the middle stage, but not different from the control rats in the later stage of the pathological process in 6-OHDA lesioned rats. Furthermore, the down-regulation of Nav1.6 expression in the ipsilateral GP can significantly improve motor deficits in 6-OHDA lesioned rats in the middle stage of the pathological process. The electrophysiological experiments show that the down-regulation of Nav1.6 expression in the ipsilateral GP significantly decreases the abnormal high synchronization between the ipsilateral M1 (the primary motor cortex) and GP in 6-OHDA lesioned rats. Ca2+ imaging reveals that the down-regulation of Nav1.6 expression reduces the intracellular concentration of Ca2+ ([Ca2+ ]i) in primary cultured astrocytes. These findings suggest that the increased Nav1.6 expression of reactive astrocytes in the GP play an important role in the pathogenesis of motor dysfunction in the middle stage in 6-OHDA lesioned rats, which may participate in astrocyte-neuron communication by regulating [Ca2+ ]i of astrocytes, thereby contributing to the formation of abnormal electrical signals of the basal ganglia (BG) in 6-OHDA lesioned rats.

Chronic Pb Exposure Induces Anxiety and Depression-like Behaviors in Mice via Excitatory Neuronal Hyperexcitability in Ventral Hippocampal Dentate Gyrus.

Lead (Pb) is a widespread neurotoxic pollutant. Pb exposure is associated with mood disorders, with no well-established neural mechanisms elucidated. In the present study, we aimed to investigate whether excitatory neurons in the dentate gyrus subregion of the ventral hippocampus (vDG) played a key role in Pb-induced anxiety and depression-like behaviors. C57BL/6 mice were exposed to 100 ppm Pb starting on day 1 of pregnancy until experiments were performed using the offspring. Behavioral studies suggested that chronic Pb exposure triggered anxiety and depression-like behaviors. A combination of electrophysiological, optogenetic, and immunohistochemistry experiments was conducted. Results showed that Pb exposure resulted in excitatory neuronal hyperexcitability in vDG and that the behavioral deficits caused by Pb exposure could be rescued by inhibition of excitatory neuronal activity. Moreover, it was found that the action potential (AP) threshold of excitatory neurons was decreased by electrophysiological recordings. Our study demonstrates a significant role for excitatory neurons in vDG in Pb-induced anxiety and depression-like behaviors in mice, which is likely a result of decreased AP threshold. These outcomes can serve as an important basis for understanding mechanisms of anxiety and depression under environmental Pb exposure and help in the design of therapeutic strategies.

The Complex Proteolipidic Behavior of the SARS-CoV-2 Envelope Protein Channel: Weak Selectivity and Heterogeneous Oligomerization.

The envelope (E) protein is a small polypeptide that can form ion channels in coronaviruses. In SARS coronavirus 2 (SARS-CoV-2), the agent that caused the recent COVID-19 pandemic, and its predecessor SARS-CoV-1, E protein is found in the endoplasmic reticulum-Golgi intermediate compartment (ERGIC), where virion budding takes place. Several reports claim that E protein promotes the formation of "cation-selective channels". However, whether this term represents specificity to certain ions (e.g., potassium or calcium) or the partial or total exclusion of anions is debatable. Herein, we discuss this claim based on the available data for SARS-CoV-1 and -2 E and on new experiments performed using the untagged full-length E protein from SARS-CoV-2 in planar lipid membranes of different types, including those that closely mimic the ERGIC membrane composition. We provide evidence that the selectivity of the E-induced channels is very mild and depends strongly on lipid environment. Thus, despite past and recent claims, we found no indication that the E protein forms cation-selective channels that prevent anion transport, and even less that E protein forms bona fide specific calcium channels. In fact, the E channel maintains its multi-ionic non-specific neutral character even in concentrated solutions of Ca2+ ions. Also, in contrast to previous studies, we found no evidence that SARS-CoV-2 E channel activation requires a particular voltage, high calcium concentrations or low pH, in agreement with available data from SARS-CoV-1 E. In addition, sedimentation velocity experiments suggest that the E channel population is mostly pentameric, but very dynamic and probably heterogeneous, consistent with the broad distribution of conductance values typically found in electrophysiological experiments. The latter has been explained by the presence of proteolipidic channel structures.

Frequency-dependent avoidance movement of glass catfish in response to sinusoidal electrical stimulation and associated spiking patterns of electroreceptors.

The glass catfish is a freshwater fish with electroreceptors on its body surface. In this study, we investigated its behavioral response to sinusoidal electrical stimulation with a dipole wider than its body length and the spiking patterns of its electroreceptors. We observed that sinusoidal electric stimulation with a large dipole distance elicited in the glass catfish an avoidance movement whose frequency range is frequency-dependent. The movements were prominent in the frequency range between 10-20 Hz. When the stimulation strength increased, the movements were also found in the low-frequency range. In electrophysiological experiments, periodic interspike intervals of the electroreceptors were modulated by sinusoidal electrical stimuli. The stimulation introduced irregularity in the spiking patterns. The local variability of the spike modulations was significantly higher in the frequency range of 4-40 Hz and was particularly sensitive at 20 Hz. The avoidance movements and an increase in the local variability in the spike patterns were found around 20 Hz. Our results indicate that the glass catfish avoids sinusoidal electrical stimulation in a frequency-dependent manner, and this is associated with local modulations in the spiking patterns of the electroreceptors.

Probing electrophysiological activity of amphiphilic Dynorphin A in planar neutral membranes reveals both ion channel-like activity and neuropeptide translocation

Dynorphin A (DynA) is an endogenous neuropeptide that besides acting as a ligand of the κ-opioid receptor, presents some non-opioid pathophysiological properties associated to its ability to induce cell permeability similarly to cell-penetrating peptides (CPPs). Here, we use electrophysiology experiments to show that amphiphilic DynA generates aqueous pores in neutral membranes similar to those reported previously in charged membranes, but we also find other events thermodynamically incompatible with voltage-driven ion channel activity (i.e. non-zero currents with no applied voltage in symmetric salt conditions, reversal potentials that exceed the theoretical limit for a given salt concentration gradient). By comparison with current traces generated by other amphiphilic molecule known to spontaneously cross membranes, we hypothesize that DynA could directly translocate across neutral bilayers, a feature never observed in charged membranes following the same electrophysiological protocol. Our findings suggest that DynA interaction with the cellular membrane is modulated by the lipid charge distribution, enabling either passive ionic transport via membrane remodeling and pore formation or by peptide direct internalization independent of cellular transduction pathways.

Variance analysis as a method to predict the locus of plasticity at populations of non-uniform synapses.

Our knowledge on synaptic transmission in the central nervous system has often been obtained by evoking synaptic responses to populations of synapses. Analysis of the variance in synaptic responses can be applied as a method to predict whether a change in synaptic responses is a consequence of altered presynaptic neurotransmitter release or postsynaptic receptors. However, variance analysis is based on binomial statistics, which assumes that synapses are uniform. In reality, synapses are far from uniform, which questions the reliability of variance analysis when applying this method to populations of synapses. To address this, we used an in silico model for evoked synaptic responses and compared variance analysis outcomes between populations of uniform versus non-uniform synapses. This simulation revealed that variance analysis produces similar results irrespectively of the grade of uniformity of synapses. We put this variance analysis to the test with an electrophysiology experiment using a model system for which the loci of plasticity are well established: the effect of amyloid-β on synapses. Variance analysis correctly predicted that postsynaptically produced amyloid-β triggered predominantly a loss of synapses and a minor reduction of postsynaptic currents in remaining synapses with little effect on presynaptic release probability. We propose that variance analysis can be reliably used to predict the locus of synaptic changes for populations of non-uniform synapses.

CXCR5 Regulates Neuronal Polarity Development and Migration in the Embryonic Stage via F-Actin Homeostasis and Results in Epilepsy-Related Behavior.

Epilepsy is a common, chronic neurological disorder that has been associated with impaired neurodevelopment and immunity. The chemokine receptor CXCR5 is involved in seizures via an unknown mechanism. Here, we first determined the expression pattern and distribution of the CXCR5 gene in the mouse brain during different stages of development and the brain tissue of patients with epilepsy. Subsequently, we found that the knockdown of CXCR5 increased the susceptibility of mice to pentylenetetrazol- and kainic acid-induced seizures, whereas CXCR5 overexpression had the opposite effect. CXCR5 knockdown in mouse embryos via viral vector electrotransfer negatively influenced the motility and multipolar-to-bipolar transition of migratory neurons. Using a human-derived induced an in vitro multipotential stem cell neurodevelopmental model, we determined that CXCR5 regulates neuronal migration and polarization by stabilizing the actin cytoskeleton during various stages of neurodevelopment. Electrophysiological experiments demonstrated that the knockdown of CXCR5 induced neuronal hyperexcitability, resulting in an increased number of seizures. Finally, our results suggested that CXCR5 deficiency triggers seizure-related electrical activity through a previously unknown mechanism, namely, the disruption of neuronal polarity.

Optimizing metabolic stability of phosphodiesterase 5 inhibitors: Discovery of a potent N-(pyridin-3-ylmethyl)quinoline derivative targeting synaptic plasticity

Phosphodiesterase 5 (PDE5) is a cyclic guanosine monophosphate-degrading enzyme involved in numerous biological pathways. Inhibitors of PDE5 are important therapeutics for the treatment of neurodegenerative diseases, including Alzheimer’s disease (AD). We previously reported the first generation of quinoline-based PDE5 inhibitors for the treatment of AD. However, the short in vitro microsomal stability rendered them unsuitable drug candidates. Here we report a series of new quinoline-based PDE5 inhibitors. Among them, compound 4b, 8-cyclopropyl-3-(hydroxymethyl)-4-(((6-methoxypyridin-3-yl)methyl)amino)quinoline-6-carbonitrile, shows a PDE5 IC50 of 20 nM and improved in vitro microsomal stability (t1/2 = 44.6 min) as well as excellent efficacy in restoring long-term potentiation, a type of synaptic plasticity to underlie memory formation, in electrophysiology experiments with a mouse model of AD. These results provide an insight into the development of a new class of PDE5 inhibitors for the treatment of AD.

Licochalcone Mediates the Pain Relief by Targeting the Voltage-Gated Sodium Channel.

Licorice is a traditional Chinese medicine and recorded to have pain relief effects in national pharmacopoeia, but the mechanisms behind these effects have not been fully explored. Among the hundreds of compounds in licorice, licochalcone A (LCA) and licochalcone B (LCB) are two important components belonging to the chalcone family. In this study, we compared the analgesic effects of these two licochalcones and the molecular mechanisms. LCA and LCB were applied in cultured dorsal root ganglion (DRG) neurons, and the voltage-gated sodium (NaV) currents and action potentials were recorded. The electrophysiological experiments showed that LCA can inhibit NaV currents and dampen excitabilities of DRG neurons, whereas LCB did not show inhibition effect on NaV currents. Because the NaV1.7 channel can modulate Subthreshold membrane potential oscillations in DRG neuron, which can palliate neuropathic pain, HEK293T cells were transfected with NaV1.7 channel and recorded with whole-cell patch clamp. LCA can also inhibit NaV1.7 channels exogenously expressed in HEK293T cells. We further explored the analgesic effects of LCA and LCB on formalin-induced pain animal models. The animal behavior tests revealed that LCA can inhibit the pain responses during phase 1 and phase 2 of formalin test, and LCB can inhibit the pain responses during phase 2. The differences of the effects on NaV currents between LCA and LCB provide us with the basis for developing NaV channel inhibitors, and the novel findings of analgesic effects indicate that licochalcones can be developed into effective analgesic medicines. SIGNIFICANCE STATEMENT: This study found that licochalcone A (LCA) can inhibit voltage-gated sodium (NaV) currents, dampen excitabilities of dorsal root ganglion neurons, and inhibit the NaV1.7 channels exogenously expressed in HEK293T cells. Animal behavior tests showed that LCA can inhibit the pain responses during phase 1 and phase 2 of formalin test, whereas licochalcone B can inhibit the pain responses during phase 2. These findings indicate that licochalcones could be the leading compounds for developing NaV channel inhibitors and effective analgesic medicines.

An E280K Missense Variant in KCND3/Kv4.3—Case Report and Functional Characterization

A five-year-old girl presented with headache attacks, clumsiness, and a history of transient gait disturbances. She and her father, mother, twin sister, and brother underwent neurological evaluation, neuroimaging, and exome sequencing covering 357 genes associated with movement disorders. Sequencing revealed the new variant KCND3 c.838G>A, p.E280K in the father and sisters, but not in the mother and brother. KCND3 encodes voltage-gated potassium channel D3 (Kv4.3) and mutations have been associated with spinocerebellar ataxia type 19/22 (SCA19/22) and cardiac arrhythmias. SCA19/22 is characterized by ataxia, Parkinsonism, peripheral neuropathy, and sometimes, intellectual disability. Neuroimaging, EEG, and ECG were unremarkable. Mild developmental delay with impaired fluid reasoning was observed in both sisters, but not in the brother. None of the family members demonstrated ataxia or parkinsonism. In Xenopus oocyte electrophysiology experiments, E280K was associated with a rightward shift in the Kv4.3 voltage-activation relationship of 11 mV for WT/E280K and +17 mV for E280K/E280K relative to WT/WT. Steady-state inactivation was similarly right-shifted. Maximal peak current amplitudes were similar for WT/WT, WT/E280K, and E280K/E280K. Our data indicate that Kv4.3 E280K affects channel activation and inactivation and is associated with developmental delay. However, E280K appears to be relatively benign considering it does not result in overt ataxia.

Design and implementation of high sampling rate and multichannel wireless recorder for EEG monitoring and SSVEP response detection.

The collection and process of human brain activity signals play an essential role in developing brain-computer interface (BCI) systems. A portable electroencephalogram (EEG) device has become an important tool for monitoring brain activity and diagnosing mental diseases. However, the miniaturization, portability, and scalability of EEG recorder are the current bottleneck in the research and application of BCI. For scalp EEG and other applications, the current study designs a 32-channel EEG recorder with a sampling rate up to 30 kHz and 16-bit accuracy, which can meet both the demands of scalp and intracranial EEG signal recording. A fully integrated electrophysiology microchip RHS2116 controlled by FPGA is employed to build the EEG recorder, and the design meets the requirements of high sampling rate, high transmission rate and channel extensive. The experimental results show that the developed EEG recorder provides a maximum 30 kHz sampling rate and 58 Mbps wireless transmission rate. The electrophysiological experiments were performed on scalp and intracranial EEG collection. An inflatable helmet with adjustable contact impedance was designed, and the pressurization can improve the SNR by approximately 4 times, the average accuracy of steady-state visual evoked potential (SSVEP) was 93.12%. Animal experiments were also performed on rats, and spike activity was captured successfully. The designed multichannel wireless EEG collection system is simple and comfort, the helmet-EEG recorder can capture the bioelectric signals without noticeable interference, and it has high measurement performance and great potential for practical application in BCI systems.

Behavioral and Electrophysiological Study on Eight Japanese Papilio Species with Five Hostplant Volatiles and Linalool

An electroantennogram (EAG) technique compared the antennal olfactory responses by both sexes of eight Japanese Papilio species with known host plants in laboratory experiments. Papilio species were collected from Honshû and Kyûshû (Japanese islands). The behavioral responses to volatile leaf substances from Citrus deliciosa, Zanthoxylum ailanthoides, Phellodendron amurense, Orixa japonica, and Foeniculum vulgare were examined in laboratory experiments. Individual EAG reactions were recorded. The results were very similar to the empirical field observations. The electrophysiological results of both sexes showed that the volatile substances released from non-preferred plants mainly elicited more significant EAG responses than the volatile substances from preferred host plants. Moreover, we performed behavioral experiments using eight female butterflies and their responses to five host plant species. An association between host plant selection behavior and taxonomical classification exists within the Papilio genus. The EAG responses were small when exposed to the plants with high scores in the behavioral experiments. Host plant preference patterns seem to be related to the volatile substances within the host plants. The butterflies responded to Linalool in both the behavioral and electrophysiological experiments.

Two Ascending Thermosensory Pathways from the Lateral Parabrachial Nucleus That Mediate Behavioral and Autonomous Thermoregulation.

Thermoregulatory behavior in homeothermic animals is an innate behavior to defend body core temperature from environmental thermal challenges in coordination with autonomous thermoregulatory responses. In contrast to the progress in understanding the central mechanisms of autonomous thermoregulation, those of behavioral thermoregulation remain poorly understood. We have previously shown that the lateral parabrachial nucleus (LPB) mediates cutaneous thermosensory afferent signaling for thermoregulation. To understand the thermosensory neural network for behavioral thermoregulation, in the present study, we investigated the roles of ascending thermosensory pathways from the LPB in avoidance behavior from innocuous heat and cold in male rats. Neuronal tracing revealed two segregated groups of LPB neurons projecting to the median preoptic nucleus (MnPO), a thermoregulatory center (LPB→MnPO neurons), and those projecting to the central amygdaloid nucleus (CeA), a limbic emotion center (LPB→CeA neurons). While LPB→MnPO neurons include separate subgroups activated by heat or cold exposure of rats, LPB→CeA neurons were only activated by cold exposure. By selectively inhibiting LPB→MnPO or LPB→CeA neurons using tetanus toxin light chain or chemogenetic or optogenetic techniques, we found that LPB→MnPO transmission mediates heat avoidance, whereas LPB→CeA transmission contributes to cold avoidance. In vivo electrophysiological experiments showed that skin cooling-evoked thermogenesis in brown adipose tissue requires not only LPB→MnPO neurons but also LPB→CeA neurons, providing a novel insight into the central mechanism of autonomous thermoregulation. Our findings reveal an important framework of central thermosensory afferent pathways to coordinate behavioral and autonomous thermoregulation and to generate the emotions of thermal comfort and discomfort that drive thermoregulatory behavior.SIGNIFICANCE STATEMENT Coordination of behavioral and autonomous thermoregulation is important for maintaining thermal homeostasis in homeothermic animals. However, the central mechanism of thermoregulatory behaviors remains poorly understood. We have previously shown that the lateral parabrachial nucleus (LPB) mediates ascending thermosensory signaling that drives thermoregulatory behavior. In this study, we found that one pathway from the LPB to the median preoptic nucleus mediates heat avoidance, whereas the other pathway from the LPB to the central amygdaloid nucleus is required for cold avoidance. Surprisingly, both pathways are required for skin cooling-evoked thermogenesis in brown adipose tissue, an autonomous thermoregulatory response. This study provides a central thermosensory network that coordinates behavioral and autonomous thermoregulation and generates thermal comfort and discomfort that drive thermoregulatory behavior.

Cannabidiol inhibits Nav channels through two distinct binding sites

Cannabidiol (CBD), a major non-psychoactive phytocannabinoid in cannabis, is an effective treatment for some forms of epilepsy and pain. At high concentrations, CBD interacts with a huge variety of proteins, but which targets are most relevant for clinical actions is still unclear. Here we show that CBD interacts with Nav1.7 channels at sub-micromolar concentrations in a state-dependent manner. Electrophysiological experiments show that CBD binds to the inactivated state of Nav1.7 channels with a dissociation constant of about 50 nM. The cryo-EM structure of CBD bound to Nav1.7 channels reveals two distinct binding sites. One is in the IV-I fenestration near the upper pore. The other binding site is directly next to the inactivated “wedged” position of the Ile/Phe/Met (IFM) motif on the short linker between repeats III and IV, which mediates fast inactivation. Consistent with producing a direct stabilization of the inactivated state, mutating residues in this binding site greatly reduced state-dependent binding of CBD. The identification of this binding site may enable design of compounds with improved properties compared to CBD itself.

Functions of the auditory system of biting female mosquitoes (Diptera, Culicidae)

Female mosquitoes possess a complex auditory system, the biological function of which has not yet been fully understood. Male and female mosquitoes are known to mutually adjust the frequencies of their wingbeats when approaching each other. To make such interaction possible, they need to hear each other and to be able to discriminate frequencies. Some recent data indicate that biting female mosquitoes can also use acoustic channel to detect their hosts. One can expect that the parameters of mosquito’s hearing re ect the acoustic properties of noises or other sounds emitted by the host animals. In this regard, it is worth asking whether mosquitoes are able to detect humans by their voices. We studied female mosquitoes of Aedes ( Ochlerotatus ) excrucians Walker. They are abundant in the biotopes where people are likely to be found, for example, along the river banks and in the village parks. In electrophysiological experiments, we measured the frequency-threshold characteristics of auditory receptors. The highest sensitivity of most receptors was found in the frequency range from 40 to 140 Hz, with minimum threshold values of 32-40 dB SPVL (Sound Particle Velocity Level). A comparison of the frequency-threshold characteristics of female mosquitoes with the averaged spectra of human speech indicates that, in most cases, mosquitoes can hear human voices and can use them as a cue for nding and attacking humans.

Increased propensity for infantile spasms and altered neocortical excitation-inhibition balance in a mouse model of down syndrome carrying human chromosome 21

Children with Down syndrome (DS, trisomy of chromosome 21) have an increased risk of infantile spasms (IS). As an epileptic encephalopathy, IS may further impair cognitive function and exacerbate neurodevelopmental delays already present in children with DS. To investigate the pathophysiology of IS in DS, we induced IS-like epileptic spasms in a genetic mouse model of DS that carries human chromosome 21q, TcMAC21, the animal model most closely representing gene dosage imbalance in DS. Repetitive extensor/flexor spasms were induced by the GABAB receptor agonist γ-butyrolactone (GBL) and occurred predominantly in young TcMAC21 mice (85%) but also in some euploid mice (25%). During GBL application, background electroencephalographic (EEG) amplitude was reduced, and rhythmic, sharp-and-slow wave activity or high-amplitude burst (epileptiform) events emerged in both TcMAC21 and euploid mice. Spasms occurred only during EEG bursts, but not every burst was accompanied by a spasm. Electrophysiological experiments revealed that basic membrane properties (resting membrane potential, input resistance, action-potential threshold and amplitude, rheobase, input-output relationship) of layer V pyramidal neurons were not different between TcMAC21 mice and euploid controls. However, excitatory postsynaptic currents (EPSCs) evoked at various intensities were significantly larger in TcMAC21 mice than euploid controls, while inhibitory postsynaptic currents (IPSCs) were similar between the two groups, resulting in an increased excitation-inhibition (E-I) ratio. These data show that behavioral spasms with epileptic EEG activity can be induced in young TcMAC21 DS mice, providing proof-of-concept evidence for increased IS susceptibility in these DS mice. Our findings also show that basic membrane properties are similar in TcMAC21 and euploid mice, while the neocortical E-I balance is altered to favor increased excitation in TcMAC21 mice, which may predispose to IS generation.

Adaptive closed-loop paradigm of electrophysiology for neuron models

The traditional electrophysiological experiments based on an open-loop paradigm are relatively complicated and limited when facing an individual neuron with uncertain nonlinear factors. Emerging neural technologies enable tremendous growth in experimental data leading to the curse of high-dimensional data, which obstructs the mechanism exploration of spiking activities in the neurons. In this work, we propose an adaptive closed-loop electrophysiology simulation experimental paradigm based on a Radial Basis Function neural network and a highly nonlinear unscented Kalman filter. On account of the complex nonlinear dynamic characteristics of the real neurons, the proposed simulation experimental paradigm could fit the unknown neuron models with different channel parameters and different structures (i.e. single or multiple compartments), and further compute the injected stimulus in time according to the arbitrary desired spiking activities of the neurons. However, the hidden electrophysiological states of the neurons are difficult to be measured directly. Thus, an extra Unscented Kalman filter modular is incorporated in the closed-loop electrophysiology experimental paradigm. The numerical results and theoretical analyses demonstrate that the proposed adaptive closed-loop electrophysiology simulation experimental paradigm achieves desired spiking activities arbitrarily and the hidden dynamics of the neurons are visualized by the unscented Kalman filter modular. The proposed adaptive closed-loop simulation experimental paradigm can avoid the inefficiency of data at increasingly greater scales and enhance the scalability of electrophysiological experiments, thus speeding up the discovery cycle on neuroscience.