Carbon fiber electrodes for intracellular recording and stimulation

Objective. To understand neural circuit dynamics, it is critical to manipulate and record many individual neurons. Traditional recording methods, such as glass microelectrodes, can only control a small number of neurons. More recently, devices with high electrode density have been developed, but few of them can be used for intracellular recording or stimulation in intact nervous systems. Carbon fiber electrodes (CFEs) are 8 micron-diameter electrodes that can be assembled into dense arrays (pitches ≥ 80 µm). They have good signal-to-noise ratios (SNRs) and provide stable extracellular recording both acutely and chronically in neural tissue in vivo (e.g., rat motor cortex). The small fiber size suggests that arrays could be used for intracellular stimulation. Approach. We tested CFEs for intracellular stimulation using the large identified and electrically compact neurons of the marine mollusk Aplysia californica. Neuron cell bodies in Aplysia range from 30 µm to over 250 µm. We compared the efficacy of CFEs to glass microelectrodes by impaling the same neuron’s cell body with both electrodes and connecting them to a DC coupled amplifier. Main Results. We observed that intracellular waveforms were essentially identical, but the amplitude and SNR in the CFE were lower than in the glass microelectrode. CFE arrays could record from 3 to 8 neurons simultaneously for many hours, and many of these recordings were intracellular, as shown by simultaneous glass microelectrode recordings. CFEs coated with platinum-iridium could stimulate and had stable impedances over many hours. CFEs not within neurons could record local extracellular activity. Despite the lower SNR, the CFEs could record synaptic potentials. CFEs were less sensitive to mechanical perturbations than glass microelectrodes. Significance. The ability to do stable multi-channel recording while stimulating and recording intracellularly make CFEs a powerful new technology for studying neural circuit dynamics.

Synbiotics Containing Nanoprebiotics: A Novel Therapeutic Strategy to Restore Gut Dysbiosis

A new formulation, nanoprebiotics [e.g., phthalyl pullulan nanoparticles (PPNs)], was demonstrated to enhance the antimicrobial activity of probiotics [e.g., Lactobacillus plantarum (LP)] in vitro through intracellular stimulation better than that by backbone prebiotics, which are commonly used. In this study, we aimed to investigate whether this combination would exert distinct effects as synbiotics in vivo. Synbiotics combinations of LP, pullulan, and PPNs were used as experimental treatments in a dysbiosis-induced murine model, and their restorative effect was assessed using pathogen Escherichia coli K99 challenge. Our results showed that the E. coli infection was suppressed markedly in the experimental group fed with synbiotics containing PPNs. In addition, the decrease in serum endotoxin level after synbiotics treatment suggested the reinforcement of the gut barrier. Comparison of treatment groups, including a normal control group, showed that synbiotics containing PPNs increased microbial diversity, which is a representative parameter of healthy status. Furthermore, distinct from probiotics treatment alone, synbiotics showed additive effects of enrichment of several well-known beneficial bacteria such as Lactobacillus, Bifidobacterium, and other butyrate-producing bacteria including Faecalibacterium. Collectively, our results indicate that synbiotics containing PPNs are effective at restoring gut dysbiosis, suppressing pathogenic infection, and increasing microbial diversity, suggesting that synbiotics with nanoprebiotics have the potential to be a novel strategy for ameliorating gut dysbiosis and infectious diseases.

Synbiotics containing nanoprebiotics: a novel therapeutic strategy to restore gut dysbiosis

Background: In our previous study, it was demonstrated that nanoprebiotics, phthalyl pullulan nanoparticles (PPNs), a new formulation enhanced the antimicrobial activity of probiotics Lactobacillus plantarum (LP) in vitro by intracellular stimulation more than backbone prebiotics generally used by far. In this study, we aimed to investigate whether this combination may exert a distinguished effect as synbiotics in vivo. To accomplish this goal, the synbiotics combination of LP, pullulan, and PPNs were treated to a dysbiosis-induced mouse model and assessed their restoring effect using pathogen Escherichia coli K99 (EC) challenge. Results: The experiment group fed with synbiotics containing PPNs more suppressed the infection of EC in mice and reinforced the gut barrier by proving the decreased serum endotoxin level. Also, the synbiotics containing PPNs increased microbial diversity as a representative parameter of healthy status compared with other groups, including a normal control group. Furthermore, distinct from treated probiotics alone, the synbiotics showed additive effects to enrich several well-known beneficial bacteria such as Lactobacillus, Bifidobacterium, and several butyrate-producing bacteria including Faecalibacterium. Conclusion: Our results indicated that synbiotics containing PPNs are very effective at restoring gut dysbiosis and suppressing pathogenic infection with an increase in microbial diversity, suggesting that the synbiotics with nanoprebiotics have the potential to be a novel strategy for curing gut dysbiosis and infectious diseases.

Multifunctional single-drug loaded nanoparticles for enhanced cancer treatment with low toxicity in vivo

After nanoparticles internalized, active oxaliplatin(ii) and DMC can be released upon UVA and intracellular stimulation, exhibiting enhanced anti-cancer efficacy.

Strength–Duration Relationship for Extracellular Neural Stimulation: Numerical and Analytical Models

The strength–duration relationship for extracellular stimulation is often assumed to be similar to the classical intracellular stimulation model, with a slope asymptotically approaching 1/τ at pulse durations shorter than chronaxy. We modeled extracellular neural stimulation numerically and analytically for several cell shapes and types of active membrane properties. The strength–duration relationship was found to differ significantly from classical intracellular models. At pulse durations between 4 μs and 5 ms stimulation is dominated by sodium channels, with a slope of −0.72 in log-log coordinates for the Hodgkin–Huxley ion channel model. At shorter durations potassium channels dominate and slope decreases to −0.13. Therefore the charge per phase is decreasing with decreasing stimulus duration. With pulses shorter than cell polarization time (∼0.1–1 μs), stimulation is dominated by polarization dynamics with a classical −1 slope and the charge per phase becomes constant. It is demonstrated that extracellular stimulation can have not only lower but also upper thresholds and may be impossible below certain pulse durations. In some regimes the extracellular current can hyperpolarize cells, suppressing rather than stimulating spiking behavior. Thresholds for burst stimuli can be either higher or lower than that of a single pulse, depending on pulse duration. The modeled thresholds were found to be comparable to published experimental data. Electroporation thresholds, which limit the range of safe stimulation, were found to exceed stimulation thresholds by about two orders of magnitude. These results provide a biophysical basis for understanding stimulation dynamics and guidance for optimizing the neural stimulation efficacy and safety.

LINEAR AND NONLINEAR PROPERTIES OF PRESTIMULUS VENTRAL CORD SIGNALS DISTINGUISH SWIMMING RESPONSE OF THE LEECH TO INTRACELLULAR STIMULATION

Stimulation of a trigger interneuron of an isolated nerve cord preparation of the medicinal leech, Hirudo medicinalis, sometimes leads to swimming; sometimes it does not. The known synaptic interactions in the swim-initiating pathway do not adequately explain the observed behavioral variability. We investigate signals propagating in the ventral cord and show that, (i) prior to stimulation, the standard deviation of the signals that precede swimming (TS) is greater than that of the signals that do not (NS), (ii) linear correlations of NS signals are indistinguishable from those of TS signals, (iii) nonlinear correlations measured by mutual information of time-delayed epochs of TS signals are greater than those of NS signals, and (iv) for small time differences, the mutual information of time-delayed epochs of NS and TS signals are different from surrogates that have the same cross-correlations but are otherwise random.