Search Results (53)

Microglia and macrophages are critical immune cells within the central nervous system (CNS), with distinct roles in development, homeostasis, and disease. Once viewed as passive bystanders, these cells are now recognized for their dynamic phenotypic plasticity, which enables them to respond to a wide range of physiological and pathological stimuli. During homeostasis, microglia and CNS-resident macrophages actively participate in synaptic pruning, neuronal support, myelin regulation, and immune surveillance, contributing to CNS integrity. However, under pathological conditions, these cells can adopt neurotoxic phenotypes, exacerbating neuroinflammation, oxidative stress, and neuronal damage in diseases such as Alzheimer’s, Parkinson’s, multiple sclerosis, and glioblastoma. This review synthesizes emerging insights into the molecular, epigenetic, and metabolic mechanisms that govern the behavior of microglia and macrophages, highlighting their developmental origins, niche-specific programming, and interactions with other CNS cells. We also explore novel therapeutic strategies aimed at modulating these immune cells to restore CNS homeostasis, including nanotechnology-based approaches for selective targeting, reprogramming, and imaging. Understanding the complex roles of microglia and macrophages in both health and disease is crucial for the development of precise therapies targeting neuroimmune interfaces. Continued advances in single-cell technologies and nanomedicine are paving the way for future therapeutic interventions in neurological disorders. Full article

In a biological nervous system, neurons are connected to each other via synapses to transmit information. Synaptic crosstalk is the phenomenon of mutual interference or interaction of neighboring synapses between neurons. This phenomenon is prevalent in biological neural networks and has an important impact on the function and information processing of the neural system. In order to simulate and study this phenomenon, this paper proposes a memristor model based on hyperbolic tangent function for simulating the activation function of neurons, and constructs a three-neuron HNN model by coupling two memristors, which brings it close to the real behavior of biological neural networks, and provides a new tool for studying complex neural dynamics. The intricate nonlinear dynamics of the MHNN are examined using techniques like Lyapunov exponent analysis and bifurcation diagrams. The viability of the MHNN is confirmed through both analog circuit simulation and FPGA implementation. Moreover, an image encryption approach based on the chaotic system and a dynamic key generation mechanism are presented, highlighting the potential of the MHNN for real-world applications. The histogram shows that the encryption algorithm is effective in destroying the features of the original image. According to the sensitivity analysis, the bit change rate of the key is close to 50% when small perturbations are applied to each of the three parameters of the system, indicating that the system is highly resistant to differential attacks. The findings indicate that the MHNN displays a wide range of dynamical behaviors and high sensitivity to initial conditions, making it well-suited for applications in neuromorphic computing and information security. Full article

The advancement of autonomous vehicles has shifted from modular pipeline architectures to end-to-end frameworks, enabling direct learning of control policies from sensory inputs. While frame-based RGB cameras are commonly utilized, they face challenges in dynamic environments, such as motion blur and varying illumination. Alternatively, event-based cameras, with their high temporal resolution and wide dynamic range, offer a promising solution. However, existing end-to-end models for event camera inputs are primarily constructed using traditional convolutional networks and time-sequence models (e.g., Recurrent Neural Networks, RNNs), which suffer from large parameter counts and excessive redundant computations. To address this gap, we propose LiS-Net, a novel framework that incorporates brain-inspired neural networks to construct the overall architecture, applying it to the task of end-to-end steering prediction. The core of LiS-Net is a liquid neural network, which is designed to simulate the behavior of C. elegans neurons for modeling purposes. By leveraging the strengths of event cameras and brain-inspired computation, LiS-Net achieves superior accuracy, smoothness, and efficiency. Specifically, LiS-Net outperforms existing models with the lowest RMSE and MAE, indicating better accuracy, while also maintaining the fewest number of neurons and achieving competitive FLOPs results, showcasing its computational efficiency. Experiments on the simulated EventScape dataset demonstrate its robustness, while validation on our self-collected dataset showcases its generalization capability. We also release the collected dataset comprising synchronized event cameras, RGB cameras, and GPS and CAN data. LiS-Net lays the foundation for scalable and efficient autonomous driving solutions by integrating bio-inspired sensors with brain-inspired computation. Full article

Background and Objectives: Docosahexaenoic acid (DHA) has been shown to modulate various voltage-gated ion channels and both excitatory and inhibitory synapses. Nonetheless, its exact effect on nociceptive signaling in the trigeminal system has yet to be elucidated. The purpose of the current investigation was to assess if acute DHA given intravenously to rats diminished the excitability of wide dynamic range spinal trigeminal nucleus caudalis (SpVc) neurons in response to mechanical stimulation in vivo. Methods: Single-unit extracellular activity was recorded from SpVc neurons in response to mechanical stimulation of the whisker pad in anesthetized rats. Responses to both non-noxious and noxious mechanical stimuli were analyzed in the present study. Results: The mean firing frequency of SpVc wide dynamic range neurons in response to both non-noxious and noxious mechanical stimuli was significantly dose-dependently inhibited by DHA, and the effect was seen within 5 min. After approximately 20 min, the inhibiting effects dissipated. Conclusions: These results suggest that, in the absence of inflammatory or neuropathic pain, the acute intravenous administration of DHA reduces the activity of trigeminal sensory neurons, including those responsible for pain, indicating that DHA could be utilized as an adjunct and alternative therapeutic agent for managing trigeminal nociceptive pain, including hyperalgesia. Full article

While the modulation of the excitatory and inhibitory neuronal transmission by the phytochemical flavonoid, myricetin (MYR), has been noted in the nervous system, the way in which MYR affects the excitability of nociceptive sensory neurons in vivo remains to be established. This study aimed to explore whether administering MYR intravenously, in acute doses, to rats, diminishes the excitability of SpVc wide-dynamic range (WDR) spinal trigeminal nucleus caudalis (SpVc) neurons in response to nociceptive and non-nociceptive mechanical stimulation in vivo. Recordings of extracellular single units were obtained from SpVc neurons when orofacial mechanical stimulation was applied to anesthetized rats. The average firing rate of SpVc WDR neurons, to both non-noxious and noxious mechanical stimuli, was significantly and dose-dependently inhibited by MYR (1–5 mM, intravenously), and the maximum reversible inhibition of the discharge frequency, for both non-noxious and noxious mechanical stimuli, occurred within 5–10 min. The suppressive effects of MYR continued for about 20 min. These findings indicate that an acute, intravenous administration of MYR reduces the SpVc nociceptive transmission, likely through the inhibition of the CaV channels and by activating the Kv channels. Therefore, MYR might be utilized as a treatment for trigeminal nociceptive pain, without causing side effects. Full article

Neural progenitor cells (NPCs) are often used to study the subcellular mechanisms underlying differentiation into neurons in vitro. Works published to date have focused on the pathways that distinguish undifferentiated NPCs from mature neurons, neglecting the earlier and intermediate stages of this process. Current evidence suggests that mitochondria interaction with the ER is fundamental to a wide range of intracellular processes. However, it is not clear whether and how the mitochondria–ER interactions differ between NPCs and their differentiated counterparts. Here we take advantage of the widely used NPC line LUHMES to provide hints on the mitochondrial dynamic trait changes that occur during the first stage of their maturation into dopaminergic-like neurons. We observed that the morphology of mitochondria, their interaction with the ER, and the expression of several mitochondria–ER contact site resident proteins change, which suggests the potential contribution of mitochondria dynamics to NPC differentiation. Further studies will be needed to explore in depth these changes, and their functional outcomes, which may be relevant to the scientific community focusing on embryonic neurogenesis and developmental neurotoxicity. Full article

The present study examines whether the systemic application of naringenin (NRG) reduces inflammation-induced hyperexcitability in the spinal trigeminal nucleus caudalis (SpVc) related to hyperalgesia, and compares its impact with that of diclofenac (DIC). To provoke inflammation, the whisker pads of rats were injected with complete Freund’s adjuvant, and subsequently, mechanical stimuli were administered to the orofacial region to determine the escape threshold. Compared to naïve rats, the inflamed rats showed a significantly lower mechanical threshold, and this reduced threshold returned to normal levels two days post-administration of NRG, DIC, and half-dose DIC plus half-dose NRG (1/2 DIC + 1/2 NRG). Using extracellular single-unit recordings, the activity of SpVc wide-dynamic range neurons was measured in response to mechanical stimulation of the orofacial area under anesthesia. The average firing rate of SpVc neurons when exposed to both non-painful and painful mechanical stimuli was significantly reduced in inflamed rats following NRG, DIC, and 1/2 DIC + 1/2 NRG administration. The heightened average spontaneous activity of SpVc neurons in rats with inflammation was significantly reduced following NRG, DIC, and 1/2 DIC + 1/2 NRG administration. The increased average receptive field size observed in inflamed rats reverted to normal levels after either NRG, DIC, or 1/2 DIC + 1/2 NRG treatment. These findings indicate that NRG administration can reduce inflammatory hyperalgesia linked to the heightened excitability of SpVc wide-dynamic range neurons. Full article

Although astaxanthin (AST) has demonstrated a modulatory effect on voltage-gated Ca²⁺ (Cav) channels and excitatory glutamate neuronal transmission in vitro, particularly on the excitability of nociceptive sensory neurons, its action in vivo remains to be determined. This research sought to determine if an acute intravenous administration of AST in rats reduces the excitability of wide-dynamic range (WDR) spinal trigeminal nucleus caudalis (SpVc) neurons in response to nociceptive and non-nociceptive mechanical stimulation in vivo. In anesthetized rats, extracellular single-unit recordings were carried out on SpVc neurons following mechanical stimulation of the orofacial area. The average firing rate of SpVc WDR neurons in response to both gentle and painful mechanical stimuli significantly and dose-dependently decreased after the application of AST (1–5 mM, i.v.), and maximum suppression of discharge frequency for both non-noxious and nociceptive mechanical stimuli occurred within 10 min. These suppressive effects persisted for about 20 min. These results suggest that acute intravenous AST administration suppresses the SpVc nociceptive transmission, possibly by inhibiting Cav channels and excitatory glutamate neuronal transmission, implicating AST as a potential therapeutic agent for the treatment of trigeminal nociceptive pain without side effects. Full article

A long-standing research goal is to develop computing technologies that mimic the brain’s capabilities by implementing computation in electronic systems directly inspired by its structure, function, and operational mechanisms, using low-power, spike-based neural networks. The Loihi neuromorphic processor provides a low-power, large-scale network of programmable silicon neurons for brain-inspired artificial intelligence applications. This paper exploits the Loihi processors and a theory-guided methodology to enable unsupervised learning of spike patterns. Our method ensures efficient and rapid selection of the network’s hyperparameters, enabling the neuromorphic processor to generate attractor states through real-time unsupervised learning. Precisely, we follow a fast design process in which we fine-tune network parameters using mean-field theory. Moreover, we measure the network’s learning ability regarding its error correction and pattern completion aptitude. Finally, we observe the dynamic energy consumption of the neuron cores for each millisecond of simulation equal to 23 $\mathsf{\mu }$J/time step during the learning and recall phase for four attractors composed of 512 excitatory neurons and 256 shared inhibitory neurons. This study showcases how large-scale, low-power digital neuromorphic processors can be quickly programmed to enable the autonomous generation of attractor states. These attractors are fundamental computational primitives that theoretical analysis and experimental evidence indicate as versatile and reusable components suitable for a wide range of cognitive tasks. Full article

Disposable sensors are inexpensive, user-friendly sensing tools designed for rapid single-point measurements of a target. Disposable sensors have become more and more essential as diagnostic tools due to the growing demand for quick, easy-to-access, and reliable information related to the target. Dopamine (DA), a prevalent catecholamine neurotransmitter in the human brain, is associated with central nervous system activities and directly promotes neuronal communication. For the sensitive and selective estimation of DA, an enzyme-free amperometric sensor based on polyaniline-doped multi-walled carbon nanotubes (PANI-MWCNTs) drop-coated disposable screen-printed carbon electrodes (SPCEs) was fabricated. This PANI-MWCNTs-2/SPCE sensor boasts exceptional accuracy and sensitivity when working directly with ex vivo mouse brain homogenates. The sensor exhibited a detection limit of 0.05 μM (S/N = 3), and a wide linear range from 1.0 to 200 μM. The sensor’s high selectivity to DA amidst other endogenous interferents was recognized. Since the constructed sensor is enzyme-free yet biocompatible, it exhibited high stability in DA detection using ex vivo mouse brain homogenates extracted from both Parkinson’s disease and control mice models. This research thus presents new insights into understanding DA release dynamics at the tissue level in both of these models. Full article

The brain consists of an interconnected network of neurons tightly packed in the extracellular matrix (ECM) to form complex and heterogeneous composite tissue. According to recent biomimicry approaches that consider biological features as active components of biomaterials, designing a highly reproducible microenvironment for brain cells can represent a key tool for tissue repair and regeneration. Indeed, this is crucial to support cell growth, mitigate inflammation phenomena and provide adequate structural properties needed to support the damaged tissue, corroborating the activity of the vascular network and ultimately the functionality of neurons. In this context, electro-fluid dynamic techniques (EFDTs), i.e., electrospinning, electrospraying and related techniques, offer the opportunity to engineer a wide variety of composite substrates by integrating fibers, particles, and hydrogels at different scales—from several hundred microns down to tens of nanometers—for the generation of countless patterns of physical and biochemical cues suitable for influencing the in vitro response of coexistent brain cell populations mediated by the surrounding microenvironment. In this review, an overview of the different technological approaches—based on EFDTs—for engineering fibrous and/or particle-loaded composite substrates will be proposed. The second section of this review will primarily focus on describing current and future approaches to the use of composites for brain applications, ranging from therapeutic to diagnostic/theranostic use and from repair to regeneration, with the ultimate goal of providing insightful information to guide future research efforts toward the development of more efficient and reliable solutions. Full article

This study aimed at analyzing the corneal neural regeneration in ankylosing spondylitis patients using in vivo corneal confocal microscopy in correlation with Langerhans cell density, morphology, and dry eye parameters. Approximately 24 ankylosing spondylitis subjects and 35 age- and gender-matched control subjects were enrolled. Data analysis showed that all corneal nerve-fiber descriptives were lower in the ankylosing spondylitis group, implicating disrupted neural regeneration. Peripheral Langerhans cell density showed a negative correlation with nerve fiber descriptions. A negative correlation between tear film break-up time and corneal nerve fiber total branch density was detected. The potential role of somatosensory terminal Piezo2 channelopathy in the pathogenesis of dry eye disease and ankylosing spondylitis is highlighted in our study, exposing the neuroimmunological link between these diseases. We hypothesized earlier that spinal neuroimmune-induced sensitization due to this somatosensory terminal primary damage could lead to Langerhans cell activation in the cornea, in association with downregulated Piezo1 channels on these cells. This activation could lead to a Th17/Treg imbalance in dry eye secondary to ankylosing spondylitis. Hence, the corneal Piezo2 channelopathy-induced impaired Piezo2-Piezo1 crosstalk could explain the disrupted neural regeneration. Moreover, the translation of our findings highlights the link between Piezo2 channelopathy-induced gateway to pathophysiology and the gateway reflex, not to mention the potential role of spinal wide dynamic range neurons in the evolution of neuropathic pain and the flare-ups in ankylosing spondylitis and dry eye disease. Full article

Retinal neurons that form ribbon-style synapses operate over a wide dynamic range, continuously relaying visual information to their downstream targets. The remarkable signaling abilities of these neurons are supported by specialized presynaptic machinery, one component of which is syntaxin3B. Syntaxin3B is an essential t-SNARE protein of photoreceptors and bipolar cells that is required for neurotransmitter release. It has a light-regulated phosphorylation site in its N-terminal domain at T14 that has been proposed to modulate membrane fusion. However, a direct test of the latter has been lacking. Using a well-controlled in vitro fusion assay, we found that a phosphomimetic T14 syntaxin3B mutation leads to a small but significant enhancement of SNARE-mediated membrane fusion following the formation of the t-SNARE complex. While the addition of Munc18a had only a minimal effect on membrane fusion mediated by SNARE complexes containing wild-type syntaxin3B, a more significant enhancement was observed in the presence of Munc18a when the SNARE complexes contained a syntaxin3B T14 phosphomimetic mutant. Finally, we showed that the retinal-specific complexins (Cpx III and Cpx IV) inhibited membrane fusion mediated by syntaxin3B-containing SNARE complexes in a dose-dependent manner. Collectively, our results establish that membrane fusion mediated by syntaxin3B-containing SNARE complexes is regulated by the T14 residue of syntaxin3B, Munc18a, and Cpxs III and IV. Full article

Healthy brains display a wide range of firing patterns, from synchronized oscillations during slow-wave sleep to desynchronized firing during movement. These physiological activities coexist with periods of pathological hyperactivity in the epileptic brain, where neurons can fire in synchronized bursts. Most cortical neurons are pyramidal regular spiking (RS) cells with frequency adaptation and do not exhibit bursts in current-clamp experiments (in vitro). In this work, we investigate the transition mechanism of spike-to-burst patterns due to slow potassium and calcium currents, considering a conductance-based model of a cortical RS cell. The joint influence of potassium and calcium ion channels on high synchronous patterns is investigated for different synaptic couplings ($g_{\mathrm{syn}}$) and external current inputs (I). Our results suggest that slow potassium currents play an important role in the emergence of high-synchronous activities, as well as in the spike-to-burst firing pattern transitions. This transition is related to the bistable dynamics of the neuronal network, where physiological asynchronous states coexist with pathological burst synchronization. The hysteresis curve of the coefficient of variation of the inter-spike interval demonstrates that a burst can be initiated by firing states with neuronal synchronization. Furthermore, we notice that high-threshold ($I_{\mathrm{L}}$) and low-threshold ($I_{\mathrm{T}}$) ion channels play a role in increasing and decreasing the parameter conditions ($g_{\mathrm{syn}}$ and I) in which bistable dynamics occur, respectively. For high values of $I_{\mathrm{L}}$ conductance, a synchronous burst appears when neurons are weakly coupled and receive more external input. On the other hand, when the conductance $I_{\mathrm{T}}$ increases, higher coupling and lower I are necessary to produce burst synchronization. In light of our results, we suggest that channel subtype-specific pharmacological interactions can be useful to induce transitions from pathological high bursting states to healthy states. Full article

Autistic spectrum disease (ASD) is an increasingly common diagnosis nowadays with a prevalence of 1–2% in most countries. Its complex causality—a combination of genetic, immune, metabolic, and environmental factors—is translated into pleiomorphic developmental disorders of various severity, which have two main aspects in common: repetitive, restrictive behaviors and difficulties in social interaction varying from awkward habits and verbalization to a complete lack of interest for the outside world. The wide variety of ASD causes also makes it very difficult to find a common denominator—a disease biomarker and medication—and currently, there is no commonly used diagnostic and therapeutic strategy besides clinical evaluation and psychotherapy. In the CORDUS clinical study, we have administered autologous cord blood to ASD kids who had little or no improvement after other treatments and searched for a biomarker which could help predict the degree of improvement in each patient. We have found that the neuron-specific enolase (NSE) was elevated above the normal clinical range (less than 16.3 ng/mL) in the vast majority of ASD kids tested in our study (40 of 41, or 97.5%). This finding opens up a new direction for diagnostic confirmation, dynamic evaluation, and therapeutic intervention for ASD kids. Full article