The TD Drive: A Parametric, Open-Source Implant for Multi-Area Electrophysiological Recordings in Behaving and Sleeping Rats.

Intricate interactions between multiple brain areas underlie most functions attributed to the brain. The process of learning, as well as the formation and consolidation of memories, are two examples that rely heavily on functional connectivity across the brain. In addition, investigating hemispheric similarities and/or differences goes hand in hand with these multi-area interactions. Electrophysiological studies trying to further elucidate these complex processes thus depend on recording brain activity at multiple locations simultaneously and often in a bilateral fashion. Presented here is a 3D-printable implant for rats, named TD Drive, capable of symmetric, bilateral wire electrode recordings, currently in up to ten distributed brain areas simultaneously. The open-source design was created employing parametric design principles, allowing prospective users to easily adapt the drive design to their needs by simply adjusting high-level parameters, such as anterior-posterior and mediolateral coordinates of the recording electrode locations. The implant design was validated in n = 20 Lister Hooded rats that performed different tasks. The implant was compatible with tethered sleep recordings and open field recordings (Object Exploration) as well as wireless recording in a large maze using two different commercial recording systems and headstages. Thus, presented here is the adaptable design and assembly of a new electrophysiological implant, facilitating fast preparation and implantation.

Research progress on insect visual electrophysiological techniques.

Insect visual electrophysiological techniques are important to study the electrical characteristics of photoreceptor cells and visual neurons in insects, including electroretinography (ERG) and microelectrode intracellular recording (MIR). ERG records the changes of voltage or electric current in the retina of insects in response to different light stimuli, which occurs outside the cell. MIR records the changes in individual photoreceptor cells or visual neurons of an insect exposed to different lights, which occurs inside the cell. Insect visual electrophysiological techniques can explore the mechanism of electrophysiological response of insects' vision to light and reveal their sensitive light spectra and photoreceptor types. This review introduced the basic structure and the principle of ERG and MIR, and summarized their applications in insect researches in the past 20 years, which would provide references for elucidating the mechanism of light perception in insects and the use of insect phototropism to control pests.

Recording Cilia Activity in Ctenophores.

Pelagic ctenophores swim in the water with the help of eight rows of long fused cilia. Their entire behavioral repertoire is dependent to a large degree on coordinated cilia activity. Therefore, recording cilia beating is paramount to understanding and registering the behavioral responses and investigating its neural and hormonal control. Here, we present a simple protocol to monitor and quantify cilia activity in semi-intact ctenophore preparations (using Pleurobrachia and Bolinopsis as models), which includes a standard electrophysiological setup for intracellular recording.

Electrophysiology of Ctenophore Smooth Muscle.

Unlike in the Cnidaria, where muscle cells are coupled together into an epithelium, ctenophore muscles are single, elongated, intramesogleal structures resembling vertebrate smooth muscle. Under voltage-clamp, these fibers can be separated into different classes with different sets of membrane ion channels. The ion channel makeup is related to the muscle's anatomical position and specific function. For example, Beroe ovata radial fibers, which are responsible for maintaining the rigidity of the body wall, generate sequences of brief action potentials whereas longitudinal fibers, which are concerned with mouth opening and body flexions, often produce single longer duration action potentials.Beroe muscle contractions depend on the influx of Ca2+. During an action potential the inward current is carried by Ca2+, and the increase in intracellular Ca2+ concentration generated can be monitored in FLUO-3-loaded cells. Confocal microscopy in line scan mode shows that the Ca2+ spreads from the outer membrane into the core of the fiber and is cleared from there relatively slowly. The rise in intracellular Ca2+ is linked to an increase in a Ca2+-activated K+ conductance (KCa), which can also be elicited by iontophoretic Ca2+ injection. Near the cell membrane, Ca2+ clearance monitored using FLUO3, matches the decline in the KCa conductance. For light loads, Ca2+ is cleared rapidly, but this fast system is insufficient when Ca2+ influx is maintained. Action potential frequency may be regulated by the slowly developing KCa conductance.

Statistical segmentation model for accurate electrode positioning in Parkinson's deep brain stimulation based on clinical low-resolution image data and electrophysiology.

BACKGROUND: Deep Brain Stimulation (DBS), applying chronic electrical stimulation of subcortical structures, is a clinical intervention applied in major neurologic disorders. In order to achieve a good clinical effect, accurate electrode placement is necessary. The primary localisation is typically based on presurgical MRI imaging, often followed by intra-operative electrophysiology recording to increase the accuracy and to compensate for brain shift, especially in cases where the surgical target is small, and there is low contrast: e.g., in Parkinson's disease (PD) and in its common target, the subthalamic nucleus (STN). METHODS: We propose a novel, fully automatic method for intra-operative surgical navigation. First, the surgical target is segmented in presurgical MRI images using a statistical shape-intensity model. Next, automated alignment with intra-operatively recorded microelectrode recordings is performed using a probabilistic model of STN electrophysiology. We apply the method to a dataset of 120 PD patients with clinical T2 1.5T images, of which 48 also had available microelectrode recordings (MER). RESULTS: The proposed segmentation method achieved STN segmentation accuracy around dice = 0.60 compared to manual segmentation. This is comparable to the state-of-the-art on low-resolution clinical MRI data. When combined with electrophysiology-based alignment, we achieved an accuracy of 0.85 for correctly including recording sites of STN-labelled MERs in the final STN volume. CONCLUSION: The proposed method combines image-based segmentation of the subthalamic nucleus with microelectrode recordings to estimate their mutual location during the surgery in a fully automated process. Apart from its potential use in clinical targeting, the method can be used to map electrophysiological properties to specific parts of the basal ganglia structures and their vicinity.

Integration of in vivo electrophysiology and optogenetics in rodents with PEDOT:PSS neural electrode array.

Here, we present a protocol for the fabrication of transparent implantable electrode arrays for integrating optogenetics and electrophysiology. We describe steps for fabricating microelectrodes using the conductive polymer poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate). We then detail procedures for analyzing performance of the electrodes and recording light-evoked neural activities from the transgenic mouse. This protocol utilizes photolithography rather than conventional electrodeposition. For complete details on the use and execution of this protocol, please refer to Cho et al. (2022).1.

Single shot detection of alterations across multiple ionic currents from assimilation of cell membrane dynamics.

The dysfunction of ion channels is a causative factor in a variety of neurological diseases, thereby defining the implicated channels as key drug targets. The detection of functional changes in multiple specific ionic currents currently presents a challenge, particularly when the neurological causes are either a priori unknown, or are unexpected. Traditional patch clamp electrophysiology is a powerful tool in this regard but is low throughput. Here, we introduce a single-shot method for detecting alterations amongst a range of ion channel types from subtle changes in membrane voltage in response to a short chaotically driven current clamp protocol. We used data assimilation to estimate the parameters of individual ion channels and from these we reconstructed ionic currents which exhibit significantly lower error than the parameter estimates. Such reconstructed currents thereby become sensitive predictors of functional alterations in biological ion channels. The technique correctly predicted which ionic current was altered, and by approximately how much, following pharmacological blockade of BK, SK, A-type K+ and HCN channels in hippocampal CA1 neurons. We anticipate this assay technique could aid in the detection of functional changes in specific ionic currents during drug screening, as well as in research targeting ion channel dysfunction.

Improved seizure liability detection by combining rat hippocampal brain slice electrophysiology with in vivo behavior observation following intracerebroventricular drug administration.

An adverse effect of drug candidates, seizure is a serious issue in drug development. Improving evaluation systems for seizure liability is crucial for selecting good candidates. Firstly, in vitro electrophysiological measurement by a multielectrode array system in rat hippocampal brain slices was employed to confirm an increase in electrically evoked population spike (PS) area, the occurrence of multiple population spikes (MPSs), and thereby the seizure liability of five positive control chemicals: picrotoxin, 4-aminopyridine, pentylenetetrazole, penicillin G, and chlorpromazine. Aspirin, a negative control, did not affect PS area or generate MPSs. Furthermore, baclofen, an anticonvulsant drug, decreased PS area and inhibited the increase in PS area or occurrence of MPSs induced by picrotoxin. A comparative study of seizure liability among carbapenem antibiotics revealed that tienam > carbenin > omegacin and finibax. Despite leading to a strong decrease in PS area, physostigmine, cisplatin, and paroxetine still produced MPSs. Therefore, the increase in PS area or the occurrence of the MPS are considered significant evaluation parameters for seizure liability. In contrast, the in vitro electrophysiological measurement could not detect the seizure liability of diphenhydramine or fluvoxamine. A follow-up study of in vivo mouse behavioral change induced by intracerebroventricular administration of these drugs clearly detected convulsions. The in vitro electrophysiological study using hippocampal brain slices combined with in vivo behavior observation study of drug candidates administered by intracerebroventricular injection can implement to assess the seizure liability of even small amounts, especially in the early stages of drug development.

Flexible and stretchable implantable devices for peripheral neuromuscular electrophysiology.

The peripheral nervous and muscular system, a cornerstone of human physiology, plays a pivotal role in ensuring the seamless functioning of the human body. This intricate network, comprising nerves and muscles extending throughout the body, is essential for motor control, sensory feedback, and the regulation of autonomic bodily functions. The qualified implantable peripheral interface can accurately monitor the biopotential of the target tissue and conduct treatment with stimulation, enhancing the human-machine interaction and new achievements in disease cure. Implantable electrodes have revolutionized the field of neuromuscular interfaces, offering precise bidirectional communication between the neuromuscular system and external devices. They enable natural control for individuals with limb loss, bridging the gap between mind and machine and aiding neuromuscular rehabilitation. In research and medical diagnostics, implantable electrodes provide invaluable tools for studying neuromuscular function and the development of therapies. However, traditional rigid electrodes face challenges due to the dynamic nature of the peripheral neuromuscular system. Flexible and stretchable devices show immense promise in accommodating dynamic alterations, offering adaptability, and accurate monitoring of electrophysiological signals. This review delves into the challenges associated with the peripheral interface, primarily focusing on monitoring and stimulation. It then provides a summary of common materials and structural design optimizations, discusses technologies for enhancing interface adhesion and surface functionalization, and explores encapsulation methods for implanted devices. Recent advancements in energy supply and the applications of implantable, flexible, and stretchable devices are also comprehensively reviewed, with due consideration given to ethical concerns and signal analysis. The promising directions are finally presented to provide enlightenment for high-performance sensor-tissue interfaces in the future, which will promote profound progress in clinical and human-machine interaction research. Flexible and stretchable devices are at the forefront of healthcare, with the potential to transform the treatment of neuromuscular disorders and enhance human augmentation, blurring the lines between natural and artificial limbs. They represent a promising avenue for the future, with exciting applications in healthcare, science, and technology, promising to bring us closer to the seamless integration of human and machine in the realm of neuromuscular interfaces.

Beyond a Transmission Cable-New Technologies to Reveal the Richness in Axonal Electrophysiology.

The axon is a neuronal structure capable of processing, encoding, and transmitting information. This assessment contrasts with a limiting, but deeply rooted, perspective where the axon functions solely as a transmission cable of somatodendritic activity, sending signals in the form of stereotypical action potentials. This perspective arose, at least partially, because of the technical difficulties in probing axons: their extreme length-to-diameter ratio and intricate growth paths preclude the study of their dynamics through traditional techniques. Recent findings are challenging this view and revealing a much larger repertoire of axonal computations. Axons display complex signaling processes and structure-function relationships, which can be modulated via diverse activity-dependent mechanisms. Additionally, axons can exhibit patterns of activity that are dramatically different from those of their corresponding soma. Not surprisingly, many of these recent discoveries have been driven by novel technology developments, which allow for in vitro axon electrophysiology with unprecedented spatiotemporal resolution and signal-to-noise ratio. In this review, we outline the state-of-the-art in vitro toolset for axonal electrophysiology and summarize the recent discoveries in axon function it has enabled. We also review the increasing repertoire of microtechnologies for controlling axon guidance which, in combination with the available cutting-edge electrophysiology and imaging approaches, have the potential for more controlled and high-throughput in vitro studies. We anticipate that a larger adoption of these new technologies by the neuroscience community will drive a new era of experimental opportunities in the study of axon physiology and consequently, neuronal function.

Synchronous monitoring of brain-heart electrophysiology using heart rate variability coupled with rapid quantitative electroencephalography in orthostatic hypotension patients with α-synucleinopathies: Rapid prediction of orthostatic hypotension and preliminary exploration of brain stimulation therapy.

BACKGROUND: In α-synucleinopathies, the dysfunction of the autonomic nervous system which typically manifests as orthostatic hypotension (OH) often leads to severe consequences and poses therapeutic challenges. This study aims to discover the brain-cardiac electrophysiological changes in OH patients with α-synucleinopathies using the rapid quantitative electroencephalography (qEEG) coupled with heart rate variability (HRV) technique to identify rapid, noninvasive biomarkers for early warning and diagnosis, as well as shed new light on complementary treatment approaches such as brain stimulation targets. METHODS: In this study, 26 subjects of α-synucleinopathies with OH (α-OH group), 21 subjects of α-synucleinopathies without OH (α-NOH group), and 34 healthy controls (control group) were included from September 2021 to August 2023 (NCT05527067). The heart rate-blood pressure variations in supine and standing positions were monitored, and synchronization parameters of seated resting-state HRV coupled with qEEG were collected. Time-domain and frequency-domain of HRV measures as well as peak frequency and power of the brainwaves were extracted. Differences between these three groups were compared, and correlations between brain-heart parameters were analyzed. RESULTS: The research results showed that the time-domain parameters such as MxDMn, pNN50, RMSSD, and SDSD of seated resting-state HRV exhibited a significant decrease only in the α-OH group compared to the healthy control group (p < 0.05), while there was no significant difference between the α-NOH group and the healthy control group. Several time-domain and frequency-domain parameters of seated resting-state HRV were found to be correlated with the blood pressure changes within the first 5 min of transitioning from supine to standing position (p < 0.05). Differences were observed in the power of beta1 waves (F4 and Fp2) and beta2 waves (Fp2 and F4) in the seated resting-state qEEG between the α-OH and α-NOH groups (p < 0.05). The peak frequency of theta waves in the Cz region also showed a difference (p < 0.05). The power of beta2 waves in the Fp2 and F4 brain regions correlated with frequency-domain parameters of HRV (p < 0.05). Additionally, abnormal electrical activity in the alpha, theta, and beta1 waves was associated with changes in heart rate and blood pressure within the first 5 min of transitioning from supine to standing position (p < 0.05). CONCLUSION: Rapid resting-state HRV with certain time-domain parameters below normal levels may serve as a predictive indicator for the occurrence of orthostatic hypotension (OH) in patients with α-synucleinopathies. Additionally, the deterioration of HRV parameters correlates with synchronous abnormal qEEG patterns, which can provide insights into the brain stimulation target areas for OH in α-synucleinopathy patients.

Membrane-coated glass electrodes for stable, low-noise electrophysiology recordings in Drosophila central neurons.

BACKGROUND: Electrophysiological recording with glass electrodes is one of the best techniques to measure membrane potential dynamics and ionic currents of voltage-gated channels in neurons. However, artifactual variability of the biophysical state variables that determine recording quality can be caused by insufficient affinity between the electrode and cell membrane during the recording. NEW METHOD: We introduce a phospholipid membrane coating on glass electrodes to improve intracellular electrophysiology recording quality. Membrane-coated electrodes were prepared with a tip-dip protocol for perforated-patch, sharp-electrode current-clamp, and cell-attached patch-clamp recordings from specific circadian clock neurons in Drosophila. We perform quantitative comparisons based on the variability of functional biophysical parameters used in various electrophysiological methods, and advanced statistical comparisons based on the degree of stationariness and signal-to-noise ratio. RESULTS: Results indicate a dramatic reduction in artifactual variabilities of functional parameters from enhanced stability. We also identify significant exclusions of a statistically estimated noise component in a time series of membrane voltage signals, improving signal-to-noise ratio. COMPARISON WITH EXISTING METHODS: Compared to standard glass electrodes, using membrane-coated glass electrodes achieves improved recording quality in intracellular electrophysiology. CONCLUSIONS: Electrophysiological recordings from Drosophila central neurons can be technically challenging, however, membrane-coated electrodes will possibly be beneficial for reliable data acquisition and improving the technical feasibility of axonal intracellular activities measurements and single-channel recordings. The improved electrical stability of the recordings should also contribute to increased mechanical stability, thus facilitating long-term stable measurements of neural activity. Therefore, it is possible that membrane-coated electrodes will be useful for any model system.

Pharmacological Management of Cardiac Arrhythmias in the Fetal and Neonatal Periods: A Scientific Statement From the American Heart Association: Endorsed by the Pediatric & Congenital Electrophysiology Society (PACES).

Disorders of the cardiac rhythm may occur in both the fetus and neonate. Because of the immature myocardium, the hemodynamic consequences of either bradyarrhythmias or tachyarrhythmias may be far more significant than in mature physiological states. Treatment options are limited in the fetus and neonate because of limited vascular access, patient size, and the significant risk/benefit ratio of any intervention. In addition, exposure of the fetus or neonate to either persistent arrhythmias or antiarrhythmic medications may have yet-to-be-determined long-term developmental consequences. This scientific statement discusses the mechanism of arrhythmias, pharmacological treatment options, and distinct aspects of pharmacokinetics for the fetus and neonate. From the available current data, subjects of apparent consistency/consensus are presented, as well as future directions for research in terms of aspects of care for which evidence has not been established.

Multivariate classification of multichannel long-term electrophysiology data identifies different sleep stages in fruit flies.

Identifying different sleep stages in humans and other mammals has traditionally relied on electroencephalograms. Such an approach is not feasible in certain animals such as invertebrates, although these animals could also be sleeping in stages. Here, we perform long-term multichannel local field potential recordings in the brains of behaving flies undergoing spontaneous sleep bouts. We acquired consistent spatial recordings of local field potentials across multiple flies, allowing us to compare brain activity across awake and sleep periods. Using machine learning, we uncover distinct temporal stages of sleep and explore the associated spatial and spectral features across the fly brain. Further, we analyze the electrophysiological correlates of microbehaviors associated with certain sleep stages. We confirm the existence of a distinct sleep stage associated with rhythmic proboscis extensions and show that spectral features of this sleep-related behavior differ significantly from those associated with the same behavior during wakefulness, indicating a dissociation between behavior and the brain states wherein these behaviors reside.

A distinct cortical code for socially learned threat.

Animals can learn about sources of danger while minimizing their own risk by observing how others respond to threats. However, the distinct neural mechanisms by which threats are learned through social observation (known as observational fear learning1-4 (OFL)) to generate behavioural responses specific to such threats remain poorly understood. The dorsomedial prefrontal cortex (dmPFC) performs several key functions that may underlie OFL, including processing of social information and disambiguation of threat cues5-11. Here we show that dmPFC is recruited and required for OFL in mice. Using cellular-resolution microendoscopic calcium imaging, we demonstrate that dmPFC neurons code for observational fear and do so in a manner that is distinct from direct experience. We find that dmPFC neuronal activity predicts upcoming switches between freezing and moving state elicited by threat. By combining neuronal circuit mapping, calcium imaging, electrophysiological recordings and optogenetics, we show that dmPFC projections to the midbrain periaqueductal grey (PAG) constrain observer freezing, and that amygdalar and hippocampal inputs to dmPFC opposingly modulate observer freezing. Together our findings reveal that dmPFC neurons compute a distinct code for observational fear and coordinate long-range neural circuits to select behavioural responses.

Intrinsic running capacity associates with hippocampal electrophysiology and long-term potentiation in rats.

Good aerobic and metabolic fitness associates with better cognitive performance and brain health. Conversely, poor metabolic health predisposes to neurodegenerative diseases. Our previous findings indicate that rats selectively bred for Low Capacity for Running (LCR) show less synaptic plasticity and more inflammation in the hippocampus and perform worse in tasks requiring flexible cognition than rats bred for High Capacity for Running (HCR). Here we aimed to determine whether hippocampal electrophysiological activity related to learning and memory would be impaired in LCR compared to HCR rats. We also studied whether an exercise intervention could even out the possible differences. We conducted in vivo recordings from the dorsal hippocampus under terminal urethane anesthesia in middle-aged sedentary males and female rats, and in females allowed to access running wheels for 6 weeks. Our results indicate stronger long-term potentiation (LTP) in the CA3-CA1 synapse in HCR than LCR rats, and in female than male rats. Compared to LCR rats, HCR rats had more dentate spikes and more gamma epochs, the occurrence of which also correlated positively with the magnitude of LTP. Voluntary running reduced the differences between female LCR and HCR rats. In conclusion, low innate fitness links to reduced hippocampal function and plasticity which can seems to improve with voluntary aerobic exercise even in middle age.

Effect of ubiquinol on electrophysiology during high-altitude acclimatization and de-acclimatization: A substudy of the Shigatse CARdiorespiratory fitness (SCARF) randomized clinical trial.

BACKGROUND: High-altitude exposure changes the electrical conduction of the heart. However, reports on electrocardiogram (ECG) characteristics and potent prophylactic agents during high-altitude acclimatization and de-acclimatization are inadequate. This study aimed to investigate the effects of ubiquinol on electrophysiology after high-altitude hypoxia and reoxygenation. METHODS: The study was a prospective, randomized, double-blind, placebo-controlled trial. Forty-one participants were randomly divided into two groups receiving ubiquinol 200 mg daily or placebo orally 14 days before flying to high altitude (3900 m) until the end of the study. Cardiopulmonary exercise testing was performed at baseline (300 m), on the third day after reaching high altitude, and on the seventh day after returning to baseline. RESULTS: Acute high-altitude exposure prolonged resting ventricular repolarization, represented by increased corrected QT interval (455.9 ± 23.4 vs. 427.1 ± 19.1 ms, P < 0.001) and corrected Tpeak-Tend interval (155.5 ± 27.4 vs. 125.3 ± 21.1 ms, P < 0.001), which recovered after returning to low altitude. Ubiquinol supplementation shortened the hypoxia-induced extended Tpeak-Tend interval (-7.7 ms, [95% confidence interval (CI), -13.8 to -1.6], P = 0.014), Tpeak-Tend /QT interval (-0.014 [95% CI, -0.027 to -0.002], P = 0.028), and reserved maximal heart rate (11.9 bpm [95% CI, 3.2 to 20.6], P = 0.013) during exercise at high altitude. Furthermore, the decreased resting amplitude of the ST-segment in the V3 lead was correlated with decreased peak oxygen pulse (R = 0.713, P < 0.001) and maximum oxygen consumption (R = 0.595, P < 0.001). CONCLUSIONS: Our results illustrated the electrophysiology changes during high-altitude acclimatization and de-acclimatization. Similarly, ubiquinol supplementation shortened the prolonged Tpeak-Tend interval and reserved maximal heart rate during exercise at high altitude. REGISTRATION: URL: www.chictr.org.cn; Unique identifier: ChiCTR2200059900.

Analysis of the relationship between emotion intensity and electrophysiology parameters during a voice examination of opera singers.

OBJECTIVES: Emotions and stress affect voice production. There are only a few reports in the literature on how changes in the autonomic nervous system affect voice production. The aim of this study was to examine emotions and measure stress reactions during a voice examination procedure, particularly changes in the muscles surrounding the larynx. MATERIAL AND METHODS: The study material included 50 healthy volunteers (26 voice workers - opera singers, 24 control subjects), all without vocal complaints. All subjects had good voice quality in a perceptual assessment. The research procedure consisted of 4 parts: an ear, nose, and throat (ENT)­phoniatric examination, surface electromyography, recording physiological indicators (heart rate and skin resistance) using a wearable wristband, and a psychological profile based on questionnaires. RESULTS: The results of the study demonstrated that there was a relationship between positive and negative emotions and stress reactions related to the voice examination procedure, as well as to the tone of the vocal tract muscles. There were significant correlations between measures describing the intensity of experienced emotions and vocal tract muscle maximum amplitude of the cricothyroid (CT) and sternocleidomastoid (SCM) muscles during phonation and non-phonation tasks. Subjects experiencing eustress (favorable stress response) had increased amplitude of submandibular and CT at rest and phonation. Subjects with high levels of negative emotions, revealed positive correlations with SCMmax during the glissando. The perception of positive and negative emotions caused different responses not only in the vocal tract but also in the vegetative system. Correlations were found between emotions and physiological parameters, most markedly in heart rate variability. A higher incidence of extreme emotions was observed in the professional group. CONCLUSIONS: The activity of the vocal tract muscles depends on the type and intensity of the emotions and stress reactions. The perception of positive and negative emotions causes different responses in the vegetative system and the vocal tract. Int J Occup Med Environ Health. 2024;37(1):84-97.