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Circadian desynchrony induced by shiftwork or jet lag is detrimental to metabolic health, but how synchronous or desynchronous signals are transmitted among tissues is unknown. We report that liver molecular clock dysfunction is signaled to the brain through the hepatic vagal afferent nerve (HVAN), leading to altered food intake patterns that are corrected by ablation of the HVAN. Hepatic branch vagotomy also prevents food intake disruptions induced by high-fat diet feeding and reduces body weight gain. Our findings reveal a homeostatic feedback signal that relies on communication between the liver and the brain to control circadian food intake patterns. This identifies the hepatic vagus nerve as a potential therapeutic target for obesity in the setting of chronodisruption. [ABSTRACT FROM AUTHOR]

The CA1 region of the hippocampus is one of the most studied regions of the rodent brain, thought to play an important role in cognitive functions such as memory and spatial navigation. Despite a wealth of experimental data on its structure and function, it has been challenging to integrate information obtained from diverse experimental approaches. To address this challenge, we present a community-based, full-scale in silico model of the rat CA1 that integrates a broad range of experimental data, from synapse to network, including the reconstruction of its principal afferents, the Schaffer collaterals, and a model of the effects that acetylcholine has on the system. We tested and validated each model component and the final network model, and made input data, assumptions, and strategies explicit and transparent. The unique flexibility of the model allows scientists to potentially address a range of scientific questions. In this article, we describe the methods used to set up simulations to reproduce in vitro and in vivo experiments. Among several applications in the article, we focus on theta rhythm, a prominent hippocampal oscillation associated with various behavioral correlates and use our computer model to reproduce experimental findings. Finally, we make data, code, and model available through the hippocampushub.eu portal, which also provides an extensive set of analyses of the model and a user-friendly interface to facilitate adoption and usage. This community-based model represents a valuable tool for integrating diverse experimental data and provides a foundation for further research into the complex workings of the hippocampal CA1 region. Integrating data from different experimental approaches into one model is challenging. This study presents a community-based, full-scale in silico model of the rat hippocampal CA1 region that integrates diverse experimental data from synapse to network. [ABSTRACT FROM AUTHOR]

Chronic pelvic pain (CPP) is the most debilitating symptom of gynaecological disorders such as endometriosis. However, it remains unclear how sensory neurons from pelvic organs affected by endometriosis, such as the female reproductive tract, detect and transmit nociceptive events and how these signals are processed within the central nervous system (CNS). Using a previously characterized mouse model of endometriosis, we investigated whether the increased pain sensitivity occurring in endometriosis could be attributed to (i) changes in mechanosensory properties of sensory afferents innervating the reproductive tract, (ii) alterations in sensory input from reproductive organs to the spinal cord or (iii) neuroinflammation and sensitization of spinal neural circuits. Mechanosensitivity of vagina‐innervating primary afferents was examined using an ex vivo single‐unit extracellular recording preparation. Nociceptive signalling from the vagina to the spinal cord was quantified by phosphorylated MAP kinase ERK1/2 immunoreactivity. Immunohistochemistry was used to determine glial and neuronal circuit alterations within the spinal cord. We found that sensory afferents innervating the rostral, but not caudal portions of the mouse vagina, developed mechanical hypersensitivity in endometriosis. Nociceptive signalling from the vagina to the spinal cord was significantly enhanced in mice with endometriosis. Moreover, mice with endometriosis developed microgliosis, astrogliosis and enhanced substance P neurokinin‐1 receptor immunoreactivity within the spinal cord, suggesting the development of neuroinflammation and sensitization of spinal circuitry in endometriosis. These results demonstrate endometriosis‐induced neuroplasticity occurring at both peripheral and central sites of sensory afferent pathways. These findings may help to explain the altered sensitivity to pain in endometriosis and provide a novel platform for targeted pain relief treatments for this debilitating disorder. [ABSTRACT FROM AUTHOR]

The current incidence of chronic kidney disease‐associated pruritus (CKD‐aP) in patients with end‐stage renal disease (ESRD) is approximately 70%, especially in those receiving dialysis, which negatively affects their work and private lives. The CKD‐aP pathogenesis remains unclear, but uremic toxin accumulation, histamine release, and opioid imbalance have been suggested to lead to CKD‐aP. Current therapeutic approaches, such as opioid receptor modulators, antihistamines, and ultraviolet B irradiation, are associated with some limitations and adverse effects. The skin barrier is the first defense in preventing external injury to the body. Patients with chronic kidney disease often experience itch due to the damaged skin barrier and reduced secretion of sweat and secretion from sebaceous glands. Surprisingly, skin barrier‐repairing agents repair the skin barrier and inhibit the release of inflammatory cytokines, maintain skin immunity, and ameliorate the micro‐inflammatory status of afferent nerve fibers. Here, we summarize the epidemiology, pathogenesis, and treatment status of CKD‐aP and explore the possibility of skin barrier repair in CKD‐aP treatment. [ABSTRACT FROM AUTHOR]

Endogenous shifts of spatial attention toward an upcoming stimulus are associated with improvements in behavioral responses to the stimulus, preparatory retinotopic shifts in alpha power, and changes in ERPs. Although attentional modulation of several early sensory ERPs is well established, there is still debate about under what circumstances attention affects the earliest cortical visual evoked response—the C1 ERP component—which is putatively generated from afferent input into primary visual cortex. Moreover, the effects of spatial attention on the recently discovered ERP signature of evidence accumulation—the central parietal positivity (CPP)—have not been fully characterized. The present study assessed the effect of spatial attention on the C1 and CPP components through a spatially cued contrast discrimination task using stimuli that were specifically designed to produce large-amplitude C1 responses and that varied in sensory evidence strength to characterize the CPP. Participants responded according to which of two checkerboard stimuli had greater contrast following an 80% valid cue toward the upper or lower visual field. Prestimulus alpha power changed topographically based on the cue, suggesting participants shifted attention to prepare for the upcoming stimuli. Despite these attentional shifts in alpha power and the fact that the stimuli reliably elicited C1 responses several times greater than many prior studies, there was no evidence of an attention effect on the C1. The CPP, however, showed a clear increase in build-up rate on valid trials. Our findings suggest that endogenous attention may not affect the early C1 ERP component but may improve behavior at a decision stage, as reflected in brain signals related to evidence accumulation (the CPP). [ABSTRACT FROM AUTHOR]

Purpose: The aim of this cadaveric study was to further describe the vascular supply of the radial, posterior interosseous and superficial radial nerves. Methods: 11 cadaveric upper limbs, injected with colored latex, were dissected. Vascular afferents to the radial nerve, superficial radial nerve (SRN) and posterior interosseous nerve (PIN) were described and located. Their origin was identified and its distance to interepicondylar line was measured. Results: The radial nerve had an average of 3 vascular afferents (1–5), of septomuscular origin in 54% of cases. 46% came from adjacent arteries. The PIN had an average of 8 vascular afferents (6–14), arising from septomuscular branches in 82% of cases. The PIN was vascularized in 100% of cases by a large arterial plexus originating from the supinator muscle between its two heads. The SRN had an average of 4 vascular afferents (3–7). Before crossing the septum of the brachioradialis, vascularization was predominantly septomuscular; after crossing the septum, the nerve was exclusively vascularized by septocutaneous arteries. Conclusion: This is the first study to describe the vascularization of the radial nerve and its terminal branches along their entire length. Our results are in line with the data available in the literature. An arterial plexus between the two heads of the supinator was surrounding the PIN in all cases. This vascular plexus might be involved in dynamic compression of the posterior interosseous nerve. [ABSTRACT FROM AUTHOR]

The article titled "A Hundred Faces for a Unique Disorder: Hereditary Spastic Paraplegia" provides an overview of Hereditary Spastic Paraplegia (HSP), a group of inherited neurodegenerative disorders characterized by lesions of the pyramidal tract. The disorder presents with progressive lower limb spasticity and weakness, and exhibits wide clinical and genetic variability. The article discusses the genetic causes of HSP, including various inheritance patterns and the involvement of over 80 genes. It also describes the clinical presentation of HSP, highlighting the differences based on age of onset and the presence of additional neurological or non-neurological features. This document provides information on hereditary spastic paraplegia (HSP), a rare and diverse clinical disorder characterized by progressive weakness and spasticity in the lower limbs. The diagnosis of HSP is based on symptoms, family history, and genetic analysis. Treatment aims to manage symptoms and prevent complications, but there is currently no cure for HSP. The prognosis varies, with some individuals experiencing severe disability and others having a normal life expectancy. Early diagnosis and treatment can help reduce symptoms associated with HSP. [Extracted from the article]

Numerous studies have underscored the close relationship between the auditory and vibrotactile modality. For instance, in the peripheral structures of both modalities, afferent nerve fibers synchronize their activity to the external sensory stimulus, thereby providing a temporal code linked to pitch processing. The Frequency Following Response is a neurological measure that captures this phase locking activity in response to auditory stimuli. In our study, we investigated whether this neural signal is influenced by the simultaneous presentation of a vibrotactile stimulus. Accordingly, our findings revealed a significant increase in phase locking to the fundamental frequency of a speech stimulus, while no such effects were observed at harmonic frequencies. Since phase locking to the fundamental frequency has been associated with pitch perceptual capabilities, our results suggests that audio-tactile stimulation might improve pitch perception in human subjects. [ABSTRACT FROM AUTHOR]

Memory consolidation involves repeated replay of new information by the hippocampus, which transfers memories to the neocortex for long-term storage. This occurs mainly during slow wave sleep, a phase characterized in the cortex by low cholinergic tone and low afferent input. High cholinergic tone has been shown to hamper memory consolidation, probably mediated by reduced network excitability (the ease of activity propagation in a network). We used cortical neuronal networks on multi electrode arrays to investigate whether low background input contributes to memory consolidation. Networks received focal electrical stimuli to memorize, with or without background afferent input (global optogenetic stimulation). Background stimulation hampered memory formation and consolidation, confirming the importance of low background input. Moreover, it lowered network excitability, similar to high cholinergic tone. These findings suggest that high network excitability is a critical feature of slow wave sleep that facilitates memory consolidation. [ABSTRACT FROM AUTHOR]

This study investigated the influence of stimulation parameters on torque production when combining a brief muscle lengthening with electrical stimulation. Fifteen volunteers participated in one experimental session where two distinct stimulation modalities were compared: wide-pulse high-frequency (WPHF; pulse duration: 1 ms, frequency: 100 Hz), favoring afferent pathway activation, and narrow-pulse low-frequency (NPLF; pulse duration: 0.05 ms, frequency: 20 Hz), favoring activation of the efferent pathway. Both stimulation modalities were applied to evoke 5–10% of maximal voluntary contraction either in isometric conditions (WPHF and NPLF) or in combination with a muscle lengthening (lengthening condition: WPHF + LEN and NPLF + LEN). The torque-time integral (TTI) during the stimulation trains and the muscle activity after the cessation of the stimulation trains [sustained electromyographic (EMG) activity, normalized to the maximal EMG activity] were assessed and compared between the stimulation modalities and the conditions (2-way ANOVA). An interaction effect was obtained, revealing significant differences in TTI and sustained EMG activity between WPHF + LEN and the other tested conditions (P = 0.048 and P = 0.044, respectively). TTI and sustained EMG activity were higher for WPHF + LEN (228.4 ± 105.3 Nm·s and 0.085 ± 0.070, respectively) compared to WPHF (168.4 ± 72.9 Nm·s; 0.052 ± 0.026), NPLF + LEN (136.4 ± 38.9 Nm·s; 0.031 ± 0.016), and NPLF (125.2 ± 36.1 Nm·s; 0.028 ± 0.015). The increased TTI during the WPHF + LEN condition suggests that the contribution of afferent pathways to the evoked torque can be enhanced with the muscle lengthening superimposition. They highlight the importance of using WPHF stimulation that already solicits Ia afferents, to benefit from the cumulative afferent activation induced by the muscle lengthening to further increase torque production. NEW & NOTEWORTHY: The results of the present study highlight the importance of using electrical stimulation modalities that preferentially activate Ia afferents to take advantage of the superimposition of muscle lengthening to further enhance afferent pathways' contribution to evoked torque and, in turn, increase torque production. These results offer the opportunity to improve the efficacy of the wide-pulse high-frequency stimulation modality. [ABSTRACT FROM AUTHOR]

Summary: Sleep is a brain state characterised by a low vigilance level and diminished consciousness. Reaction to and processing of external stimuli is attenuated in sleep. During sleep, the reticular thalamic nucleus reduces the flow of sensory activity to the cerebral cortex through inhibition of the thalamus. This sensory gating process facilitates sleep. After reaching the afferent layers of primary cortex, the reduced sensory flow is adjusted, gained, and processed within various cortical layers before being transferred by the corticofugal system back to appropriate subdivisions of the thalamus as feedback. Thalamic subdivisions then dispatch this sensory information to related areas of the cerebral cortex, where it is (sub)consciously perceived. When necessary, a sleeping individual can be awakened by a wake‐up call, either by stimuli indicating danger, or by personally meaningful stimuli. It is safe for a sleeping individual that it can be aroused when necessary. Evidently, there are two processes by which the brain adjusts the response to sensory stimuli before entering (sub)consciousness. Firstly 'sensory gating', a process favourable to the maintenance of sleep by reducing the sensory input to the brain through the reticular thalamic nucleus and secondly 'sensory gaining', a process implying that the gained preserved sensory input is continuously analysed by the corticofugal system to detect dangerous and relevant environmental elements, indispensable for safeness and well‐being of the sleeper. [ABSTRACT FROM AUTHOR]

Gastrointestinal vagal afferents play an important role in communicating food related information from the gut to the brain. This information initiates vago‐vagal reflexes essential for gut functions, including gut motility and secretions. These afferents also play a role in energy homeostasis, signalling the arrival, amount and nutrient composition of a meal to the central nervous system where it is processed ultimately leading to termination of a meal. Vagal afferent responses to food related stimuli demonstrate a high degree of plasticity, responding to short term changes in nutritional demand, such as the fluctuations that occur across a 24‐hr or in response to a fast, as well as long term changes in energy demand, such as occurs during pregnancy. This plasticity is disrupted in disease states, such as obesity or chronic stress where there is hypo‐ and hypersensitivity of these afferents, respectively. Improved understanding of the plasticity of these afferents will enable identification of new treatment options for diseases associated with vagal afferent function. [ABSTRACT FROM AUTHOR]

Background and Aim: Endoscopic ultrasound‐guided gastroenterostomy is a procedure used to connect the stomach and dilated afferent loop using a stent under endoscopic ultrasound for afferent loop syndrome. However, the actual efficacy and safety of this procedure remain unclear. Therefore, this retrospective study aimed to evaluate the efficacy and safety of endoscopic ultrasound‐guided gastroenterostomy using a laser‐cut‐type fully covered self‐expandable metallic stent and an anchoring plastic stent for afferent loop syndrome. Methods: Technical and clinical success rates, adverse events, recurrent intestinal obstruction rates, time to recurrent intestinal obstruction, and technical and clinical success rates of re‐intervention were evaluated in intended patients who underwent endoscopic ultrasound‐guided gastroenterostomy for afferent loop syndrome from October 2018 to August 2022. Results: In 25 intended patients with afferent loop syndrome who intended endoscopic ultrasound‐guided gastroenterostomy, the technical success rate was 100% (25/25), whereas the clinical success rate was 96% (24/25). Two patients experienced grade ≥ 3 early adverse events, including one with intra‐abdominal abscess and one with hypotension. Both events were attributed to intestinal fluid leakage. No late adverse events were observed. The recurrent intestinal obstruction rate was 32% (8/25), and the median time to recurrent intestinal obstruction was 6.5 months (95% confidence interval: 2.8–not available). The technical and clinical success rates of re‐intervention were both 100% (8/8). Conclusions: Endoscopic ultrasound‐guided gastroenterostomy using a fully covered self‐expandable metallic stent and an anchoring plastic stent is effective and safe as a treatment procedure for afferent loop syndrome. [ABSTRACT FROM AUTHOR]

Acetylcholine esterases (AChEs) are essential enzymes in cholinergic synapses, terminating neurotransmission by hydrolysing acetylcholine. While membrane bound AChEs at synaptic clefts efficiently perform this task, soluble AChEs are less stable and effective, but function over broader areas. In vertebrates, a single gene produces alternatively spliced forms of AChE, whereas invertebrates often have multiple genes, producing both enzyme types. Despite their significance as pesticide targets, the physiological roles of invertebrate AChEs remain unclear. Here, we characterized seven putative AChEs in the wandering spider, Cupiennius salei, a model species for neurophysiological studies. Sequence analyses and homology modeling predicted CsAChE7 as the sole stable, membrane‐bound enzyme functioning at synaptic clefts, while the others are likely soluble enzymes. In situ hybridization of sections from the spider's nervous system revealed CsAChE7 transcripts co‐localizing with choline acetyltransferase in cells that also exhibited AChE activity. CsAChE7 transcripts were also found in rapidly adapting mechanosensory neurons, suggesting a role in precise and transient activation of postsynaptic cells, contrasting with slowly adapting, also cholinergic, neurons expressing only soluble AChEs, which allow prolonged activation of postsynaptic cells. These findings suggest that cholinergic transmission is influenced not only by postsynaptic receptors but also by the enzymatic properties regulating acetylcholine clearance. We also show that acetylcholine is a crucial neurotransmitter in the spider's visual system and sensory and motor pathways, but absent in excitatory motor neurons at neuromuscular junctions, consistent with other arthropods. Our findings on sequence structures may have implications for the development of neurological drugs and pesticides. [ABSTRACT FROM AUTHOR]

Local vibration (LV) mainly stimulates primary afferents (Ia) and can induce a tonic vibration reflex (TVR) and an illusion of movement. This study aimed to evaluate the effect of these two phenomena on maximal voluntary isometric contraction (MVIC) capacity. LV (80 Hz) was applied to the wrist flexor muscles in two randomized experiments for 6 min. LV conditions were adjusted to promote either TVR (visual focus on the vibrated wrist) or ILLUSION [hand hidden, visual focus on electromyographic activity of the flexor carpi radialis muscle (FCR)]. Mechanical and electromyographic (EMG) responses of the FCR and extensor carpi radialis muscles were recorded during MVIC in flexion and extension and during electrically evoked contractions at supramaximal intensity. Measurements were performed before (10 min and just before) and after (0 and 30 min) LV protocol. An increase in FCR EMG was observed during LV in the TVR condition (+340%) compared with the illusion condition (P = 0.003). In contrast, the movement illusion was greater in the ILLUSION condition (assessed through subjective scales) (P = 0.004). MVIC was reduced in flexion only after the TVR condition (≈ − 7 % , all P < 0.034). Moreover, the decrease in force was correlated with the amount of TVR recorded on the FCR muscle (r = −0.64, P = 0.005). Although potentiated doublets of each muscle did not evolve differently between conditions, a decrease was observed between the first and the last measure. In conclusion, when conducting research to assess maximal strength, it is necessary to have better control and reporting of the phenomena induced during LV. NEW & NOTEWORTHY: The maximal force production of the vibrated muscle is reduced after 6 min of LV only in TVR condition. Furthermore, the amount of TVR is negatively correlated with this force decrease. When measuring the effects of LV on maximal force production, it is important to control and report any phenomena induced during vibration, such as TVR or movement illusion, which can be achieved by recording EMG activity of vibrated muscle and quantifying illusion. [ABSTRACT FROM AUTHOR]

The absence of a comprehensive understanding of the neural basis of spontaneous pain limits the development of therapeutic strategies targeting this primary complaint of patients with chronic pain. Here we report a distinct neuronal ensemble within the prelimbic cortex which processes signals related to spontaneous pain in rats with chronic inflammatory pain. This neuronal ensemble specifically encodes spontaneous pain-related behaviors, independently of other locomotive and evoked behaviors. Activation of this neuronal ensemble elicits marked spontaneous pain-like behaviors and enhances nociceptive responses, whereas prolonged silencing of its activities alleviates spontaneous pain and promotes overall recovery from inflammatory pain. Notably, afferents from the primary somatosensory cortex and infralimbic cortex bidirectionally modulate the activities of the spontaneous pain-responsive prelimbic cortex neuronal ensemble and pain behaviors. These findings reveal the cortical basis of spontaneous pain at the neuronal level, highlighting a distinct neuronal ensemble within the prelimbic cortex and its associated pain-regulatory brain networks. Neural mechanisms underlying spontaneous pain are not fully understood. Here authors identify a unique neuronal ensemble in the PL of rats with chronic inflammation, encoding spontaneous pain independently. Activating this ensemble triggers pain-like behaviors, while inhibiting it alleviates pain and accelerates recovery. [ABSTRACT FROM AUTHOR]

In this work, we couple a lumped‐parameter closed‐loop model of the cardiovascular system with a physiologically‐detailed mathematical description of the baroreflex afferent pathway. The model features a classical Hodgkin–Huxley current‐type model for the baroreflex afferent limb (primary neuron) and for the second‐order neuron in the central nervous system. The pulsatile arterial wall distension triggers a frequency‐modulated sequence of action potentials at the afferent neuron. This signal is then integrated at the brainstem neuron model. The efferent limb, representing the sympathetic and parasympathetic nervous system, is described as a transfer function acting on heart and blood vessel model parameters in order to control arterial pressure. Three in silico experiments are shown here: a step increase in the aortic pressure to evaluate the functionality of the reflex arch, a hemorrhagic episode and an infusion simulation. Through this model, it is possible to study the biophysical dynamics of the ionic currents proposed for the afferent limb components of the baroreflex during the cardiac cycle, and the way in which currents dynamics affect the cardiovascular function. Moreover, this system can be further developed to study in detail each baroreflex loop component, helping to unveil the mechanisms involved in the cardiovascular afferent information processing. [ABSTRACT FROM AUTHOR]

The nucleus of the solitary tract (NTS) receives direct viscerosensory vagal afferent input that drives autonomic reflexes, neuroendocrine function and modulates behaviour. A subpopulation of NTS neurons project to the nucleus accumbens (NAc); however, the function of this NTS‐NAc pathway remains unknown. A combination of neuroanatomical tracing, slice electrophysiology and fibre photometry was used in mice and/or rats to determine how NTS‐NAc neurons fit within the viscerosensory network. NTS‐NAc projection neurons are predominantly located in the medial and caudal portions of the NTS with 54 ± 7% (mice) and 65 ± 3% (rat) being TH‐positive, representing the A2 NTS cell group. In horizontal brainstem slices, solitary tract (ST) stimulation evoked excitatory post‐synaptic currents (EPSCs) in NTS‐NAc projection neurons. The majority (75%) received low‐jitter, zero‐failure EPSCs characteristic of monosynaptic ST afferent input that identifies them as second order to primary sensory neurons. We then examined whether NTS‐NAc neurons respond to cholecystokinin (CCK, 20 μg/kg ip) in vivo in both mice and rats. Surprisingly, there was no difference in the number of activated NTS‐NAc cells between CCK and saline‐treated mice. In rats, just 6% of NTS‐NAc cells were recruited by CCK. As NTS TH neurons are the primary source for NAc noradrenaline, we measured noradrenaline release in the NAc and showed that NAc noradrenaline levels declined in response to cue‐induced reward retrieval but not foot shock. Combined, these findings suggest that high‐fidelity afferent information from viscerosensory afferents reaches the NAc. These signals are likely unrelated to CCK‐sensitive vagal afferents but could interact with other sensory and higher order inputs to modulate learned appetitive behaviours. [ABSTRACT FROM AUTHOR]

Research has shown that talkers reliably coordinate the timing of articulator movements across variation in production rate and syllable stress, and that this precision of inter-articulator timing instantiates phonetic structure in the resulting acoustic signal. We here tested the hypothesis that immediate auditory feedback helps regulate that consistent articulatory timing control. Talkers with normal hearing recorded 480 /tV#Cat/ utterances using electromagnetic articulography, with alternative V (/ɑ/-/ɛ/) and C (/t/-/d/), across variation in production rate (fast-normal) and stress (first syllable stressed-unstressed). Utterances were split between two listening conditions: unmasked and masked. To quantify the effect of immediate auditory feedback on the coordination between the jaw and tongue-tip, the timing of tongue-tip raising onset for C, relative to the jaw opening-closing cycle for V, was obtained in each listening condition. Across both listening conditions, any manipulation that shortened the jaw opening-closing cycle reduced the latency of tongue-tip movement onset, relative to the onset of jaw opening. Moreover, tongue-tip latencies were strongly affiliated with utterance type. During auditory masking, however, tongue-tip latencies were less strongly affiliated with utterance type, demonstrating that talkers use afferent auditory signals in real-time to regulate the precision of inter-articulator timing in service to phonetic structure. [ABSTRACT FROM AUTHOR]

The effectiveness of activated Ia afferents to discharge α-motoneurons is decreased during passive muscle lengthening compared with static and shortening muscle conditions. Evidence suggests that these regulations are explained by 1) greater postactivation depression induced by homosynaptic postactivation depression (HPAD) and 2) primary afferent depolarization (PAD). It remains uncertain whether muscle length impacts the muscle lengthening-related aspect of regulation of the effectiveness of activated Ia afferents to discharge α-motoneurons, HPAD, PAD, and heteronymous Ia facilitation (HF). We conducted a study involving 15 healthy young individuals. We recorded conditioned or nonconditioned soleus Hoffmann (H) reflex with electromyography (EMG) to estimate the effectiveness of activated Ia afferents to discharge α-motoneurons, HPAD, PAD, and HF during passive shortening, static, and lengthening muscle conditions at short, intermediate, and long lengths. Our results show that the decrease of effectiveness of activated Ia afferents to discharge α-motoneurons and increase of postactivation depression during passive muscle lengthening occur at all muscle lengths. For PAD and HF, we found that longer muscle length increases the magnitude of regulation related to muscle lengthening. To conclude, our findings support an inhibitory effect (resulting from increased postactivation depression) of muscle lengthening and longer muscle length on the effectiveness of activated Ia afferents to discharge α-motoneurons. The increase in postactivation depression associated with muscle lengthening can be attributed to the amplification of Ia afferents discharge. NEW & NOTEWORTHY: Original results are that in response to passive muscle lengthening and increased muscle length, inhibition of the effectiveness of activated Ia afferents to discharge α-motoneurons increases, with primary afferent depolarization and homosynaptic postactivation depression mechanisms playing central roles in this regulatory process. Our findings highlight for the first time a cumulative inhibitory effect of muscle lengthening and increased muscle length on the effectiveness of activated Ia afferents to discharge α-motoneurons. [ABSTRACT FROM AUTHOR]

Weak sensory noise acts on the nervous system and promotes sensory and motor functions. This phenomenon is called stochastic resonance and is expected to be applied for improving biological functions. This study investigated the effect of electrical stimulation on grip force adjustment ability. The coefficient of variation and absolute motor error in grip force was measured during a visuomotor tracking task under different intensities of somatosensory noise. Depending on the style of force exertion, the grip movement used in the visuomotor tracking task consisted of force generation (FG), force relaxation (FR), and constant contraction (Constant) phases. The subthreshold condition resulted in significantly lower coefficient of variation in the Constant phase and motor errors in the FG and Constant phases than the no-noise condition. However, the differences among the other conditions were insignificant. Additionally, we examined the correlation between the motor error in the condition without electrical stimulation and the change in motor error induced by subthreshold electrical stimulation. Significant negative correlations were observed in all FG, FR, and Constant phases. These results indicated that somatosensory noise had a strong effect on subjects with large motor errors and enhanced the grip force adjustment ability. By contrast, subjects with small motor errors had weak improvement in motor control. Although the effect of subthreshold noise varies depending on the individual differences, stochastic resonance is effective in improving motor control ability. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate whether the dorsal claustrum receives afferent input from the intralaminar thalamic nuclei – centromedian nucleus, central lateral nucleus and paracentral nucleus. The intralaminar thalamic nuclei of eight cats were electrolytically lesioned. We obtained samples from the dorsal claustrum for electron microscopic analysis from the second to the seventh post-procedural day. Two types of degenerated synaptic boutons were observed: electron-dense which formed the majority of boutons, and electron-lucent comprising the remaining samples. Between the second and seventh post-procedural day, we observed a steady increase in the number of electron-dense boutons which were diffusely distributed throughout the dorsal claustrum. Electron-dense degenerated boutons formed asymmetrical contacts with dendritic spines as well as with small and medium-sized dendrites. In contrast, electron-lucent degenerated boutons were observed in earlier post-procedural periods and formed symmetrical axodendritic contacts. [ABSTRACT FROM AUTHOR]

Background and Purpose: Many medications taste intensely bitter. The innate aversion to bitterness affects medical compliance, especially in children. There is a clear need to develop bitter blockers to suppress the bitterness of vital medications. Bitter taste is mediated by TAS2R receptors. Because different pharmaceutical compounds activate distinct sets of TAS2Rs, targeting specific receptors may only suppress bitterness for certain, but not all, bitter‐tasting compounds. Alternative strategies are needed to identify universal bitter blockers that will improve the acceptance of every medication. Taste cells in the mouth transmit signals to afferent gustatory nerve fibres through the release of ATP, which activates the gustatory nerve‐expressed purine receptors P2X2/P2X3. We hypothesized that blocking gustatory nerve transmission with P2X2/P2X3 inhibitors (e.g. 5‐(5‐iodo‐4‐methoxy‐2‐propan‐2‐ylphenoxy)pyrimidine‐2,4‐diamine [AF‐353]) would reduce bitterness for all medications and bitter compounds. Experimental Approach: Human sensory taste testing and mouse behavioural analyses were performed to determine if oral application of AF‐353 blocks perception of bitter taste and other taste qualities but not non‐gustatory oral sensations (e.g. tingle). Key Results: Rinsing the mouth with AF‐353 in humans or oral swabbing it in mice suppressed the bitter taste and avoidance behaviours of all compounds tested. We further showed that AF‐353 suppressed other taste qualities (i.e. salt, sweet, sour and savoury) but had no effects on other oral or nasal sensations (e.g, astringency and oral tingle). Conclusion and Implications: This is the first time a universal, reversible taste blocker in humans has been reported. Topical application of P2X2/P2X3 inhibitor to suppress bitterness may improve medical compliance. [ABSTRACT FROM AUTHOR]

Background: Spinal manipulation (SMA) and spinal mobilization (SMO) are commonly utilized treatments for chronic low back pain (CLBP) Objective: To summarize the evidence describing the effects of SMA and SMO on trunk proprioception and the lumbar paravertebral muscle strength in patients with chronic low back pain (CLBP) Methods: A search was conducted in five databases and four sources of gray literature. The inclusion criteria were: individuals aged between 18 and 65 years with chronic low back pain (CLBP), of both sexes; no restrictions on publication period or language; studies employing spinal manipulation (SMA) or spinal mobilization (SMO) interventions; inclusion of a comparator group such as control, placebo, or other base therapies; and measurement of at least one of the following outcomes: paravertebral muscle strength, trunk proprioception, or postural control Results: Initially, 8187 references were identified through database searches. Among these, the review included seven randomized clinical trials, two non-randomized clinical trials, and two crossover clinical trials; no reviews were found meeting the inclusion criteria. After screening and selection, a total of 11 studies were included in the review, comprising 8 studies investigating spinal manipulation (SMA) and 3 studies investigating spinal mobilization (SMO). Conclusion: In patients with CLBP, SMA did not demonstrate a significant effect on proprioception but showed a notable effect on the maximum contraction of the lumbar multifidus muscle. Conversely, SMO exhibited beneficial effects on both proprioception and the generation of muscle strength in trunk extensors among patients with CLBP. Trial registration: Open Science Framework (OSF) osf.io/b5fym. [ABSTRACT FROM AUTHOR]

Background: The herbal Poria cocos -Liquorice drug pair (PLDP) possesses the ability to be a diuretic, stimulating the spleen and benefiting the kidney, which plays an important role in the treatment of Henoch–Schönlein purpura nephritis (HSPN). However, the mechanism of action is unknown. Objectives: Through the method of network pharmacology, this research sought to determine the mechanism of PLDP against HSPN. Materials and Methods: The screening of active ingredients in PLDP was conducted by Traditional Chinese Medicine Systems Pharmacology (TCMSP) databases, while their targets were obtained from the TCMSP and Swiss Target Prediction (STP) databases. The genes of HSPN were searched by OMIM, DisGeNET, and GeneCards databases. Then, the common targets of active ingredients in PLDP and HSPN were mapped by Venn analysis. To get the main targets, the researchers utilized the STRING database to construct the protein–protein interaction (PPI) network of the common targets. Then, the function of gene ontology (GO) and the enrichment of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of the main targets were examined on the Metascape database to identify the molecular mechanism of PLDP against HSPN. The most relevant signaling pathways with HSPN screened from the top 20 pathways were defined as the key pathways. Finally, the "active ingredient-main target-key pathway" network was built in order to identify the core targets and key active ingredients of PLDP against HSPN. Results: There were 101 active ingredients and 360 targets for PLDP. One hundred and fifty-seven genes for HSPN and 35 common targets between PLDP and HSPN were identified. Through the "active ingredient-main target-key pathway" network, quercetin, kaempferol, polyporenic acid C, dehydrotumulosic acid, poricoic acid A, and naringenin were identified as key active ingredients; TNF, NOS3, RELA, AKT1, ICAM1, and IFNG were identified as core targets; and the key pathways include TNF signaling pathways, HIF-1 signaling pathways, and IL-17 signaling pathways. Conclusion: The research initially investigated the pathways, active ingredients, and targets involved in PLDP against HSPN. The mechanism appears to be linked to its immunomodulatory and anti-inflammatory properties, thus establishing a scientific foundation for further investigation. [ABSTRACT FROM AUTHOR]

The 46th meeting of the Upper Midwest Neuro-Ophthalmology Group (UMNOG), held on July 26, 2024, and hosted by Northwestern University at Chicago, brought together a group of neuro-ophthalmologists, researchers, and trainees. This conference served as a forum for presenting research findings, illustrating challenging cases in clinical practice, and discussing them from an expert viewpoint. Key topics included visual outcomes following the treatment of various optic neuropathies, and advancements in diagnostic techniques, including the integration of machine learning. Case demonstrations covered a wide range of afferent and efferent neuro-ophthalmological conditions, primarily related to systemic illnesses and novel treatments. The proceedings aimed to disseminate valuable knowledge and foster further research, offering comprehensive insights into the discussion held during the meeting. [ABSTRACT FROM AUTHOR]

In the mammalian somatosensory system, polymodality is defined as the competence of some neurons to respond to multiple forms of energy (e.g., mechanical and thermal). This ability is thought to be an exclusive property of nociceptive neurons (polymodal C-fiber nociceptors) and one of the pillars of nociceptive peripheral plasticity. The current study uncovered a completely different neuronal sub-population with polymodal capabilities on the opposite mechanical modality spectrum (tactile). We have observed that several tactile afferents (1/5) can respond to cold in non-nociceptive ranges. These cells' mechanical thresholds and electrical properties are similar to any low-threshold mechano-receptors (LT), conducting in a broad range of velocities (Aδ to Aβ), lacking CGRP and TRPM8 receptors. Due to its density, cold-response range, speed, and response to injury (or lack thereof), we speculate on its role in controlling reflexive behaviors (wound liking and rubbing) and modulation of nociceptive spinal cord integration. Further studies are required to understand the mechanisms behind this neuron's polymodality, central architecture, and impact on pain perception. [ABSTRACT FROM AUTHOR]

Inhibitory circuits in the mammalian olfactory bulb (OB) dynamically reformat olfactory information as it propagates from peripheral receptors to downstream cortex. To gain mechanistic insight into how specific OB interneuron types support this sensory processing, we examine unitary synaptic interactions between excitatory mitral and tufted cells (MTCs), the OB projection neurons, and a conserved population of anaxonic external plexiform layer interneurons (EPL-INs) using pair and quartet whole-cell recordings in acute mouse brain slices. Physiological, morphological, neurochemical, and synaptic analyses divide EPL-INs into distinct subtypes and reveal that parvalbumin-expressing fast-spiking EPL-INs (FSIs) perisomatically innervate MTCs with release-competent dendrites and synaptically detonate to mediate fast, short-latency recurrent and lateral inhibition. Sparse MTC synchronization supralinearly increases this high-fidelity inhibition, while sensory afferent activation combined with single-cell silencing reveals that individual FSIs account for a substantial fraction of total network-driven MTC lateral inhibition. OB output is thus powerfully shaped by detonation-driven high-fidelity perisomatic inhibition. Inhibitory circuits in the mammalian olfactory bulb shape information as it propagates from peripheral receptors to the downstream cortex. This study reveals that fast-spiking interneurons perisomatically inhibit projection neurons in the mammalian olfactory bulb via synaptic detonation. [ABSTRACT FROM AUTHOR]

Louise Rosenblatt's well‐known concept of stance distinguishes between efferent reading (reading to take something away from the text) and aesthetic reading (reading for the experience of dwelling in the text). This article proposes a refinement to this binary, adding the concept of afferent reading. Afference, in biology, means a bringing‐to, and afferent reading includes what interpreters bring to a text. This article particularly considers how afference works in a world of transmedia iterations of a story. What do young readers bring to their interpretation of a version of a story from other versions of the same story or the same story world? How does the concept of afference improve the ability of teachers and other adult observers to consider different renditions of the same story as a potential asset to young interpreters rather than simply a form of repetition? [ABSTRACT FROM AUTHOR]

The emulation of tactile sensory nerves to achieve advanced sensory functions in robotics with artificial intelligence is of great interest. However, such devices remain bulky and lack reliable competence to functionalize further synaptic devices with proprioceptive feedback. Here, we report an artificial organic afferent nerve with low operating bias (−0.6 V) achieved by integrating a pressure-activated organic electrochemical synaptic transistor and artificial mechanoreceptors. The dendritic integration function for neurorobotics is achieved to perceive directional movement of object, further reducing the control complexity by exploiting the distributed and parallel networks. An intelligent robot assembled with artificial afferent nerve, coupled with a closed-loop feedback program is demonstrated to rapidly implement slip recognition and prevention actions upon occurrence of object slippage. The spatiotemporal features of tactile patterns are well differentiated with a high recognition accuracy after processing spike-encoded signals with deep learning model. This work represents a breakthrough in mimicking synaptic behaviors, which is essential for next-generation intelligent neurorobotics and low-power biomimetic electronics. Intelligent artificial tactile system for neurorobotics remains challenging. Here, Chen et al. developed an artificial organic afferent nerve to implement slip recognition and prevention actions by learning the real-time spatial information of directional touch. [ABSTRACT FROM AUTHOR]

Vagal afferents to the gastrointestinal tract are crucial for the regulation of food intake, signaling negative feedback that contributes to satiation and positive feedback that produces appetition and reward. Vagal afferents to the small intestinal mucosa contribute to this regulation by sensing luminal stimuli and reporting this information to the brain. These afferents respond to mechanical, chemical, thermal, pH, and osmolar stimuli, as well as to bacterial products and immunogens. Surprisingly, little is known about how these stimuli are transduced by vagal mucosal afferents or how their transduction is organized among these afferents' terminals. Furthermore, the effects of stimulus concentration ranges or physiological stimuli on vagal activity have not been examined for some of these stimuli. Also, detection of luminal stimuli has rarely been examined in rodents, which are most frequently used for studying small intestinal innervation. Here we review what is known about stimulus detection by vagal mucosal afferents and illustrate the complexity of this detection using nutrients as an exemplar. The accepted model proposes that nutrients bind to taste receptors on enteroendocrine cells (EECs), which excite them, causing the release of hormones that stimulate vagal mucosal afferents. However, evidence reviewed here suggests that although this model accounts for many aspects of vagal signaling about nutrients, it cannot account for all aspects. A major goal of this review is therefore to evaluate what is known about nutrient absorption and detection and, based on this evaluation, identify candidate mucosal cells and structures that could cooperate with EECs and vagal mucosal afferents in stimulus detection. [ABSTRACT FROM AUTHOR]

Although the introduction of drugs targeting calcitonin gene-related peptide (CGRP) revolutionized migraine treatment, still a substantial proportion of migraine patients do not respond satisfactorily to such a treatment, and new therapeutic targets are needed. Therefore, molecular studies on migraine pathogenesis are justified. Oxidative stress is implicated in migraine pathogenesis, as many migraine triggers are related to the production of reactive oxygen and nitrogen species (RONS). Migraine has been proposed as a superior mechanism of the brain to face oxidative stress resulting from energetic imbalance. However, the precise mechanism behind the link between migraine and oxidative stress is not known. Nociceptive primary afferent nerve fiber endings express ion channel receptors that change harmful stimuli into electric pain signals. Transient receptor potential cation channel subfamily A member 1 (TRPA1) is an ion channel that can be activated by oxidative stress products and stimulate the release of CGRP from nerve endings. It is a transmembrane protein with ankyrin repeats and conserved cysteines in its N-terminus embedded in the cytosol. TRPA1 may be a central element of the signaling pathway from oxidative stress and NO production to CGRP release, which may play a critical role in headache induction. In this narrative review, we present information on the role of oxidative stress in migraine pathogenesis and provide arguments that TRPA1 may be "a missing link" between oxidative stress and migraine and therefore a druggable target in this disease. [ABSTRACT FROM AUTHOR]

Electrical stimulation is a key tool in neuroscience, both in brain mapping studies and in many therapeutic applications such as cochlear, vestibular, and retinal neural implants. Due to safety considerations, stimulation is restricted to short biphasic pulses. Despite decades of research and development, neural implants lead to varying restoration of function in patients. In this study, we use computational modeling to provide an explanation for how pulsatile stimulation affects axonal channels and therefore leads to variability in restoration of neural responses. The phenomenological explanation is transformed into equations that predict induced firing rate as a function of pulse rate, pulse amplitude, and spontaneous firing rate. We show that these equations predict simulated responses to pulsatile stimulation with a variety of parameters as well as several features of experimentally recorded primate vestibular afferent responses to pulsatile stimulation. We then discuss the implications of these effects for improving clinical stimulation paradigms and electrical stimulation-based experiments. Pulsatile electrical stimulation is a common neuromodulation method, yet its effect on single neuron firing remains unclear. Here the authors show that pulses have multiple unintended but predictable effects on firing and discuss how they may be corrected when designing future neurotechnologies. [ABSTRACT FROM AUTHOR]

Introduction: Hearing decline stands as the most prevalent single sensory deficit associated with the aging process. Giving compelling evidence suggesting a protective effect associated with the efferent auditory system, the goal of our study was to characterize the age-related changes in the number of efferent medial olivocochlear (MOC) synapses regulating outer hair cell (OHC) activity compared with the number of afferent inner hair cell ribbon synapses in CBA/J mice over their lifespan. Methods: Organs of Corti of 3-month-old CBA/J mice were compared with mice aged between 10 and 20 months, grouped at 2-month intervals. For each animal, one ear was used to characterize the synapses between the efferent MOC fibers and the outer hair cells (OHCs), while the contralateral ear was used to analyze the ribbon synapses between inner hair cells (IHCs) and type I afferent nerve fibers of spiral ganglion neurons (SGNs). Each cochlea was separated in apical, middle, and basal turns, respectively. Results: The first significant age-related decline in afferent IHC-SGN ribbon synapses was observed in the basal cochlear turn at 14 months, the middle turn at 16 months, and the apical turn at 18 months of age. In contrast, efferent MOCOHC synapses in CBA/J mice exhibited a less pronounced loss due to aging which only became significant in the basal and middle turns of the cochlea by 20 months of age. Discussion: This study illustrates an age-related reduction on efferent MOC innervation of OHCs in CBA/J mice starting at 20 months of age. Our findings indicate that the morphological decline of efferent MOC-OHC synapses due to aging occurs notably later than the decline observed in afferent IHC-SGN ribbon synapses. [ABSTRACT FROM AUTHOR]

Sulfur dioxide (SO2), a common environmental and industrial air pollutant, possesses a potent effect in eliciting cough reflex, but the primary type of airway sensory receptors involved in its tussive action has not been clearly identified. This study was carried out to determine the relative roles of three major types of vagal bronchopulmonary afferents [slowly adapting receptors (SARs), rapidly adapting receptors (RARs), and C-fibers] in regulating the cough response to inhaled SO2. Our results showed that inhalation of SO2 (300 or 600 ppm for 8 min) evoked an abrupt and intense stimulatory effect on bronchopulmonary C-fibers, which continued for the entire duration of inhalation challenge and returned toward the baseline in 1–2 min after resuming room air-breathing in anesthetized and mechanically ventilated mice. In stark contrast, the same SO2 inhalation challenge generated a distinct and consistent inhibitory effect on both SARs and phasic RARs; their phasic discharges synchronized with respiratory cycles during the baseline (breathing room air) began to decline progressively within 1–3 min after the onset of SO2 inhalation, ceased completely before termination of the 8-min inhalation challenge, and then slowly returned toward the baseline after >40 min. In a parallel study in awake mice, inhalation of SO2 at the same concentration and duration as that in the nerve recording experiments evoked cough responses in a pattern and time course similar to that observed in the C-fiber responses. Based on these results, we concluded that stimulation of vagal bronchopulmonary C-fibers is primarily responsible for triggering the cough response to inhaled SO2. NEW & NOTEWORTHY: This study demonstrated that inhalation of a high concentration of sulfur dioxide, an irritant gas and common air pollutant, completely and reversibly inhibited the neural activities of both slowly adapting receptor and rapidly adapting receptor, two major types of mechanoreceptors in the lungs with their activities conducted by myelinated fibers. Furthermore, the results of this study suggested that stimulation of vagal bronchopulmonary C-fibers is primarily responsible for triggering the cough reflex responses to inhaled sulfur dioxide. [ABSTRACT FROM AUTHOR]

The transitional epithelial cells (urothelium) that line the lumen of the urinary bladder form a barrier between potentially harmful pathogens, toxins, and other bladder contents and the inner layers of the bladder wall. The urothelium, however, is not simply a passive barrier, as it can produce signaling factors, such as ATP, nitric oxide, prostaglandins, and other prostanoids, that can modulate bladder function. We investigated whether substances produced by the urothelium could directly modulate the contractility of the underlying urinary bladder smooth muscle. Force was measured in isolated strips of mouse urinary bladder with the urothelium intact or denuded. Bladder strips developed spontaneous tone and phasic contractions. In urothelium-intact strips, basal tone, as well as the frequency and amplitude of phasic contractions, were 25%, 32%, and 338% higher than in urothelium-denuded strips, respectively. Basal tone and phasic contractility in urothelium-intact bladder strips were abolished by the cyclooxygenase (COX) inhibitor indomethacin (10 µM) or the voltage-dependent Ca2+ channel blocker diltiazem (50 µM), whereas blocking neuronal sodium channels with tetrodotoxin (1 µM) had no effect. These results suggest that prostanoids produced in the urothelium enhance smooth muscle tone and phasic contractions by activating voltage-dependent Ca2+ channels in the underlying bladder smooth muscle. We went on to demonstrate that blocking COX inhibits the generation of transient pressure events in isolated pressurized bladders and greatly attenuates the afferent nerve activity during bladder filling, suggesting that urothelial prostanoids may also play a role in sensory nerve signaling. NEW & NOTEWORTHY: This paper provides evidence for the role of urothelial-derived prostanoids in maintaining tone in the urinary bladder during bladder filling, not only underscoring the role of the urothelium as more than a barrier but also contributing to active regulation of the urinary bladder. Furthermore, cyclooxygenase products greatly augment sensory nerve activity generated by bladder afferents during bladder filling and thus may play a role in perception of bladder fullness. [ABSTRACT FROM AUTHOR]

Purpose: Vestibular implant electrode positioning close to the afferent nerve fibers is considered to be key for effective and selective electrical stimulation. However, accurate positioning of vestibular implant electrodes inside the semicircular canal ampullae is challenging due to the inability to visualize the target during the surgical procedure. This study investigates the accuracy of a new surgical protocol with real-time fluoroscopy and intraoperative CT imaging, which facilitates electrode positioning during vestibular implant surgery. Methods: Single-center case-controlled cohort study with a historic control group at a tertiary referral center. Patients were implanted with a vestibulocochlear implant, using a combination of intraoperative fluoroscopy and cone beam CT imaging. The control group consisted of five patients who were previously implanted with the former implant prototype, without the use of intraoperative imaging. Electrode positioning was analyzed postoperatively with a high-resolution CT scan using 3D slicer software. The result was defined as accurate if the electrode position was within 1.5 mm of the center of the ampulla. Results: With the new imaging protocol, all electrodes could be positioned within a 1.5 mm range of the center of the ampulla. The accuracy was significantly higher in the study group with intraoperative imaging (21/21 electrodes) compared to the control group without intraoperative imaging (10/15 electrodes), (p = 0.008). Conclusion: The combined use of intraoperative fluoroscopy and CT imaging during vestibular implantation can improve the accuracy of electrode positioning. This might lead to better vestibular implant performance. [ABSTRACT FROM AUTHOR]

BACKGROUND The effectiveness of renal denervation (RDN) in reducing blood pressure and systemic sympathetic activity in hypertensive patients has been established. However, the underlying central mechanism remains unknown. This study aimed to investigate the role of RDN in regulating cardiovascular function via the central renin–angiotensin system (RAS) pathway. METHODS Ten-week-old spontaneously hypertensive rats (SHR) were subjected to selective afferent renal denervation (ADN) using capsaicin solution. We hypothesized that ADN would effectively reduce blood pressure and rebalance the RAS component of the paraventricular nucleus (PVN) in SHR. RESULTS The experimental results show that the ADN group exhibited significantly lower blood pressure, reduced systemic sympathetic activity, decreased chronic neuronal activation marker C-FOS expression in the PVN, and improved arterial baroreflex function, compared with the Sham group. Furthermore, ACE and AT1 protein expression was reduced while ACE2 and MAS protein expression was increased in the PVN of SHR after ADN. CONCLUSIONS These findings suggest that RDN may exert these beneficial effects through modulating the central RAS pathway. [ABSTRACT FROM AUTHOR]

Objectives: Early diagnosis of relative afferent pupillary defects (RAPDs) in patients with ocular trauma is crucial for timely management and improved outcomes. However, clinical examination can be challenging for patients with periorbital ecchymosis. This study aimed to compare the diagnostic accuracy of point‐of‐care ultrasound (POCUS) and clinical examination by emergency physicians for detecting RAPD in adult ocular trauma patients and to evaluate the proportion of RAPD in patients with ocular trauma who presented to the ED. Methods: This prospective cohort study was conducted at an academic emergency department in South India. Adult ocular trauma patients were assessed for RAPD using clinical examinations by emergency physicians and POCUS. The diagnostic accuracies of both methods were compared, with the ophthalmologist's final diagnosis serving as the gold standard. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for both techniques. Results: A total of 376 patients (median age, 35 years) were included in this study. RAPD was identified in 14.63% of the patients. The sensitivity and specificity of POCUS in detecting RAPD were 92.73% and 99.38%, respectively, which were higher than those of clinical examination, with a sensitivity of 81.82% and specificity of 99.07%. The PPV and NPV of the clinical examination were 93.75% and 96.95%, respectively, whereas the PPV and NPV of POCUS were 96.23% and 98.76%, respectively. POCUS accurately diagnosed RAPD in patients with periorbital ecchymosis. Conclusion: POCUS‐guided RAPD assessment proves to be a better diagnostic adjunct compared to clinical examination in patients with ocular trauma presenting to the emergency department. [ABSTRACT FROM AUTHOR]

A non-invasive and non-pharmacological approach is evaluated for the proprioceptive and postural improvement of PD subjects. The authors evaluated the effectiveness of a class I medical device according to EU regulation 745/2017 designed to develop the mechanism of action based on the modulation of action potentials, which occurs in prevalent pathways of the afferent peripheral nervous system efferent in subjects with spasticity. The present observational study, structured in a double-blind randomized manner, therefore, had the main aim of evaluating the ability of the device to improve on the motor and proprioceptive function of PD patients. This study was based on the instrumented gait analysis performed according to the Timed Up and Go (TUG) test procedure, as well as using a fall risk assessment in accordance with the Berg Balance Scale (BBS) procedures. This study involved 25 participants in the active group (no placebo) and 25 in the non-active group (placebo), the latter to whom non-functional devices were applied, but in every respect identical to the functional devices applied to the 25 patients in the no placebo group. Data analysis was conducted using statistical methodologies for statistics, the statistical significance of the results for the observed samples and the interdependence between the measured variables. The study of the mechanism of action based on the remodulation of action potentials was preliminary conducted through numerical modeling of the Hodgkin–Huxley axon, modified by introducing the influence of the capacitive device applied in clinical tests into the validated model to target the dielectric properties of materials constituting the passive sensor. The use of the neuromodulation device promises observable improvements in motor function among PD patients, including increased limb mobility and greater postural stability. [ABSTRACT FROM AUTHOR]

The thalamic reticular nucleus (TRN) serves as an important node between the thalamus and neocortex, regulating thalamocortical rhythms and sensory processing in a state dependent manner. Disruptions in TRN circuitry also figures prominently in several neurodevelopmental disorders including epilepsy, autism, and attentional defects. An understanding of how and when connections between TRN and 1st order thalamic nuclei, such as the dorsal lateral geniculate nucleus (dLGN), develop is lacking. We used the mouse visual thalamus as a model system to study the organization, pattern of innervation and functional responses between TRN and the dLGN. Genetically modified mouse lines were used to visualize and target the feedforward and feedback components of these intra-thalamic circuits and to understand how peripheral input from the retina impacts their development. Retrograde tracing of thalamocortical (TC) afferents through TRN revealed that the modality-specific organization seen in the adult, is present at perinatal ages and seems impervious to the loss of peripheral input. To examine the formation and functional maturation of intrathalamic circuits between the visual sector of TRN and dLGN, we examined when projections from each nuclei arrive, and used an acute thalamic slice preparation along with optogenetic stimulation to assess the maturation of functional synaptic responses. Although thalamocortical projections passed through TRN at birth, feedforward axon collaterals determined by vGluT2 labeling, emerged during the second postnatal week, increasing in density through the third week. Optogenetic stimulation of TC axon collaterals in TRN showed infrequent, weak excitatory responses near the end of week 1. During weeks 2–4, responses became more prevalent, grew larger in amplitude and exhibited synaptic depression during repetitive stimulation. Feedback projections from visual TRN to dLGN began to innervate dLGN as early as postnatal day 2 with weak inhibitory responses emerging during week 1. During week 2–4, inhibitory responses continued to grow larger, showing synaptic depression during repetitive stimulation. During this time TRN inhibition started to suppress TC spiking, having its greatest impact by week 4–6. Using a mutant mouse that lacks retinofugal projections revealed that the absence of retinal input led to an acceleration of TRN innervation of dLGN but had little impact on the development of feedforward projections from dLGN to TRN. Together, these experiments reveal how and when intrathalamic connections emerge during early postnatal ages and provide foundational knowledge to understand the development of thalamocortical network dynamics as well as neurodevelopmental diseases that involve TRN circuitry. [ABSTRACT FROM AUTHOR]

The optic afferent nervous system (OANS) plays a significant role in generating vision and circadian behaviors based on light detection and signals from the endocrine system. However, the bionic simulation of this photochemically mediated behavior is still a challenge for neuromorphic devices. Herein, stimuli of neurotransmitters at ultralow concentrations and illumination are coupled to artificial synapses with the aid of biofunctionalized heterojunction and tunneling to successfully simulate a circadian neural response. Furthermore, the mechanisms underlying the photosensitive synaptic current in response to stimuli are described. Interestingly, this OANS is demonstrated to be capable of mimicking normal and abnormal circadian learnability by combining the measured synaptic current with a three‐layer spike neural network. Strong theoretical and experimental evidence, as well as applications, are provided for the proposed biomimetic OANS to demonstrate that it can reproduce biological circadian behavior, thus establishing it as a promising candidate for future neuromorphic intelligent robots. [ABSTRACT FROM AUTHOR]

The anterior (DA) and posterior parts of the deltoid (DP) show alternating contraction during shoulder flexion and extension movements. It is expected that an inhibitory spinal reflex between the DA and DP exists. In this study, spinal reflexes between the DA and DP were examined in healthy human subjects using post-stimulus time histogram (PSTH) and electromyogram averaging (EMG-A). Electrical conditioning stimulation was delivered to the axillary nerve branch that innervates the DA (DA nerve) and DP (DP nerve) with the intensity below the motor threshold. In the PSTH study, the stimulation to the DA and DP nerves inhibited (decrease in the firing probability) 31 of 54 DA motor units and 31 of 51 DP motor units. The inhibition was not provoked by cutaneous stimulation. The central synaptic delay of the inhibition between the DA and DP nerves was 1.5 ± 0.5 ms and 1.4 ± 0.4 ms (mean ± SD) longer than those of the homonymous facilitation of the DA and DP, respectively. In the EMG-A study, conditioning stimulation to the DA and DP nerves inhibited the rectified and averaged EMG of the DP and DA, respectively. The inhibition diminished with tonic vibration stimulation to the DA and DP and recovered 20–30 min after vibration removal. These findings suggest that oligo(di or tri)-synaptic inhibition mediated by group Ia afferents between the DA and DP exists in humans. [ABSTRACT FROM AUTHOR]

Understanding how the gut communicates with the brain, via sensory nerves, is of significant interest to medical science. Enteroendocrine cells (EEC) that line the mucosa of the gastrointestinal tract release neurochemicals, including the largest quantity of 5-hydroxytryptamine (5-HT). How the release of substances, like 5-HT, from enterochromaffin (EC) cells activates vagal afferent nerve endings is unresolved. We performed anterograde labelling from nodose ganglia in vivo and identified vagal afferent axons and nerve endings in the mucosa of whole-mount full-length preparations of mouse colon. We then determined the spatial relationship between mucosal-projecting vagal afferent nerve endings and EC cells in situ using 3D imaging. The mean distances between vagal afferent nerve endings in the mucosa, or nearest varicosities along vagal afferent axon branches, and the nearest EC cell were 29.6 ± 19.2 μm (n = 107, N = 6) and 25.7 ± 15.2 μm (n = 119, N = 6), respectively. No vagal afferent endings made close contacts with EC cells. The distances between EC cells and vagal afferent endings are many hundreds of times greater than known distances between pre- and post-synaptic membranes (typically 10–20 nm) that underlie synaptic transmission in vertebrates. The absence of any close physical contacts between 5-HT-containing EC cells and vagal afferent nerve endings in the mucosa leads to the inescapable conclusion that the mechanism by which 5-HT release from ECs in the colonic mucosa occurs in a paracrine fashion, to activate vagal afferents. [ABSTRACT FROM AUTHOR]

The authors present the life and art of Giuseppe Dagnini, a renowned Italian physician who was born in Bologna in 1866. He was the chief of the Maggiore Hospital in Bologna and authored valuable scientific works on the trigemino-cardiac reflex which is still applied in modern clinical practice. Dr. Dagnini firstly described the reflex in 1908 postulating that stimulation of one of the 3 branches of the trigeminal nerve triggers the afferent pathway in lowering heart rate. The authors also provide a modern outlook on the clinical implications of the TCR in neurosurgery, neuroanesthesia, and other medical specialties. [ABSTRACT FROM AUTHOR]

Objective: Phenylethanolamine N‐methyltransferase (PNMT)‐expressing neurons in the nucleus tractus solitarii (NTS) contribute to the regulation of autonomic functions. However, the neural circuits linking these neurons to other brain regions remain unclear. This study aims to investigate the connectivity mechanisms of the PNMT‐expressing neurons in the NTS (NTSPNMT neurons). Methods: The methodologies employed in this study included a modified rabies virus‐based retrograde neural tracing technique, conventional viral anterograde tracing, and immunohistochemical staining procedures. Results: A total of 43 upstream nuclei projecting to NTSPNMT neurons were identified, spanning several key brain regions including the medulla oblongata, pons, midbrain, cerebellum, diencephalon, and telencephalon. Notably, dense projections to the NTSPNMT neurons were observed from the central amygdaloid nucleus, paraventricular nucleus of the hypothalamus, area postrema, and the gigantocellular reticular nucleus. In contrast, the ventrolateral medulla, lateral parabrachial nucleus, and lateral hypothalamic area were identified as the primary destinations for axon terminals originating from NTSPNMT neurons. Additionally, reciprocal projections were evident among 21 nuclei, primarily situated within the medulla oblongata. Conclusion: Our research findings demonstrate that NTSPNMT neurons form extensive connections with numerous nuclei, emphasizing their essential role in the homeostatic regulation of vital autonomic functions. [ABSTRACT FROM AUTHOR]

Corticotropin-releasing hormone (CRH) and capsaicin-sensitive afferent neurons with efferent-like function (CSN) make important contributions to the regulation of gastrointestinal tract (GIT) functions and gastroprotection. The objective of this review was to analyze published data, including the results of our own research, on the interaction of CRH and CSN in providing gastroprotection and in the regulation of GIT functions, with a focus on the most studied interaction – the regulation of GIT motor function. Based on our own research data, we discuss the possibility that CSN contribute to mediating the gastroprotective effect of CRH and, conversely, the possibility that CRH has a role in ensuring the gastroprotective effect of capsaicin, which activates CSN. The contributions of glucocorticoid hormones to mediating the gastroprotective actions of CRH and the compensatory gastroprotective role of these hormones in conditions of functional exclusion of CSN are considered. [ABSTRACT FROM AUTHOR]

This article discusses the development of long-acting local anesthetics for postoperative pain management. The use of opioids for pain relief can lead to adverse effects, so researchers have been exploring alternative options. The article explores different strategies, including quaternary lidocaine derivatives, voltage-gated sodium channel antagonists, site-1 sodium channel blockers, and controlled-release local anesthetics. While some of these options have shown promise, there are still limitations and challenges to overcome before they can be widely used in clinical practice. [Extracted from the article]

The article titled "Elegy for Neural Coding in Understanding Cognition: Brains are Not Computers" challenges the prevailing belief that the brain functions like a computer. The author argues that the metaphor of neural coding, which divorces the brain from its causal structure, is problematic and does not adequately explain cognitive events, thinking, and memory. The article highlights the complexity and randomness of neural processes and emphasizes that human behavior cannot be explained solely through information processing. The author suggests that researchers should move away from the information processing metaphor and focus on observing and measuring phenomena instead. [Extracted from the article]