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Highly stretchable and customizable microneedle electrode arrays for intramuscular electromyography.Science Advances May 2024Stretchable three-dimensional (3D) penetrating microelectrode arrays have potential utility in various fields, including neuroscience, tissue engineering, and wearable...
Stretchable three-dimensional (3D) penetrating microelectrode arrays have potential utility in various fields, including neuroscience, tissue engineering, and wearable bioelectronics. These 3D microelectrode arrays can penetrate and conform to dynamically deforming tissues, thereby facilitating targeted sensing and stimulation of interior regions in a minimally invasive manner. However, fabricating custom stretchable 3D microelectrode arrays presents material integration and patterning challenges. In this study, we present the design, fabrication, and applications of stretchable microneedle electrode arrays (SMNEAs) for sensing local intramuscular electromyography signals ex vivo. We use a unique hybrid fabrication scheme based on laser micromachining, microfabrication, and transfer printing to enable scalable fabrication of individually addressable SMNEA with high device stretchability (60 to 90%). The electrode geometries and recording regions, impedance, array layout, and length distribution are highly customizable. We demonstrate the use of SMNEAs as bioelectronic interfaces in recording intramuscular electromyography from various muscle groups in the buccal mass of .
Topics: Electromyography; Needles; Microelectrodes; Animals; Equipment Design; Electrodes; Muscle, Skeletal; Humans
PubMed: 38691612
DOI: 10.1126/sciadv.adn7202 -
Scandinavian Journal of Pain Jan 2024Although the relationship between traumatic experiences (TEs) and psychosomatic manifestations (pain, somatization, somatosensory amplification [SSA], and alexithymia)...
OBJECTIVES
Although the relationship between traumatic experiences (TEs) and psychosomatic manifestations (pain, somatization, somatosensory amplification [SSA], and alexithymia) has been widely described, very few studies have investigated how these variables correlate with each other and with a history of TEs. The aim of this study was to investigate whether and how current psychosomatic manifestations are correlated with major and minor adult- and childhood TEs.
METHODS
One hundred and forty-six patients (91 with pain) from the Pisa Gift Institute for Integrative Medicine Psychosomatics Lab., Italy, were assessed for pain, history of TEs (divided into major and minor based on whether or not they meet the DSM-5 Criterion A for post-traumatic stress disorder), alexithymia, somatization, and SSA.
RESULTS
TEs were positively correlated with age, the sensorial dimension and intensity of pain, somatization, psychopathology index, SSA, and alexithymia. Using the somatization score (controlled for age) as a covariate, the previous correlations between psychosomatic dimensions and TEs lost their statistical significance: SSA (total TEs: from = 0.30, = 0.000 to = -0.04, = 0.652); alexithymia (total TEs: from = 0.28, = 0.001 to = 0.04, = 0.663); sensorial dimension of pain (total TEs: from = 0.30, = 0.015 to = 0.12, = 0.373); and pain intensity (total TEs: from = 0.38, = 0.004 to = -0.15, = 0.317). Interestingly, the tendency to report more intense pain was mainly predicted by minor TEs in childhood ( = 0.28; = 0.030).
CONCLUSIONS
The number of lifetime TEs is positively correlated with the sensorial dimension and intensity of pain but not its affective and cognitive dimensions. However, the former relationship depends on the presence of somatization. The intensity of pain is associated with minor rather than major TEs, especially when they occur in childhood.
Topics: Humans; Male; Female; Affective Symptoms; Adult; Middle Aged; Somatoform Disorders; Psychophysiologic Disorders; Pain; Stress Disorders, Post-Traumatic; Young Adult; Aged; Italy
PubMed: 38661113
DOI: 10.1515/sjpain-2023-0102 -
The Journal of Experimental Biology Apr 2024The mechanical forces experienced during movement and the time constants of muscle activation are important determinants of the durations of behaviours, which may both...
The mechanical forces experienced during movement and the time constants of muscle activation are important determinants of the durations of behaviours, which may both be affected by size-dependent scaling. The mechanics of slow movements in small animals are dominated by elastic forces and are thus quasistatic (i.e. always near mechanical equilibrium). Muscular forces producing movement and elastic forces resisting movement should scale identically (proportional to mass2/3), leaving the scaling of the time constant of muscle activation to play a critical role in determining behavioural duration. We tested this hypothesis by measuring the duration of feeding behaviours in the marine mollusc Aplysia californica whose body sizes spanned three orders of magnitude. The duration of muscle activation was determined by measuring the time it took for muscles to produce maximum force as A. californica attempted to feed on tethered inedible seaweed, which provided an in vivo approximation of an isometric contraction. The timing of muscle activation scaled with mass0.3. The total duration of biting behaviours scaled identically, with mass0.3, indicating a lack of additional mechanical effects. The duration of swallowing behaviour, however, exhibited a shallower scaling of mass0.17. We suggest that this was due to the allometric growth of the anterior retractor muscle during development, as measured by micro-computed tomography (micro-CT) scans of buccal masses. Consequently, larger A. californica did not need to activate their muscles as fully to produce equivalent forces. These results indicate that muscle activation may be an important determinant of the scaling of behavioural durations in quasistatic systems.
Topics: Animals; Aplysia; X-Ray Microtomography; Muscles; Feeding Behavior; Deglutition
PubMed: 38584490
DOI: 10.1242/jeb.246551 -
ENeuro Apr 2024Long-term sensitization in is accompanied by a persistent up-regulation of mRNA encoding the peptide neurotransmitter Phe-Met-Arg-Phe-amide (FMRFa), a neuromodulator...
Long-term sensitization in is accompanied by a persistent up-regulation of mRNA encoding the peptide neurotransmitter Phe-Met-Arg-Phe-amide (FMRFa), a neuromodulator that opposes the expression of sensitization through activation of the arachidonic acid second-messenger pathway. We completed a preregistered test of the hypothesis that FMRFa plays a critical role in the forgetting of sensitization. received long-term sensitization training and were then given whole-body injections of vehicle (= 27), FMRFa (= 26), or 4-bromophenacylbromide (4-BPB; = 31), a phospholipase inhibitor that prevents the release of arachidonic acid. FMRFa produced no changes in forgetting. 4-BPB decreased forgetting measured 6 d after training [ = 0.55 95% CI(0.01, 1.09)], though the estimated effect size is uncertain. Our results provide preliminary evidence that forgetting of sensitization may be a regulated, active process in , but could also indicate a role for arachidonic acid in stabilizing the induction of sensitization.
Topics: Animals; Arachidonic Acid; Aplysia
PubMed: 38538086
DOI: 10.1523/ENEURO.0516-23.2024 -
Scientific Reports Mar 2024Magnetic fields are widely used for neuromodulation in clinical settings. The intended effect of magnetic stimulation is that neural activity resumes its pre-stimulation...
Magnetic fields are widely used for neuromodulation in clinical settings. The intended effect of magnetic stimulation is that neural activity resumes its pre-stimulation state right after stimulation. Many theoretical and experimental works have focused on the cellular and molecular basis of the acute neural response to magnetic field. However, effects of magnetic stimulation can still last after the termination of the magnetic stimulation (named "carry-over effects"), which could generate profound effects to the outcome of the stimulation. However, the cellular and molecular mechanisms of carry-over effects are largely unknown, which renders the neural modulation practice using magnetic stimulation unpredictable. Here, we investigated carry-over effects at the cellular level, using the combination of micro-magnetic stimulation (µMS), electrophysiology, and computation modeling. We found that high frequency magnetic stimulation could lead to immediate neural inhibition in ganglion neurons from Aplysia californica, as well as persistent, carry-over inhibition after withdrawing the magnetic stimulus. Carry-over effects were found in the neurons that fired action potentials under a variety of conditions. The carry-over effects were also observed in the neurons when the magnetic field was applied across the ganglion sheath. The state of the neuron, specifically synaptic input and membrane potential fluctuation, plays a significant role in generating the carry-over effects after magnetic stimulation. To elucidate the cellular mechanisms of such carry-over effects under magnetic stimulation, we simulated a single neuron under magnetic stimulation with multi-compartment modeling. The model successfully replicated the carry-over effects in the neuron, and revealed that the carry-over effect was due to the dysfunction of the ion channel dynamics that were responsible for the initiation and sustaining of membrane excitability. A virtual voltage-clamp experiment revealed a compromised Na conductance and enhanced K conductance post magnetic stimulation, rendering the neurons incapable of generating action potentials and, therefore, leading to the carry over effects. Finally, both simulation and experimental results demonstrated that the carry-over effects could be controlled by disturbing the membrane potential during the post-stimulus inhibition period. Delineating the cellular and ion channel mechanisms underlying carry-over effects could provide insights to the clinical outcomes in brain stimulation using TMS and other modalities. This research incentivizes the development of novel neural engineering or pharmacological approaches to better control the carry-over effects for optimized clinical outcomes.
Topics: Neurons; Membrane Potentials; Action Potentials; Ion Channels; Magnetic Phenomena; Electric Stimulation
PubMed: 38431662
DOI: 10.1038/s41598-024-55915-8 -
Molecular Biology of the Cell Apr 2024Neuronal growth cones sense a variety of cues including chemical and mechanical ones to establish functional connections during nervous system development....
Neuronal growth cones sense a variety of cues including chemical and mechanical ones to establish functional connections during nervous system development. Substrate-cytoskeletal coupling is an established model for adhesion-mediated growth cone advance; however, the detailed molecular and biophysical mechanisms underlying the mechanosensing and mechanotransduction process remain unclear. Here, we adapted a motor-clutch model to better understand the changes in clutch and cytoskeletal dynamics, traction forces, and substrate deformation when a growth cone interacts with adhesive substrates of different stiffnesses. Model parameters were optimized using experimental data from growth cones probed with force-calibrated glass microneedles. We included a reinforcement mechanism at both motor and clutch level. Furthermore, we added a threshold for retrograde F-actin flow that indicates when the growth cone is strongly coupled to the substrate. Our modeling results are in strong agreement with experimental data with respect to the substrate deformation and the latency time after which substrate-cytoskeletal coupling is strong enough for the growth cone to advance. Our simulations show that it takes the shortest time to achieve strong coupling when substrate stiffness was low at 4 pN/nm. Taken together, these results suggest that growth cones respond faster and more efficiently to soft than stiff substrates.
Topics: Growth Cones; Mechanotransduction, Cellular; Actins; Cytoskeleton; Retinal Cone Photoreceptor Cells
PubMed: 38354034
DOI: 10.1091/mbc.E23-09-0364 -
Journal of Neuroscience Methods Apr 2024To study neural control of behavior, intracellular recording and stimulation of many neurons in freely moving animals would be ideal. However, current technologies limit...
BACKGROUND
To study neural control of behavior, intracellular recording and stimulation of many neurons in freely moving animals would be ideal. However, current technologies limit the number of neurons that can be monitored and manipulated. A new technology has become available for intracellular recording and stimulation which we demonstrate in the tractable nervous system of Aplysia.
NEW METHOD
Carbon fiber electrode arrays (whose tips are coated with platinum-iridium) were used with an in vitro feeding preparation to intracellularly record from and to control the activity of multiple neurons during feeding movements.
RESULTS
In an in vitro feeding preparation, the carbon fiber electrode arrays recorded action potentials and subthreshold synaptic potentials during feeding movements. Depolarizing or hyperpolarizing currents activated or inhibited identified neurons (respectively), manipulating the movements of the feeding apparatus.
COMPARISON WITH EXISTING METHOD(S)
Standard glass microelectrodes that are commonly used for intracellular recording are stiff, liable to break in response to movement, and require many micromanipulators to be precisely positioned. In contrast, carbon fiber arrays are less sensitive to movement, but are capable of multiple channels of intracellular recording and stimulation.
CONCLUSIONS
Carbon fiber arrays are a novel technology for intracellular recording that can be used in moving preparations. They can record both action potentials and synaptic activity in multiple neurons and can be used to stimulate multiple neurons in complex patterns.
Topics: Animals; Carbon Fiber; Aplysia; Neurons; Microelectrodes; Action Potentials
PubMed: 38336092
DOI: 10.1016/j.jneumeth.2024.110077 -
PloS One 2024Many soft-bodied animals have extensive peripheral nervous systems (PNS) with significant sensory roles. One such, the sea slug Pleurobranchaea californica, uses PNS...
Many soft-bodied animals have extensive peripheral nervous systems (PNS) with significant sensory roles. One such, the sea slug Pleurobranchaea californica, uses PNS computations in its chemotactile oral veil (OV) in prey tracking, averaging olfactory stimuli across the OV to target likely source direction, or "stimulus place". This suggests a peripheral subepithelial network (SeN) interconnecting sensory sites to compute the directional average. We pursued anatomy and connectivity of previously described ciliated putative sensory cells on OV papillae. Scanning electron microscopy (SEM) confirmed paddle-shaped cilia in clusters. Anti-tubulin and phalloidin staining showed connections to branching nervelets and muscle fibers for contraction and expansion of papillae. Ciliary cell processes could not be traced into nerves, consistent with sensory transmission to CNS via secondary afferents. Anti-tyrosine hydroxylase-stained ciliated cells in clusters and revealed an at least partially dopaminergic subepithelial network interconnecting clusters near and distant, connections consistent with PNS averaging of multiple stimulated loci. Other, unidentified, SeN neurotransmitters are likely. Confirming chemotactile functions, perfusible suction electrodes recorded ciliary spiking excited by both mechanical and appetitive chemical stimuli. Stimuli induced sensory nerve spiking like that encoding stimulus place. Sensory nerve spikes and cilia cluster spikes were not identifiable as generated by the same neurons. Ciliary clusters likely drive the sensory nerve spikes via SeN, mediating appetitive and stimulus place codes to CNS. These observations may facilitate future analyses of the PNS in odor discrimination and memory, and also suggest such SeNs as potential evolutionary precursors of CNS place-coding circuitry in the segmented, skeletonized protostomes and deuterostomes.
Topics: Animals; Pleurobranchaea; Peripheral Nervous System; Neurons; Aplysia; Predatory Behavior
PubMed: 38329975
DOI: 10.1371/journal.pone.0296872 -
Biological Psychiatry Global Open... Jan 2024Learning requires the activation of protein kinases with distinct temporal dynamics. In , nonassociative learning can be enhanced by a computationally designed learning...
BACKGROUND
Learning requires the activation of protein kinases with distinct temporal dynamics. In , nonassociative learning can be enhanced by a computationally designed learning protocol with intertrial intervals (ITIs) that maximize the interaction between fast-activated PKA (protein kinase A) and slow-activated ERK (extracellular signal-regulated kinase). Whether a similar strategy can enhance associative learning in mammals is unknown.
METHODS
We simulated 1000 training protocols with varying ITIs to predict an optimal protocol based on empirical data for PKA and ERK dynamics in rat hippocampus. Adult male rats received the optimal protocol or control protocols in auditory fear conditioning and fear extinction experiments. Immunohistochemistry was performed to evaluate pCREB (phosphorylated cAMP response element binding)\protein levels in brain regions that have been implicated in fear acquisition.
RESULTS
Rats exposed to the optimal conditioning protocol with irregular ITIs exhibited impaired extinction memory acquisition within the session using a standard footshock intensity, and stronger fear memory retrieval and spontaneous recovery with a weaker footshock intensity, compared with rats that received massed or spaced conditioning protocols with fixed ITIs. Rats exposed to the optimal extinction protocol displayed improved extinction of contextual fear memory and reduced spontaneous recovery compared with rats that received standard extinction protocols. Moreover, the optimal conditioning protocol increased pCREB levels in the dentate gyrus of the dorsal hippocampus, suggesting enhanced induction of long-term potentiation.
CONCLUSIONS
These findings demonstrate that a computational model-driven behavioral intervention can enhance associative learning in mammals and may provide insight into strategies to improve cognition in humans.
PubMed: 38298784
DOI: 10.1016/j.bpsgos.2023.07.006 -
IEEE Transactions on Neural Systems and... 2024Multielectrode arrays for interfacing with neurons are of great interest for a wide range of medical applications. However, current electrodes cause damage over time....
Multielectrode arrays for interfacing with neurons are of great interest for a wide range of medical applications. However, current electrodes cause damage over time. Ultra small carbon fibers help to address issues but controlling the electrode site geometry is difficult. Here we propose a methodology to create small, pointed fiber electrodes (SPFe). We compare the SPFe to previously made blowtorched fibers in characterization. The SPFe result in small site sizes [Formula: see text] with consistently sharp points (20.8 ± 7.64°). Additionally, these electrodes were able to record and/or stimulate neurons multiple animal models including rat cortex, mouse retina, Aplysia ganglia and octopus axial cord. In rat cortex, these electrodes recorded significantly higher peak amplitudes than the traditional blowtorched fibers. These SPFe may be applicable to a wide range of applications requiring a highly specific interface with individual neurons.
Topics: Mice; Rats; Animals; Carbon Fiber; Electrodes, Implanted; Electrodes; Neurons; Cerebral Cortex
PubMed: 38294928
DOI: 10.1109/TNSRE.2024.3360866