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Cardiovascular Research Oct 2023The brain controls the heart by dynamic recruitment and withdrawal of cardiac parasympathetic (vagal) and sympathetic activity. Autonomic control is essential for the...
AIMS
The brain controls the heart by dynamic recruitment and withdrawal of cardiac parasympathetic (vagal) and sympathetic activity. Autonomic control is essential for the development of cardiovascular responses during exercise, however, the patterns of changes in the activity of the two autonomic limbs, and their functional interactions in orchestrating physiological responses during exercise, are not fully understood. The aim of this study was to characterize changes in vagal parasympathetic drive in response to exercise and exercise training by directly recording the electrical activity of vagal preganglionic neurons in experimental animals (rats).
METHODS AND RESULTS
Single unit recordings were made using carbon-fibre microelectrodes from the populations of vagal preganglionic neurons of the nucleus ambiguus (NA) and the dorsal vagal motor nucleus of the brainstem. It was found that (i) vagal preganglionic neurons of the NA and the dorsal vagal motor nucleus are strongly activated during bouts of acute exercise, and (ii) exercise training markedly increases the resting activity of both populations of vagal preganglionic neurons and augments the excitatory responses of NA neurons during exercise.
CONCLUSIONS
These data show that central vagal drive increases during exercise and provide the first direct neurophysiological evidence that exercise training increases vagal tone. The data argue against the notion of exercise-induced central vagal withdrawal during exercise. We propose that robust increases in the activity of vagal preganglionic neurons during bouts of exercise underlie activity-dependent plasticity, leading to higher resting vagal tone that confers multiple health benefits associated with regular exercise.
Topics: Rats; Animals; Autonomic Fibers, Preganglionic; Vagus Nerve; Heart; Neurons; Medulla Oblongata
PubMed: 37516977
DOI: 10.1093/cvr/cvad115 -
Comprehensive Physiology Apr 2015The sympathetic nervous system comprises one half of the autonomic nervous system and participates in maintaining homeostasis and enabling organisms to respond in an... (Review)
Review
The sympathetic nervous system comprises one half of the autonomic nervous system and participates in maintaining homeostasis and enabling organisms to respond in an appropriate manner to perturbations in their environment, either internal or external. The sympathetic preganglionic neurons (SPNs) lie within the spinal cord and their axons traverse the ventral horn to exit in ventral roots where they form synapses onto postganglionic neurons. Thus, these neurons are the last point at which the central nervous system can exert an effect to enable changes in sympathetic outflow. This review considers the degree of complexity of sympathetic control occurring at the level of the spinal cord. The morphology and targets of SPNs illustrate the diversity within this group, as do their diverse intrinsic properties which reveal some functional significance of these properties. SPNs show high degrees of coupled activity, mediated through gap junctions, that enables rapid and coordinated responses; these gap junctions contribute to the rhythmic activity so critical to sympathetic outflow. The main inputs onto SPNs are considered; these comprise afferent, descending, and interneuronal influences that themselves enable functionally appropriate changes in SPN activity. The complexity of inputs is further demonstrated by the plethora of receptors that mediate the different responses in SPNs; their origins and effects are plentiful and diverse. Together these different inputs and the intrinsic and coupled activity of SPNs result in the rhythmic nature of sympathetic outflow from the spinal cord, which has a variety of frequencies that can be altered in different conditions.
Topics: Animals; Autonomic Fibers, Preganglionic; Central Pattern Generators; Gap Junctions; Humans; Models, Neurological; Spinal Cord; Sympathetic Nervous System; Synapses
PubMed: 25880515
DOI: 10.1002/cphy.c140020 -
Neural Regeneration Research Sep 2017Autonomic dysreflexia (AD) is a serious cardiovascular disorder in patients with spinal cord injury (SCI). The primary underlying cause of AD is loss of supraspinal... (Review)
Review
Autonomic dysreflexia (AD) is a serious cardiovascular disorder in patients with spinal cord injury (SCI). The primary underlying cause of AD is loss of supraspinal control over sympathetic preganglionic neurons (SPNs) caudal to the injury, which renders the SPNs hyper-responsive to stimulation. Central maladaptive plasticity, including C-fiber sprouting and propriospinal fiber proliferation exaggerates noxious afferent transmission to the SPNs, causing them to release massive sympathetic discharges that result in severe hypertensive episodes. In parallel, upregulated peripheral vascular sensitivity following SCI exacerbates the hypertensive response by augmenting gastric and pelvic vasoconstriction. Currently, the majority of clinically employed treatments for AD involve anti-hypertensive medications and Botox injections to the bladder. Although these approaches mitigate the severity of AD, they only yield transient effects and target the effector organs, rather than addressing the primary issue of central sympathetic dysregulation. As such, strategies that aim to restore supraspinal reinnervation of SPNs to improve cardiovascular sympathetic regulation are likely more effective for AD. Recent pre-clinical investigations show that cell transplantation therapy is efficacious in reestablishing spinal sympathetic connections and improving hemodynamic performance, which holds promise as a potential therapeutic approach.
PubMed: 29089975
DOI: 10.4103/1673-5374.215241 -
Clinical Autonomic Research : Official... Feb 2024We have re-evaluated the anatomical arguments that underlie the division of the spinal visceral outflow into sympathetic and parasympathetic divisions. (Review)
Review
PURPOSE
We have re-evaluated the anatomical arguments that underlie the division of the spinal visceral outflow into sympathetic and parasympathetic divisions.
METHODOLOGY
Using a systematic literature search, we mapped the location of catecholaminergic neurons throughout the mammalian peripheral nervous system. Subsequently, a narrative method was employed to characterize segment-dependent differences in the location of preganglionic cell bodies and the composition of white and gray rami communicantes.
RESULTS AND CONCLUSION
One hundred seventy studies were included in the systematic review, providing information on 389 anatomical structures. Catecholaminergic nerve fibers are present in most spinal and all cranial nerves and ganglia, including those that are known for their parasympathetic function. Along the entire spinal autonomic outflow pathways, proximal and distal catecholaminergic cell bodies are common in the head, thoracic, and abdominal and pelvic region, which invalidates the "short-versus-long preganglionic neuron" argument. Contrary to the classically confined outflow levels T1-L2 and S2-S4, preganglionic neurons have been found in the resulting lumbar gap. Preganglionic cell bodies that are located in the intermediolateral zone of the thoracolumbar spinal cord gradually nest more ventrally within the ventral motor nuclei at the lumbar and sacral levels, and their fibers bypass the white ramus communicans and sympathetic trunk to emerge directly from the spinal roots. Bypassing the sympathetic trunk, therefore, is not exclusive for the sacral outflow. We conclude that the autonomic outflow displays a conserved architecture along the entire spinal axis, and that the perceived differences in the anatomy of the autonomic thoracolumbar and sacral outflow are quantitative.
Topics: Animals; Humans; Neurons; Sympathetic Nervous System; Ganglia, Sympathetic; Spinal Cord; Sacrum; Mammals
PubMed: 38403748
DOI: 10.1007/s10286-024-01023-6 -
Clinical Autonomic Research : Official... Jun 2015In mammals, sweating is a multifunctional response that aids in locomotion, thermal regulation, self-protection, and communication of psychological state. Humans possess... (Review)
Review
In mammals, sweating is a multifunctional response that aids in locomotion, thermal regulation, self-protection, and communication of psychological state. Humans possess three types of sweat glands (apocrine, eccrine, and apoeccrine) that are differentially distributed on the body surface and make unique contributions to these distinct functions of the sweating response. In humans, eccrine glands, which are widely distributed on hairy skin, play an important role in thermoregulation. They are also found on the glabrous skin of the palm and sole, where they are not usually activated by heat, but rather by deep respiration, mental stress, and local tactile stimulation. Sweating on the palm and sole, so-called "emotional sweating", acts to prevent slippage while grasping or performing a delicate task using the fingertips. Although the central pathways of emotional sweating are not yet elucidated in detail, it is thought that the amygdala, cingulate cortex, and medulla participate via efferent fibers that descend through the spinal cord and connect to preganglionic sympathetic neurons in the nucleus intermediolateralis. The limbic system, including the amygdala and cingulate cortex, is critical for emotional processing and many cognitive functions. Thus, measurement of sweat output on the palm or sole is useful for evaluating sympathetic function and limbic activity in autonomic and psychiatric disorders.
Topics: Animals; Autonomic Nervous System; Foot; Hand; Humans; Sweat Gland Diseases; Sweat Glands; Sweating
PubMed: 25894655
DOI: 10.1007/s10286-015-0282-1 -
Cell Jun 2024Many behaviors require the coordinated actions of somatic and autonomic functions. However, the underlying mechanisms remain elusive. By opto-stimulating different...
Many behaviors require the coordinated actions of somatic and autonomic functions. However, the underlying mechanisms remain elusive. By opto-stimulating different populations of descending spinal projecting neurons (SPNs) in anesthetized mice, we show that stimulation of excitatory SPNs in the rostral ventromedial medulla (rVMM) resulted in a simultaneous increase in somatomotor and sympathetic activities. Conversely, opto-stimulation of rVMM inhibitory SPNs decreased both activities. Anatomically, these SPNs innervate both sympathetic preganglionic neurons and motor-related regions in the spinal cord. Fiber-photometry recording indicated that the activities of rVMM SPNs correlate with different levels of muscle and sympathetic tone during distinct arousal states. Inhibiting rVMM excitatory SPNs reduced basal muscle and sympathetic tone, impairing locomotion initiation and high-speed performance. In contrast, silencing the inhibitory population abolished muscle atonia and sympathetic hypoactivity during rapid eye movement (REM) sleep. Together, these results identify rVMM SPNs as descending spinal projecting pathways controlling the tone of both the somatomotor and sympathetic systems.
Topics: Animals; Male; Mice; Locomotion; Medulla Oblongata; Mice, Inbred C57BL; Motor Neurons; Neurons; Sleep, REM; Spinal Cord; Sympathetic Nervous System; Behavior, Animal; Cell Count; Muscle, Skeletal
PubMed: 38733990
DOI: 10.1016/j.cell.2024.04.022 -
Journal of Applied Physiology... Dec 2023Cervical spinal cord injury interrupts supraspinal pathways innervating thoracic sympathetic preganglionic neurons and results in cardiovascular dysfunction. Both...
Cervical spinal cord injury interrupts supraspinal pathways innervating thoracic sympathetic preganglionic neurons and results in cardiovascular dysfunction. Both respiratory and locomotor functions were also impaired due to damages of motoneuron pools controlling respiratory and forelimb muscles, respectively. However, no study has investigated autonomic and somatic motor functions in the same animal model. The present study aimed to establish a cervical spinal cord injury model to evaluate cardiorespiratory response and locomotor activity in unanesthetized rats. Cardiovascular response and respiratory behavior following laminectomy or cervical spinal contusion were measured using noninvasive blood pressure analyzer and plethysmography systems, respectively. Locomotor activity was evaluated by an open-field test and a locomotor rating scale. The results demonstrated that mean arterial blood pressure and heart rate were significantly reduced in contused rats compared with uninjured rats at the acute injured stage. Tidal volume was also significantly reduced during the acute and subchronic stages. Moreover, locomotor function was severely impaired, evidenced by decreasing moving ability and locomotor rating scores from the acute to chronic injured stages. Retrograde neurotracer results revealed that cervical spinal cord injury caused a reduction in number of phrenic and triceps motoneurons. Immunofluorescence staining revealed a significant attenuation of serotonergic, noradrenergic, glutamatergic, and GABAergic fibers innervating the thoracic sympathetic preganglionic neurons in chronically contused rats. These results revealed the pathological mechanism underlying the comorbidity of cardiorespiratory and locomotor dysfunction following cervical spinal cord injury. We proposed that this animal model can be used to evaluate the therapeutic efficacy of potential strategies to improve different physiological functions. The present study establishes a preclinical rodent model to comprehensively investigate physiological functions under unanesthetized condition following cervical spinal cord contusion. The results demonstrated that cervical spinal cord contusion is associated with impairments in cardiovascular, respiratory, and locomotor function. Respiratory and forelimb motoneurons and neurochemical innervations of sympathetic preganglionic neurons were damaged following injury. This animal model can be used to evaluate the therapeutic efficacy of potential strategies to improve different physiological functions.
Topics: Rats; Animals; Rats, Sprague-Dawley; Cervical Cord; Spinal Cord Injuries; Spinal Cord; Comorbidity; Cervical Vertebrae
PubMed: 37855033
DOI: 10.1152/japplphysiol.00473.2023 -
Hypertension (Dallas, Tex. : 1979) Jul 2024The NET (norepinephrine transporter) is situated in the prejunctional plasma membrane of noradrenergic neurons. It is responsible for >90% of the norepinephrine uptake... (Review)
Review
The NET (norepinephrine transporter) is situated in the prejunctional plasma membrane of noradrenergic neurons. It is responsible for >90% of the norepinephrine uptake that is released in the autonomic neuroeffector junction. Inhibitors of this cell membrane transporter, known as norepinephrine reuptake inhibitors (NRIs), are commercially available for the treatment of depression and attention deficit hyperactivity disorder. These agents increase norepinephrine levels, potentiating its action in preganglionic and postganglionic adrenergic neurons, the latter through activation of α-1 adrenoreceptors. Previous studies found that patients with neurogenic orthostatic hypotension can improve standing blood pressure and reduce symptoms of neurogenic orthostatic hypotension after a single administration of the selective NRI atomoxetine. This effect was primarily observed in patients with impaired central autonomic pathways with otherwise normal postganglionic sympathetic fibers, known as multiple system atrophy. Likewise, patients with normal or high norepinephrine levels may benefit from NRIs. The long-term efficacy of NRIs for the treatment of neurogenic orthostatic hypotension-related symptoms is currently under investigation. In summary, an in-depth understanding of the pathophysiology of neurogenic orthostatic hypotension resulted in the discovery of a new therapeutic pathway targeted by NRI.
Topics: Humans; Hypotension, Orthostatic; Adrenergic Uptake Inhibitors; Norepinephrine; Atomoxetine Hydrochloride; Norepinephrine Plasma Membrane Transport Proteins; Blood Pressure
PubMed: 38766862
DOI: 10.1161/HYPERTENSIONAHA.124.22069