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Neuron Feb 2022The vagus nerve is an indispensable body-brain connection that controls vital aspects of autonomic physiology like breathing, heart rate, blood pressure, and gut... (Review)
Review
The vagus nerve is an indispensable body-brain connection that controls vital aspects of autonomic physiology like breathing, heart rate, blood pressure, and gut motility, reflexes like coughing and swallowing, and survival behaviors like feeding, drinking, and sickness responses. Classical physiological studies and recent molecular/genetic approaches have revealed a tremendous diversity of vagal sensory neuron types that innervate different internal organs, with many cell types remaining poorly understood. Here, we review the state of knowledge related to vagal sensory neurons that innervate the respiratory, cardiovascular, and digestive systems. We focus on cell types and their response properties, physiological/behavioral roles, engaged neural circuits and, when possible, sensory receptors. We are only beginning to understand the signal transduction mechanisms used by vagal sensory neurons and upstream sentinel cells, and future studies are needed to advance the field of interoception to the level of mechanistic understanding previously achieved for our external senses.
Topics: Interoception; Reflex; Sensation; Sensory Receptor Cells; Vagus Nerve
PubMed: 35051375
DOI: 10.1016/j.neuron.2021.12.020 -
Journal of Biomedical Science Dec 2021Addictive drugs are habit-forming. Addiction is a learned behavior; repeated exposure to addictive drugs can stamp in learning. Dopamine-depleted or dopamine-deleted... (Review)
Review
Addictive drugs are habit-forming. Addiction is a learned behavior; repeated exposure to addictive drugs can stamp in learning. Dopamine-depleted or dopamine-deleted animals have only unlearned reflexes; they lack learned seeking and learned avoidance. Burst-firing of dopamine neurons enables learning-long-term potentiation (LTP)-of search and avoidance responses. It sets the stage for learning that occurs between glutamatergic sensory inputs and GABAergic motor-related outputs of the striatum; this learning establishes the ability to search and avoid. Independent of burst-firing, the rate of single-spiking-or "pacemaker firing"-of dopaminergic neurons mediates motivational arousal. Motivational arousal increases during need states and its level determines the responsiveness of the animal to established predictive stimuli. Addictive drugs, while usually not serving as an external stimulus, have varying abilities to activate the dopamine system; the comparative abilities of different addictive drugs to facilitate LTP is something that might be studied in the future.
Topics: Animals; Appetitive Behavior; Avoidance Learning; Behavior, Addictive; Dopamine; Dopaminergic Neurons; Learning; Long-Term Potentiation; Mice; Rats; Reflex
PubMed: 34852810
DOI: 10.1186/s12929-021-00779-7 -
Nature Oct 2021Somatosensory autonomic reflexes allow electroacupuncture stimulation (ES) to modulate body physiology at distant sites (for example, suppressing severe systemic...
Somatosensory autonomic reflexes allow electroacupuncture stimulation (ES) to modulate body physiology at distant sites (for example, suppressing severe systemic inflammation). Since the 1970s, an emerging organizational rule about these reflexes has been the presence of body-region specificity. For example, ES at the hindlimb ST36 acupoint but not the abdominal ST25 acupoint can drive the vagal-adrenal anti-inflammatory axis in mice. The neuroanatomical basis of this somatotopic organization is, however, unknown. Here we show that PROKR2-marked sensory neurons, which innervate the deep hindlimb fascia (for example, the periosteum) but not abdominal fascia (for example, the peritoneum), are crucial for driving the vagal-adrenal axis. Low-intensity ES at the ST36 site in mice with ablated PROKR2-marked sensory neurons failed to activate hindbrain vagal efferent neurons or to drive catecholamine release from adrenal glands. As a result, ES no longer suppressed systemic inflammation induced by bacterial endotoxins. By contrast, spinal sympathetic reflexes evoked by high-intensity ES at both ST25 and ST36 sites were unaffected. We also show that optogenetic stimulation of PROKR2-marked nerve terminals through the ST36 site is sufficient to drive the vagal-adrenal axis but not sympathetic reflexes. Furthermore, the distribution patterns of PROKR2 nerve fibres can retrospectively predict body regions at which low-intensity ES will or will not effectively produce anti-inflammatory effects. Our studies provide a neuroanatomical basis for the selectivity and specificity of acupoints in driving specific autonomic pathways.
Topics: Acupuncture Points; Adrenal Glands; Animals; Autonomic Nervous System; Electroacupuncture; Hindlimb; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Reflex; Vagus Nerve
PubMed: 34646018
DOI: 10.1038/s41586-021-04001-4 -
Cell Reports. Medicine Jul 2022The cholinergic anti-inflammatory pathway is the efferent arm of the inflammatory reflex, a neural circuit through which the CNS can modulate peripheral immune... (Review)
Review
The cholinergic anti-inflammatory pathway is the efferent arm of the inflammatory reflex, a neural circuit through which the CNS can modulate peripheral immune responses. Signals communicated via the vagus and splenic nerves use acetylcholine, produced by Choline acetyltransferase (ChAT)+ T cells, to downregulate the inflammatory actions of macrophages expressing α7 nicotinic receptors. Pre-clinical studies using transgenic animals, cholinergic agonists, vagotomy, and vagus nerve stimulation have demonstrated this pathway's role and therapeutic potential in numerous inflammatory diseases. In this review, we summarize what is understood about the inflammatory reflex. We also demonstrate how pre-clinical findings are being translated into promising clinical trials, and we draw particular attention to innovative bioelectronic methods of harnessing the cholinergic anti-inflammatory pathway for clinical use.
Topics: Animals; Neuroimmunomodulation; Reflex; Vagus Nerve; Vagus Nerve Stimulation; alpha7 Nicotinic Acetylcholine Receptor
PubMed: 35858588
DOI: 10.1016/j.xcrm.2022.100696 -
Current Biology : CB Sep 2020Many of us know about stretch reflexes from the doctor's office, when a physician taps the tendon near our kneecap to elicit a quick knee extension. This procedure is...
Many of us know about stretch reflexes from the doctor's office, when a physician taps the tendon near our kneecap to elicit a quick knee extension. This procedure is used as a diagnostic tool to determine the integrity of the spinal cord and the extension response it elicits may seem otherwise useless. In fact, the tendon tap taps into one aspect of a critical building block of mammalian motor control, the stretch reflexes. Stretch reflexes are often thought to quickly resist unexpected changes in muscle length via a very simple circuit in the spinal cord, and this is one circuit that the tendon tap engages. It turns out, however, that stretch reflexes support a myriad of functions and are highly flexible. Under naturalistic conditions, stretch reflexes are shaped by peripheral physiology and engage neural circuits spanning the spinal cord, brainstem and cerebral cortex. In this Primer, we outline what is currently known about stretch reflex function and its underlying mechanisms, with a specific focus on how the cascade of nested responses collectively known as stretch reflexes interact with and build off of one another to support real-world motor behavior.
Topics: Humans; Motor Activity; Muscle, Skeletal; Reaction Time; Reflex, Stretch; Tendons
PubMed: 32961152
DOI: 10.1016/j.cub.2020.07.092 -
Nature Dec 2020Henry Miller stated that "to relieve a full bladder is one of the great human joys". Urination is critically important in health and ailments of the lower urinary tract...
Henry Miller stated that "to relieve a full bladder is one of the great human joys". Urination is critically important in health and ailments of the lower urinary tract cause high pathological burden. Although there have been advances in understanding the central circuitry in the brain that facilitates urination, there is a lack of in-depth mechanistic insight into the process. In addition to central control, micturition reflexes that govern urination are all initiated by peripheral mechanical stimuli such as bladder stretch and urethral flow. The mechanotransduction molecules and cell types that function as the primary stretch and pressure detectors in the urinary tract mostly remain unknown. Here we identify expression of the mechanosensitive ion channel PIEZO2 in lower urinary tract tissues, where it is required for low-threshold bladder-stretch sensing and urethral micturition reflexes. We show that PIEZO2 acts as a sensor in both the bladder urothelium and innervating sensory neurons. Humans and mice lacking functional PIEZO2 have impaired bladder control, and humans lacking functional PIEZO2 report deficient bladder-filling sensation. This study identifies PIEZO2 as a key mechanosensor in urinary function. These findings set the foundation for future work to identify the interactions between urothelial cells and sensory neurons that control urination.
Topics: Animals; Female; Humans; Ion Channels; Mechanotransduction, Cellular; Mice; Pressure; Reflex; Sensory Receptor Cells; Urinary Bladder; Urinary Tract; Urination; Urothelium
PubMed: 33057202
DOI: 10.1038/s41586-020-2830-7 -
Physiological Research Mar 2020Since the recognition of angiotensin-converting enzyme inhibitors (ACEIs)-induced cough, drug has been considered as a potential cause of chronic cough. This review... (Review)
Review
Since the recognition of angiotensin-converting enzyme inhibitors (ACEIs)-induced cough, drug has been considered as a potential cause of chronic cough. This review presents recent knowledge on drug-induced coughs in patients with chronic cough. The focus is placed on ACEIs, for which there are a multitude of studies documenting their associations with cough. Additional drugs are discussed for which there are reports of cough as a side effect of treatment, and the potential mechanisms of these effects are discussed.
Topics: Analgesics, Opioid; Angiotensin-Converting Enzyme Inhibitors; Animals; Calcium Channel Blockers; Chronic Disease; Cough; Fentanyl; Humans; Reflex
PubMed: 32228014
DOI: 10.33549/physiolres.934406 -
La Tunisie Medicale Dec 2023A relatively common oral health problem, gag reflex is a clinical challenge during dentures fabrication. In the current literature several techniques have been described...
A relatively common oral health problem, gag reflex is a clinical challenge during dentures fabrication. In the current literature several techniques have been described regarding this clinical condition. The latter use either psychological, pharmacological and prosthetic therapies to treat these patients. The purpose of this case report is to highlight an original prosthetic strategy which consists on a progressive lengthening of the maxillary complete prosthesis allowing a patient with acute gag reflex to adapt to the denture palatal extension.
Topics: Humans; Denture, Complete, Upper; Denture Design; Denture Retention; Reflex
PubMed: 38477203
DOI: No ID Found -
Clinical Neurophysiology : Official... May 2024Blinking is a motor act characterized by the sequential closing and opening of the eyelids, which is achieved through the reciprocal activation of the orbicularis oculi... (Review)
Review
Blinking is a motor act characterized by the sequential closing and opening of the eyelids, which is achieved through the reciprocal activation of the orbicularis oculi and levator palpebrae superioris muscles. This stereotyped movement can be triggered reflexively, occur spontaneously, or voluntarily initiated. During each type of blinking, the neural control of the antagonistic interaction between the orbicularis oculi and levator palpebrae superioris muscles is governed by partially overlapping circuits distributed across cortical, subcortical, and brainstem structures. This paper provides a comprehensive overview of the anatomical and physiological foundations underlying the neural control of blinking. We describe the infra-nuclear apparatus, as well as the supra-nuclear control mechanisms, i.e., how cortical, subcortical, and brainstem structures regulate and coordinate the different types of blinking.
Topics: Humans; Blinking; Animals; Brain Stem; Eyelids
PubMed: 38447495
DOI: 10.1016/j.clinph.2024.02.023 -
Experimental Brain Research Mar 2022The purpose of this study was to examine corticospinal modulation of spinal reflex excitability, by determining the effect of transcranial magnetic stimulation (TMS) on...
The purpose of this study was to examine corticospinal modulation of spinal reflex excitability, by determining the effect of transcranial magnetic stimulation (TMS) on soleus H-reflexes while they were almost completely suppressed by lower extremity vibration. In 15 healthy adults, a novel method of single-limb vibration (0.6 g, 30 Hz, 0.33 mm displacement) was applied to the non-dominant leg. Soleus muscle responses were examined in six stimulation conditions: (1) H-reflex elicited by tibial nerve stimulation, (2) tibial nerve stimulation during vibration, (3) subthreshold TMS, (4) subthreshold TMS during vibration, (5) tibial nerve stimulation 10 ms after a subthreshold TMS pulse, and (6) tibial nerve stimulation 10 ms after a subthreshold TMS pulse, during vibration. With or without vibration, subthreshold TMS produced no motor evoked potentials and had no effect on soleus electromyography (p > 0.05). In the absence of vibration, H-reflex amplitudes were not affected by subthreshold TMS conditioning (median (md) 35, interquartile range (IQ) 18-56 vs. md 46, IQ 22-59% of the maximal M wave (Mmax), p > 0.05). During vibration, however, unconditioned H-reflexes were nearly abolished, and a TMS conditioning pulse increased the H-reflex more than fourfold (md 0.3, IQ 0.1-0.7 vs. md 2, IQ 0.9-5.0% of Mmax, p < 0.008). Limb vibration alone had no significant effect on corticospinal excitability. In the absence of vibration, a subthreshold TMS pulse did not influence the soleus H-reflex. During limb vibration, however, while the H-reflex was almost completely suppressed, a subthreshold TMS pulse partially restored the H-reflex. This disinhibition of the H-reflex by a corticospinal signal may represent a mechanism involved in the control of voluntary movement. Corticospinal signals that carry the descending motor command may also reduce presynaptic inhibition, temporarily increasing the impact of sensory inputs on motoneuron activation.
Topics: Adult; Depression; Electric Stimulation; Electromyography; Evoked Potentials, Motor; H-Reflex; Humans; Muscle, Skeletal; Transcranial Magnetic Stimulation; Vibration
PubMed: 35044475
DOI: 10.1007/s00221-022-06306-w