Electrical Recordings Research Articles

Age-Related Changes in Neurons and Satellite Glial Cells in Mouse Dorsal Root Ganglia.

The effects of aging on the nervous system are well documented. However, most previous studies on this topic were performed on the central nervous system. The present study was carried out on the dorsal root ganglia (DRGs) of mice, and focused on age-related changes in DRG neurons and satellite glial cells (SGCs). Intracellular electrodes were used for dye injection to examine the gap junction-mediated coupling between neurons and SGCs, and for intracellular electrical recordings from the neurons. Tactile sensitivity was assessed with von Frey hairs. We found that 3-23% of DRG neurons were dye-coupled to SGCs surrounding neighboring neurons in 8-24-month (Mo)-old mice, whereas in young adult (3 Mo) mice, the figure was 0%. The threshold current for firing an action potential in sensory neurons was significantly lower in DRGs from 12 Mo mice compared with those from 3 Mo mice. The percentage of neurons with spontaneous subthreshold membrane potential oscillation was greater by two-fold in 12 Mo mice. The withdrawal threshold was lower by 22% in 12 Mo mice compared with 3 Mo ones. These results show that in the aged mice, a proportion of DRG neurons is coupled to SGCs, and that the membrane excitability of the DRG neurons increases with age. We propose that augmented neuron-SGC communications via gap junctions are caused by low-grade inflammation associated with aging, and this may contribute to pain behavior.

Open Citizen Science: fostering open knowledge with participation

Citizen Science or community science has been around for a long time. The scope of community involvement in Citizen Science initiatives ranges from short-term data collection to intensive engagement to delve into a research topic together with scientists and/or other volunteers. Although many volunteer researchers have academic training, it is not a prerequisite for participation in research projects. It is important to adhere to scientific standards, which include, above all, transparency with regard to the methodology of data collection and public discussion of the results, and open educational resources (OER). Hereby, Citizen Science is closely linked to Open Science. In our contribution, we will introduce two projects, both developed within the Wikimedia Fellowship Freies Wissen. The top-down approach: ERGo! An Entomology Research Tool to raise awareness of biodiversity protection. Inclusion in academia and pressing social problems such as climate change are fundamentally social justice issues. To facilitate early participation in the scientific process on the part of people holding underrepresented identities in science, we develop a Citizen Science initiative based on a low-cost open-source platform (ERGo!) to perform a technique for electrical recordings from insect eyes known as electroretinograms (ERGs) while presenting visual stimuli. Pasadena Unified School District High School students pilot ERG experiments to test the feasibility of this technique as a large-scale Citizen Science initiative. With ERGo!, future Citizen Scientists contribute data to cutting-edge research that monitors insect biodiversity, adaptation, and health in rapidly changing environments caused by monocultures, pesticides, and climate change. The bottom-up approach: Open cultural data collection. A Citizen Science initiative for regional knowledge curation. We catalogued the 18th century German magazine ‘Die Gartenlaube’ (in Wikisource) with bibliographic metadata in Wikidata in a project called ‘Die Datenlaube’. We develop collaborative approaches for linked open data methods to produce data sets about historical knowledge. The concept of ‘Open Citizen Science’ offers a methodological baseline for Open Science practises in fields of digital humanities. Scanned documents and structured open metadata revealed open access to historic collections. Through the Wikimedia platforms 'Die Datenlaube' creates possibilities to edit entries, to design own investigations, and to contribute to OER. Based on the elaboration of the two rather different projects (natural and social sciences, involvement of pupils vs citizens, top-down vs bottom-up), we will discuss similarities and hence the challenges and lessons learned for using and developing Open Science elements in Citizen Science and mutual learning. Furthermore, we will conclude by focusing on the opportunities resulting from the integration of societal expectations in science and vice versa.

Comparison of Dry and Wet Electrodes for Detecting Gastrointestinal Activity Patterns from Body Surface Electrical Recordings.

Gastrointestinal motility patterns can be mapped via electrical signals measured non-invasively on the body surface. However, short-term (≈2-4h) meal response studies as well as long-term monitoring (≥24h) may be hindered by skin irritation inherent with traditional Ag/AgCl pre-gelled ("wet") electrodes. The aim of this work was to investigate the practical utility of using dry electrodes for GI body-surface electrical measurements. To directly compare dry vs. wet electrodes, we simultaneously recorded electrical signals from both types arranged in a 9-electrode array during an ≈2.5h colonic meal-response study. Wavelet-based analyses were used to identify the signature post-meal colonic cyclic motor patterns. Blinded comparison of signal quality was carried out by four expert manual reviewers in order to assess the practical utility of each electrode type for identifying GI activity patterns. Dry electrodes recorded high-quality GI signals with signal-to-noise ratio of 10.0±3.5dB, comparable to that of wet electrodes (9.9±3.6dB). Although users rated dry electrodes as slightly more difficult to self-apply, they caused no skin irritation and were thus better tolerated overall. Dry electrodes are a more comfortable alternative to conventional wet electrode systems, and may offer a potentially viable option for long-term GI monitoring studies.

Arginine–vasopressin-expressing neurons in the murine suprachiasmatic nucleus exhibit a circadian rhythm in network coherence in vivo

The suprachiasmatic nucleus (SCN) is composed of functionally distinct subpopulations of GABAergic neurons which form a neural network responsible for synchronizing most physiological and behavioral circadian rhythms in mammals. To date, little is known regarding which aspects of SCN rhythmicity are generated by individual SCN neurons, and which aspects result from neuronal interaction within a network. Here, we utilize invivo miniaturized microscopy to measure fluorescent GCaMP-reported calcium dynamics in arginine vasopressin (AVP)-expressing neurons in the intact SCN of awake, behaving mice. We report that SCN AVP neurons exhibit periodic, slow calcium waves which we demonstrate, using invivo electrical recordings, likely reflect burst firing. Further, we observe substantial heterogeneity of function in that AVP neurons exhibit unstable rhythms, and relatively weak rhythmicity at the population level. Network analysis reveals that correlated cellular behavior, or coherence, among neuron pairs also exhibited stochastic rhythms with about 33% of pairs rhythmic at any time. Unlike single-cell variables, coherence exhibited a strong rhythm at the population level with time of maximal coherence among AVP neuronal pairs at CT/ZT 6 and 9, coinciding with the timing of maximal neuronal activity for the SCN as a whole. These results demonstrate robust circadian variation in the coordination between stochastically rhythmic neurons and that interactions between AVP neurons in the SCN may be more influential than single-cell activity in the regulation of circadian rhythms. Furthermore, they demonstrate that cells in this circuit, like those in many other circuits, exhibit profound heterogenicity of function over time and space.

Towards a mesoscale physical modeling framework for stereotactic-EEG recordings

Objective. Stereotactic-electroencephalography (SEEG) and scalp EEG recordings can be modeled using mesoscale neural mass population models (NMMs). However, the relationship between those mathematical models and the physics of the measurements is unclear. In addition, it is challenging to represent SEEG data by combining NMMs and volume conductor models due to the intermediate spatial scale represented by these measurements. Approach. We provide a framework combining the multi-compartmental modeling formalism and a detailed geometrical model to simulate the transmembrane currents that appear in layer 3, 5 and 6 pyramidal cells due to a synaptic input. With this approach, it is possible to realistically simulate the current source density (CSD) depth profile inside a cortical patch due to inputs localized into a single cortical layer and the induced voltage measured by two SEEG contacts using a volume conductor model. Based on this approach, we built a framework to connect the activity of a NMM with a volume conductor model and we simulated an example of SEEG signal as a proof of concept. Main results. CSD depends strongly on the distribution of the synaptic inputs onto the different cortical layers and the equivalent current dipole strengths display substantial differences (of up to a factor of four in magnitude in our example). Thus, the inputs coming from different neural populations do not contribute equally to the electrophysiological recordings. A direct consequence of this is that the raw output of NMMs is not a good proxy for electrical recordings. We also show that the simplest CSD model that can accurately reproduce SEEG measurements can be constructed from discrete monopolar sources (one per cortical layer). Significance. Our results highlight the importance of including a physical model in NMMs to represent measurements. We provide a framework connecting microscale neuron models with the neural mass formalism and with physical models of the measurement process that can improve the accuracy of predicted electrophysiological recordings.

Uterine activity modifies the response of the fetal autonomic nervous system at preterm active labor.

The autonomic nervous system of preterm fetuses has a different level of maturity than term fetuses. Thus, their autonomic response to transient hypoxemia caused by uterine contractions in labor may differ. This study aims to compare the behavior of the fetal autonomic response to uterine contractions between preterm and term active labor using a novel time-frequency analysis of fetal heart rate variability (FHRV). We performed a case-control study using fetal R-R and uterine activity time series obtained by abdominal electrical recordings from 18 women in active preterm labor (32-36 weeks of gestation) and 19 in active term labor (39-40 weeks of gestation). We analyzed 20 minutes of the fetal R-R time series by applying a Continuous Wavelet Transform (CWT) to obtain frequency (HF, 0.2-1Hz; LF, 0.05-0.2Hz) and time-frequency (Flux0, Flux90, and Flux45) domain features. Time domain FHRV features (SDNN, RMSSD, meanNN) were also calculated. In addition, ultra-short FHRV analysis was performed by segmenting the fetal R-R time series according to episodes of the uterine contraction and quiescent periods. No significant differences between preterm and term labor were found for FHRV features when calculated over 20 minutes. However, we found significant differences when segmenting between uterine contraction and quiescent periods. In the preterm group, the LF, Flux0, and Flux45 were higher during the average contraction episode compared with the average quiescent period (p<0.01), while in term fetuses, vagally mediated FHRV features (HF and RMSSD) were higher during the average contraction episode (p<0.05). The meanNN was lower during the strongest contraction in preterm fetuses compared to their consecutive quiescent period (p=0.008). The average autonomic response to contractions in preterm fetuses shows sympathetic predominance, while term fetuses respond through parasympathetic activity. Comparison between groups during the strongest contraction showed a diminished fetal autonomic response in the preterm group. Thus, separating contraction and quiescent periods during labor allows for identifying differences in the autonomic nervous system cardiac regulation between preterm and term fetuses.

Adaptive coding across visual features during free-viewing and fixation conditions

Theoretical studies have long proposed that adaptation allows the brain to effectively use the limited response range of sensory neurons to encode widely varying natural inputs. However, despite this influential view, experimental studies have exclusively focused on how the neural code adapts to a range of stimuli lying along a single feature axis, such as orientation or contrast. Here, we performed electrical recordings in macaque visual cortex (area V4) to reveal significant adaptive changes in the neural code of single cells and populations across multiple feature axes. Both during free viewing and passive fixation, populations of cells improved their ability to encode image features after rapid exposure to stimuli lying on orthogonal feature axes even in the absence of initial tuning to these stimuli. These results reveal a remarkable adaptive capacity of visual cortical populations to improve network computations relevant for natural viewing despite the modularity of the functional cortical architecture.

Activity-Dependent Non-Coding RNA MAPK Interactome of the Human Epileptic Brain.

The human brain has evolved to have extraordinary capabilities, enabling complex behaviors. The uniqueness of the human brain is increasingly posited to be due in part to the functions of primate-specific, including human-specific, long non-coding RNA (lncRNA) genes, systemically less conserved than protein-coding genes in evolution. Patients who have surgery for drug-resistant epilepsy are subjected to extensive electrical recordings of the brain tissue that is subsequently removed in order to treat their epilepsy. Precise localization of brain tissues with distinct electrical properties offers a rare opportunity to explore the effects of brain activity on gene expression. Here, we identified 231 co-regulated, activity-dependent lncRNAs within the human MAPK signaling cascade. Six lncRNAs, four of which were antisense to known protein-coding genes, were further examined because of their high expression and potential impact on the disease phenotype. Using a model of repeated depolarizations in human neuronal-like cells (Sh-SY5Y), we show that five out of six lncRNAs were electrical activity-dependent, with three of four antisense lncRNAs having reciprocal expression patterns relative to their protein-coding gene partners. Some were directly regulated by MAPK signaling, while others effectively downregulated the expression of the protein-coding genes encoded on the opposite strands of their genomic loci. These lncRNAs, therefore, likely contribute to highly evolved and primate-specific human brain regulatory functions that could be therapeutically modulated to treat epilepsy.

Methods for Paramecium tetraurelia ciliary membrane protein identification and function.

In this chapter we provide some tools to study the ciliary proteins that make it possible for Paramecium cells to swim by beating their cilia. These proteins include many ion channels, accessory proteins, peripheral proteins, structural proteins, rootlets of cilia, and enzymes. Some of these proteins are also found in the soma membrane, but their distinct and critical functions are in the cilia. Paramecium has 4000 or more cilia per cell, giving it an advantage for biochemical studies over cells that have one primarily cilium per cell. Nonetheless, a challenge for studies of many ciliary proteins in Paramecium is their low abundance. We discuss here several strategies to overcome this challenge and other challenges such as working with very large channel proteins. We also include for completeness other techniques that are critical to the study of swimming behavior, such as genetic crosses, recording of swimming patterns, electrical recordings, expression of very large channel proteins, RNA Interference, among others.

GRINtrode: a neural implant for simultaneous two-photon imaging and extracellular electrophysiology in freely moving animals.

In vivo imaging and electrophysiology are powerful tools to explore neuronal function that each offer unique complementary information with advantages and limitations. Capturing both data types from the same neural population in the freely moving animal would allow researchers to take advantage of the capabilities of both modalities and further understand how they relate to each other. Here, we present a head-mounted neural implant suitable for in vivo two-photon imaging of neuronal activity with simultaneous extracellular electrical recording in head-fixed or fiber-coupled freely moving animals. A gradient refractive index (GRIN) lens-based head-mounted neural implant with extracellular electrical recording provided by tetrodes on the periphery of the GRIN lens was chronically implanted. The design of the neural implant allows for recording from head-fixed animals, as well as freely moving animals by coupling the imaging system to a coherent imaging fiber bundle. We demonstrate simultaneous two-photon imaging of GCaMP and extracellular electrophysiology of neural activity in awake head-fixed and freely moving mice. Using the collected information, we perform correlation analysis to reveal positive correlation between optical and local field potential recordings. Simultaneously recording neural activity using both optical and electrical methods provides complementary information from each modality. Designs that can provide such bi-modal recording in freely moving animals allow for the investigation of neural activity underlying a broader range of behavioral paradigms.

A-IGZO thin-film transistors with transparent ultrathin Al/Ag bilayer source and drain for active neural interfaces

Electro-optical neural interface technologies based on transparent electronics have been developed to take advantage of both high spatial resolution of optical cellular imaging by microscopes and high temporal resolution of electrical neural recordings. Recently, active-matrix systems based on amorphous indium gallium zinc oxide (a-IGZO) thin-film transistors (TFTs) have been suggested for high-density electrical neural recordings owing to the high mobility and optical transparency of the IGZO. However, conventional metallic source and drain electrodes forming ohmic contacts with the a-IGZO are the limiting factors of the overall system transparency because the electrodes have substantial portions in the TFT structures. In this work, we propose an ultrathin metal bilayer as the transparent source and drain electrodes of the a-IGZO TFTs for fully transparent TFT-based electro-optical neural interfaces. The ultrathin metal bilayer electrodes consist of 2.5–4.5 nm-thick aluminum as a seed layer and 8 nm-thick silver. The ultrathin Al/Ag bilayer suppressed localized surface plasmonic resonance, showing 40–70% of transmittance in the range of 350–700 nm and thus allowing us to observe cultured neurons through the transparent electrodes. We also confirmed that the ultrathin Al/Ag electrodes form decent ohmic contacts to the IGZO, showing width-normalized contact resistance of 2.9 kΩ-cm which is similar to the previously reported other transparent S/D electrodes. The a-IGZO TFTs with the ultrathin Al/Ag showed the highest linear mobility of 3.9 cm2/Vs of in long channels and 0.2–0.64 cm2/Vs in short channels. The gate-bias normalized cut-off frequency was 8–26 kHz/V at Lch = 20 μm, which would be sufficient for recording a wide range of neural signals.

Ultrasonically actuated neural probes for reduced trauma and inflammation in mouse brain

Electrical neural recordings measured using direct electrical interfaces with neural tissue suffer from a short lifespan because the signal strength decreases over time. The inflammatory response to the inserted microprobe can create insulating tissue over the electrical interfaces, reducing the recorded signal below noise levels. One of the factors contributing to this inflammatory response is the tissue damage caused during probe insertion. Here, we explore the use of ultrasonic actuation of the neural probe during insertion to minimize tissue damage in mice. Silicon neural microprobes were designed and fabricated with integrated electrical recording sites and piezoelectric transducers. The microprobes were actuated at ultrasonic frequencies using integrated piezoelectric transducers. The microprobes were inserted into mouse brains under a glass window over the brain surface to image the tissue surrounding the probe using two-photon microscopy. The mechanical force required to penetrate the tissue was reduced by a factor of 2–3 when the microprobe was driven at ultrasonic frequencies. Tissue histology at the probe insertion site showed a reduced area of damage and decreased microglia counts with increasing ultrasonic actuation of the probes. Two-photon imaging of the microprobe over weeks demonstrated stabilization of the inflammatory response. Recording of electrical signals from neurons over time suggests that microprobes inserted using ultrasound have a higher signal-to-noise ratio over an extended time period.

Electrochemical Testing of a New Polyimide Thin Film Electrode for Stimulation, Recording, and Monitoring of Brain Activity.

Subdural electrode arrays are used for monitoring cortical activity and functional brain mapping in patients with seizures. Until recently, the only commercially available arrays were silicone-based, whose thickness and lack of conformability could impact their performance. We designed, characterized, manufactured, and obtained FDA clearance for 29-day clinical use (510(k) K192764) of a new thin-film polyimide-based electrode array. This study describes the electrochemical characterization undertaken to evaluate the quality and reliability of electrical signal recordings and stimulation of these new arrays. Two testing paradigms were performed: a short-term active soak with electrical stimulation and a 29-day passive soak. Before and after each testing paradigm, the arrays were evaluated for their electrical performance using Electrochemical Impedance Spectroscopy (EIS), Cyclic Voltammetry (CV) and Voltage Transients (VT). In all tests, the impedance remained within an acceptable range across all frequencies. The different CV curves showed no significant changes in shape or area, which is indicative of stable electrode material. The electrode polarization remained within appropriate limits to avoid hydrolysis.

Closed-loop optogenetic control of the dynamics of neural activity in non-human primates.

Electrical neurostimulation is effective in the treatment of neurological disorders, but associated recording artefacts generally limit its applications to open-loop stimuli. Real-time and continuous closed-loop control of brain activity can, however, be achieved by pairing concurrent electrical recordings and optogenetics. Here we show that closed-loop optogenetic stimulation with excitatory opsins enables the precise manipulation of neural dynamics in brain slices from transgenic mice and in anaesthetized non-human primates. The approach generates oscillations in quiescent tissue, enhances or suppresses endogenous patterns in active tissue and modulates seizure-like bursts elicited by the convulsant 4-aminopyridine. A nonlinear model of the phase-dependent effects of optical stimulation reproduced the modulation of cycles of local-field potentials associated with seizure oscillations, as evidenced by the systematic changes in the variability and entropy of the phase-space trajectories of seizures, which correlated with changes in their duration and intensity. We also show that closed-loop optogenetic neurostimulation could be delivered using intracortical optrodes incorporating light-emitting diodes. Closed-loop optogenetic approaches may be translatable to therapeutic applications in humans.

Combining NGN2 programming and dopaminergic patterning for a rapid and efficient generation of hiPSC-derived midbrain neurons

The use of human derived induced pluripotent stem cells (hiPSCs) differentiated to dopaminergic (DA) neurons offers a valuable experimental model to decorticate the cellular and molecular mechanisms of Parkinson’s disease (PD) pathogenesis. However, the existing approaches present with several limitations, notably the lengthy time course of the protocols and the high variability in the yield of DA neurons. Here we report on the development of an improved approach that combines neurogenin-2 programming with the use of commercially available midbrain differentiation kits for a rapid, efficient, and reproducible directed differentiation of hiPSCs to mature and functional induced DA (iDA) neurons, with minimum contamination by other brain cell types. Gene expression analysis, associated with functional characterization examining neurotransmitter release and electrical recordings, support the functional identity of the iDA neurons to A9 midbrain neurons. iDA neurons showed selective vulnerability when exposed to 6-hydroxydopamine, thus providing a viable in vitro approach for modeling PD and for the screening of small molecules with neuroprotective proprieties.

TLR4 pathway induces proarrhythmogenic slow conduction by impaired depolarisation

Abstract Background Cardiac inflammation driven by the Toll-Like-Receptor 4 (TLR4) is correlated to increased risk of arrhythmia. Cardiac arrhythmogenesis and the formation of re-entry tachycardia is highly dependent on conduction velocity (CV) and action potential (AP) duration (APD). As TLR4 induced APD shortening has been shown, we analyze in this study for the first time the TLR4 effect on conductance disturbances in a LPS induced septic mouse model. Methods Systemic activation of TLR4 in mice was achieved by intraperitoneal LPS injection 3.5 hours prior to experiments. In vivo electrophysiological investigation (EPI) was performed using an octapolar transvenous catheter placed to the right heart. Ex vivo experiments were performed on Langendorff-perfused hearts. AP propagation was measured by optical voltage mapping (OVM) with voltage sensitive dye Di-4-ANEPPS. For AP analysis including RMP, intracellular electrical recordings were performed using sharp microelectrodes. Wildtype mice after LPS injection were compared to wildtype mice after vehicle (NaCl) injection or ubiquitous TLR4 knockout (TLR4−/−) mice with LPS or vehicle application. Results In vivo EPI showed a tendency to more atrial fibrillation after LPS injection (+LPS 5/6, +NaCl 2/6, p=0.2). Ventricular stimulation evoked ventricular tachycardia in every LPS treated WT mouse but less in controls (+LPS 6/6, +NaCl 1/6, p=0.01). OVM measured decreased CV in both atria and ventricle after LPS treatment (atria: +LPS: 43.1±3.1cm/s, n=5; +NaCl: 72.6±9.8cm/s, n=10, p=0.04; ventricle: +LPS: 50.2±2.2cm/s, n=6; +NaCl: 67.7±5.0cm/s, n=10, p=0.02). In analysis of AP in atria upstroke velocity was slightly decreased (max.dV/dt: +LPS: 123.1±4.8V/s, n=22; +NaCl: 158.5±5.3V/s, n=39, p=0.04) but highly reduced in ventricle (max.dV/dt: +LPS: 91.8±3.6V/s, n=27; +NaCl: 140.7±6.3V/s, n=35, p&amp;lt;0.0001). RMP in atria was depolarised after LPS injection (+LPS: −70.1±1.9mV, n=22; +NaCl: −81.1±1.2mV, n=39, p=0.004) explaining decreased upstroke velocity and CV slowing in atria by voltage-dependent Na+ channel inactivation. Ventricular RMP was unaffected by LPS injection (+LPS: −75.1±1.1mV, n=44; +NaCl: −76.3±0.9mV, n=55, p=0.83). Therefore the Na+ currents were measured in isolated ventricular cardiomyocytes using whole cell patch clamp revealing the maximum Na+ current density lowered after LPS treatment (+LPS: −20.6±1.7 pA/pF, n=16, +NaCl 27.1±2.6 pA/pF, n=10, p=0.03). LPS did not affect EPI, CV, upstroke velocity or current density in TLR4−/− mice. Conclusion Herein we report for the first time impaired cardiac depolarisation and conduction after short term activation of TLR4 in vivo. Pro arrhythmogenic mechanisms differ in atria and ventricle: Increased atrial RMP inactivates Na+ current leading to reduction of CV. Ventricular slow CV is caused by reduced current density of Na+ channels. This different TLR4 effect might be important for novel antiarrhythmic and antiinflammatory applications. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): GEROK-grant, University Bonn

E-Cannula reveals anatomical diversity in sharp-wave ripples as a driver for the recruitment of distinct hippocampal assemblies.

The hippocampus plays a critical role in spatial navigation and episodic memory. However, research on invivo hippocampal activity dynamics mostly relies on single modalities, such as electrical recordings or optical imaging, with respectively limited spatial and temporal resolution. Here, we develop the E-Cannula, integrating fully transparent graphene microelectrodes with imaging cannula, which enables simultaneous electrical recording and two-photon calcium imaging from the exact same neural populations across an anatomically extended region of the mouse hippocampal CA1 stably across several days. The large-scale multimodal recordings show that sharp wave ripples (SWRs) exhibit spatiotemporal wave patterns along multiple axes in two-dimensional (2D) space with different spatial extents and temporal propagation modes. Notably, distinct SWR wave patterns are associated with the selective recruitment of orthogonal CA1 cell assemblies. These results demonstrate the utility of the E-Cannula as a versatile neurotechnology with the potential for future integration with other optical components.

High-fidelity dendritic sodium spike generation in human layer 2/3 neocortical pyramidal neurons.

Dendritic spikes function as cardinal components of rodent neocortical circuit computations. Recently, the biophysical properties of human pyramidal neurons (PNs) have been reported to be divergent, raising the question of whether dendritic spikes have homologous roles in the human neocortex. To directly address this, we made electrical recordings from the soma and apical dendrites of human and rat layer 2/3 PNs of the temporal cortex. In both species, dendritic excitatory input led to the initiation of sodium-channel-mediated dendritic spikes. Dendritic sodium spikes could be generated across a wide input range, exhibited a similar frequency range of activation, and forward-propagated with high-fidelity to implement stereotyped computations in human and rat PNs. However, the physical expansion and complexification of the apical dendritic trees of human PNs allowed the enriched expression of dendritic spike generation. The computational capacity of human PNs is therefore enhanced by the widespread implementation of a conserved dendritic integration mechanism.

Multilayer CVD graphene electrodes using a transfer-free process for the next generation of optically transparent and MRI-compatible neural interfaces.

Multimodal platforms combining electrical neural recording and stimulation, optogenetics, optical imaging, and magnetic resonance (MRI) imaging are emerging as a promising platform to enhance the depth of characterization in neuroscientific research. Electrically conductive, optically transparent, and MRI-compatible electrodes can optimally combine all modalities. Graphene as a suitable electrode candidate material can be grown via chemical vapor deposition (CVD) processes and sandwiched between transparent biocompatible polymers. However, due to the high graphene growth temperature (≥ 900 °C) and the presence of polymers, fabrication is commonly based on a manual transfer process of pre-grown graphene sheets, which causes reliability issues. In this paper, we present CVD-based multilayer graphene electrodes fabricated using a wafer-scale transfer-free process for use in optically transparent and MRI-compatible neural interfaces. Our fabricated electrodes feature very low impedances which are comparable to those of noble metal electrodes of the same size and geometry. They also exhibit the highest charge storage capacity (CSC) reported to date among all previously fabricated CVD graphene electrodes. Our graphene electrodes did not reveal any photo-induced artifact during 10-Hz light pulse illumination. Additionally, we show here, for the first time, that CVD graphene electrodes do not cause any image artifact in a 3T MRI scanner. These results demonstrate that multilayer graphene electrodes are excellent candidates for the next generation of neural interfaces and can substitute the standard conventional metal electrodes. Our fabricated graphene electrodes enable multimodal neural recording, electrical and optogenetic stimulation, while allowing for optical imaging, as well as, artifact-free MRI studies.

Optrode Array for Simultaneous Optogenetic Modulation and Electrical Neural Recording.

During the last decade, optogenetics has become an essential tool for the investigation of neural signaling due to its unique capability of selective neural modulation or monitoring. As specific types of neuronal cells can be genetically modified to express opsin proteins, optogenetics enables optical stimulation or inhibition of the selected neurons. There have been several technological advances in the optical system for optogenetics. Recently, it was proposed to combine the optical waveguide for light delivery with electrophysiological recording to simultaneously monitor the neural responses to optogenetic stimulation or inhibition. In this study, an implantable optrode array (2x2 optical fibers) was developed with embedded multichannel electrodes. A light-emitting diode (LED) was employed as a light source, and a microfabricated microlens array was integrated to provide sufficient light power at the tip of the optical fibers. The optrode array system comprises the disposable part and the reusable part. The disposable part has optical fibers and electrodes, while the reusable part has the LED and electronic circuitry for light control and neural signal processing. The novel design of the implantable optrode array system is introduced in the accompanying video in addition to the procedure of the optrode implantation surgery, optogenetic light stimulation, and the electrophysiological neural recording. The results of in vivo experiments successfully showed time-locked neural spikes evoked by the light stimuli from hippocampal excitatory neurons of mice.