Reflex Control Research Articles

Brainstem Neuronal Circuitries Controlling Gastric Tonic and Phasic Contractions: A Review.

This review is on how current knowledge of brainstem control of gastric mechanical function unfolded over nearly four decades from the perspective of our research group. It describes data from a multitude of different types of studies involving retrograde neuronal tracing, microinjection of drugs, whole-cell recordings from rodent brain slices, receptive relaxation reflex, accommodation reflex, c-Fos experiments, immunohistochemical methods, electron microscopy, transgenic mice, optogenetics, and GABAergic signaling. Data obtained indicate the following: (1) nucleus tractus solitarius (NTS)-dorsal motor nucleus of the vagus (DMV) noradrenergic connection is required for reflex control of the fundus; (2) second-order nitrergic neurons in the NTS are also required for reflex control of the fundus; (3) a NTS GABAergic connection is required for reflex control of the antrum; (4) a single DMV efferent pathway is involved in brainstem control of gastric mechanical function under most experimental conditions excluding the accommodation reflex. Dual-vagal effectors controlling cholinergic and non-adrenergic and non-cholinergic (NANC) input to the stomach may be part of the circuitry of this reflex. (5) GABAergic signaling within the NTS via Sst-GABA interneurons determine the basal (resting) state of gastric tone and phasic contractions. (6) For the vagal-vagal reflex to become operational, an endogenous opioid in the NTS is released and the activity of Sst-GABA interneurons is suppressed. From the data, we suggest that the CNS has the capacity to provide region-specific control over the proximal (fundus) and distal (antrum) stomach through engaging phenotypically different efferent inputs to the DMV.

Angiotensin II-Vasopressin Interactions in The Regulation of Cardiovascular Functions. Evidence for an Impaired Hormonal Sympathetic Reflex in Hypertension and Congestive Heart Failure.

Angiotensin II (ANG II) and vasopressin (VP) interact in several physiological mechanisms, playing a role in arterial hypertension and congestive heart failure. Aim and Methods of Search: To overview the primary mechanism involved in the regulation of cardiovascular function, PubMed/Medline was searched, and authors selected original articles and reviews written in English. Angiotensin II (ANG II) and vasopressin (VP) are involved in several physiological mechanisms. ANG II stimulates VP release via angiotensin receptor 1. ANG II and VP stimulate aldosterone synthesis and secretion and enhance its action at the renal collecting duct level. VP is also involved in the cardiovascular reflex control of the sympathetic nervous system (SNS). Also, VP potentiates vasoconstriction and cardiac contractility, enhancing the effect of ANG II on sympathetic tone and arterial pressure. On the other hand, ANG II and VP act antagonistically in regulating baroreflex control of the SNS. There is evidence that high VP plasma levels increase baroreflex sympatho-inhibitory responses, and the arterial baroreflex response is shifted to lower pressure. This cardiovascular reflex control is mediated mainly in the brain, specifically in the circumventricular organ area postrema (AP). The modulation of cardiovascular reflex control induced by VP is abolished after lesions of the AP. VP modulation of baroreflex function is also under the control of α2-adrenergic pathway arising from the nucleus of the solitary tract (NTS) and synapsing on VP-ergic neurons of supraoptic and paraventricular nuclei. Presynaptic α2-adrenergic stimulation within the NTS inhibits VP release induced by hypovolemia and the effects of VP and AP on baroreflex control of SNS, thus showing baroreceptor afferent inputs are processed within the NTS and contribute to the increased baroreflex sympatho-inhibitory responses. In patients with congestive heart failure (CHF), plasma VP levels are elevated, inducing an up-regulation of aquaporin 2 water channel expression in renal collecting duct (CD) cells provoking exaggerated water retention and dilutional hyponatremia. Antagonists of VP and ANG II receptors reduce edema, body weight, and dyspnea in CHF patients. Hormonal imbalance between ANG II, VP, and SNS may induce hypertension and impaired water-electrolyte balance in cardiovascular diseases.

James Waldo Lance 1926–2019

James W. Lance was a clinical neurologist who created the first university-based department of neurology in Australia. He championed academic enquiry and the scientific basis of clinical practice, and his research had two major themes, motor control and headache. After his doctoral studies on the pyramidal tract of the cat, he became a pioneer of the new field of motor control studied in human subjects, making seminal contributions on the control of muscle tone, reflexes and movement in healthy subjects and the pathophysiology of movement disorders in patients. At the same time he developed a clinical research program into the mechanisms and management of headache, in particular migraine. These studies evolved into parallel experiments in human subjects, cats and monkeys, probing the control of the cerebral circulation and the mechanisms underlying craniofacial pain, for which he received international acclaim in both fields. He received international and Australian honours and was the first practising clinician to be elected a fellow of the Australian Academy of Science. He is rightfully credited with leading the development of academic neurology in Australia and overseas.

Location, distribution, and quantification of myenteric plexus neurons of the jejunum of quails fed with different levels of commercial Macleaya cordata extract

ABSTRACT: Coturniculture has been promising, progressing from a subsistence to a technical activity due to its quick production, low breeding investment, and rapid economic return. After the restriction of antimicrobials as growth promoters, some studies aimed to evaluate alternative products that would make the farming of healthy birds viable without impacting their performance, with commercial Macleaya cordata extract being one of these substitutes. The functions of the gastrointestinal tract are coordinated mainly by the enteric nervous system, and the myenteric plexus is responsible for the reflex control of contractile activities of the external muscles. Thus, this study located and demonstrated the distribution of the myenteric plexus, quantifing the total population of myenteric neurons (Giemsa+) and the subpopulation of myenteric nitrergic neurons (NADPH-d+), and evaluated the effects of commercial Macleaya cordata extract on these populations of quail jejunum neurons. A total of 240 one-day-old female laying quails were distributed into four treatments, with four repetitions of 15 birds each. The test groups (T1, T2, and T3) were treated with commercial Macleaya cordata extract throughout the experimental period using the following doses: T1 - test group, basal diet added with 150 ppm of the extract in the feed; T2- test group, basal diet added with100 ppm of the extract in the feed; T3 - test group, basal diet added with 50 ppm of the extract in the feed; and T4 - control group, basal diet with no added extract. The study included histological analysis, Giemsa+, and NADPH-d+ myenteric neuron staining. The results showed that the myenteric plexus is located between longitudinal layer fibers and in the transition region between the longitudinal and circular layers of the muscular tunic, with the myenteric population organized into ganglia and isolated in the region of neuronal fiber bundles. The commercial Macleaya cordata extract showed no quantitative changes in the myenteric Giemsa+ population and myenteric NADPH-d+ subpopulation, however, the groups that consumed the extract showed greater NADPH-d+ neuron activity compared to the control group, implying that the food remained longer in the intestinal lumen, therefore, enabling greater nutrient use and resulting in increased productive performance.

A Novel Neuromuscular Head-Neck Model and Its Application on Impact Analysis.

Neck muscle activation plays an important role in maintaining posture and preventing trauma injuries of the head-neck system, levels of which are primarily controlled by the neural system. Thus, the present study aims to establish and validate a neuromuscular head-neck model as well as to investigate the effects of realistic neural reflex control on head-neck behaviors during impact loading. The neuromuscular head-neck model was first established based on a musculoskeletal model by including neural reflex control of the vestibular system and proprioceptors. Then, a series of human posture control experiments was implemented and used to validate the model concerning both joint kinematics of the cervical spine and neck muscle activations. Finally, frontal impact experiments of varying loading severities were simulated with the newly established model and compared with an original model to investigate the influences of the implanted neural reflex controllers on head-neck kinematic responses. The simulation results using the present neuromuscular model showed good correlations with in-vivo experimental data while the original model even cannot reach a correct balance status. Furthermore, the vestibular reflex is noted to dominate the muscle activation in less severe impact loadings while both vestibular and proprioceptive controllers have a lot of effect in higher impact loading severity cases. In summary, a novel neuromuscular head-model was established and its application demonstrated the significance of the neural reflex control in predicting in vivo head-neck responses and preventing related injury risk due to impact loading.

Роль нейрональной NO-синтазы в реализации респираторных эффектов провоспалительного цитокина ФНО-α

In our previous studies we showed that an increase in the systemic or cerebral level of proinflammatory cytokines has a modulating effect on the reflex control of respiration. The aim of this study was to investigate the possible involvement of neuronal nitric oxide synthase (nNOS) in the hypoxic ventilatory response induced by an increased systemic level of the proinflammatory cytokine Tumor necrosis factor — α (TNF-α). To achieve this goal, we conducted experiments on urethane anesthetized rats with intravenous administration of TNF-α before and after pretreatment with 7-nitroindazole specific inhibitor of nNOS. The hypoxic ventilation response was assessed by rebreathing with a hypoxic gas mixture before and after administration of TNF-α. We found that TNF-α increased the lung ventilation in normoxia but decreased the ventilatory response to hypoxia. Pretreatment with nNOS inhibitor reduced respiratory effects of TNF-α. We believe that TNF-α can participate in the modulation of peripheral hypoxic chemoreflex not only in pathological, but also in normal physiological conditions through the activation of constitutive nNOS in the glomus cells of the carotid bodies. This makes the respiratory system urgently respond to an increase in the level of pro-inflammatory cytokines in the circulatory system. The obtained data made it possible to improve the understanding of how systemic inflammation affects the respiratory function.

Renal Transplantation Significantly Improves Autonomic Function with Normalization of Baroreflex Sensitivity as Early as Three-Month Post-transplantation.

The most common cause of mortality in chronic kidney disease patients is cardiovascular events. Cardiovascular autonomic dysfunction is likely to contribute high incidence of cardiovascular mortality, and in addition to adrenergic overdrive in these patients, there is the presence of impaired reflex control of both sympathetic and parasympathetic outflow to the heart and vasculature. Very few studies are available which show that renal transplantation (RT) improves the baroreflex function along with improvement in cardiovascular variability parameters. This prospective study was designed for the assessment of the autonomic function, i.e., heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS) in end-stage renal disease (ESRD) patients before RT and three and six months after RT and to study the effects of RT on cardiac and vascular autonomic tone and on BRS. We studied 81 ESRD patients prospectively slated for RT but only 64 patients (mean age: 33 years) completed both three and six months visits after RT for autonomic function study. Patients were evaluated in detail clinically as well as routine biochemical parameters were done on every three visits. Baroreflex function was quantified by the sequence method. Assessment of short-term HRV and BPV were done using power spectrum analysis of RR intervals and systolic BP by frequency domain analysis. The parameters of HRV after RT showed significant changes in high-frequency domain measures six months post-RT but not in low frequency. HRV in total power was also statistically significant as early as three months postrenal transplant and remained at six months. The favorable effect of RT on decreasing BPV and improving BRS is seen by as early as three months.

PENGARUH SLOW DEEP BREATHING TERHADAP TEKANAN DARAH PADA PASIEN HIPERTENSI

ABSTRAK
 Pendahuluan : Tekanan darah tinggi menjadi adalah masalah kesehatan masyarakat yang meningkat dengan signifikan. Angka kejadian hipertensi di Indonesia berjumlah 34.1% dan untuk di Jakarta 35%. Hipertensi dapat diobati dengan cara farmakologis dan non farmakologis dan juga dengan terapi alternatif. Slow deep breathing merupakan salah satu teknik latihan dan relaksasi yang membantu menjaga keadaan normal tekanan darah. Tujuan dari penelitian ini adalah untuk mengetahui pengaruh slow deep breathing pada tekanan darah di antara pasien dengan hipertensi. Metode : Design penelitian ini adalah one group pretest-posttest design. Sampel berjumlah 15 responden yang ditentukan dengan teknik purposive sampling. Analisa data dengan menggunakan t-test dependent. Latihan slow deep breathing diberikan kepada responden dua kali sehari selama satu jam selama satu minggu. Tekanan darah diukur dengan sphygmomanometer elektronik sebelum serta setelah intervensi di setiap sampel. Hasil : Latihan slow deep breathing efektif dalam mengurangi tekanan darah sistolik dan diastolik pada tingkat tersebut dengan nilai p <0,05. Diskusi : Slow deep breathing dapat menurunkan tekanan darah dengan efek melalui sistem kontrol refleks kardiovaskuler dan sensitivitas barorefleks serta penurunan tekanan darah.
 
 Kata kunci : Hipertensi, slow deep breathing, tekanan darah

Increased sympathetic and haemodynamic responses to exercise and muscle metaboreflex activation in post-menopausal women with rheumatoid arthritis.

Rheumatoid arthritis (RA) patients present exacerbated blood pressure responses to exercise, but little is known regarding the underlying mechanisms involved. This study assessed autonomic and haemodynamic responses to exercise and to the isolated activation of muscle metaboreflex in post-menopausal women with RA. Participants with RA showed augmented pressor and sympathetic responses to exercise and to the activation of muscle metaboreflex. These responses were associated with multiple pro- and anti-inflammatory cytokines and with pain. The results of the present study support the suggestion that an abnormal reflex control of circulation is an important mechanism underlying the exacerbated cardiovascular response to exercise and increased cardiovascular risk in RA. Studies have reported abnormal cardiovascular responses to exercise in rheumatoid arthritis (RA) patients, but little is known regarding the underlying mechanisms involved. This study assessed haemodynamic and sympathetic responses to exercise and to the isolated activation of muscle metaboreflex in women diagnosed with RA. Thirty-three post-menopausal women diagnosed with RA and 10 matched controls (CON) participated in this study. Mean arterial pressure (MAP), heart rate (HR) and muscle sympathetic nerve activity (MSNA frequency and incidence) were measured during a protocol of isometric knee extension exercise (3min, 30% of maximal voluntary contraction), followed by post-exercise ischaemia (PEI). Participants with RA showed greater increases in MAP and MSNA during exercise and PEI than CON (ΔMAPexercise =16±11 vs. 9±6mmHg, P=0.03; ΔMAPPEI =15±10 vs. 5±5mmHg, P=0.001; ΔMSNAexercise =17±14 vs. 7±9burstsmin-1 , P=0.04; ΔMSNAPEI =14±10 vs. 6±4burstsmin-1 , P=0.04). Autonomic responses to exercise showed significant (P<0.05) association with pro- (i.e. IFN-γ, IL-8, MCP-1 and TNFα) and anti-inflammatory (i.e. IL-1ra and IL-10) cytokines and with pain. In conclusion, post-menopausal women with RA showed augmented pressor and sympathetic responses to exercise and to the activation of muscle metaboreflex. These findings provide mechanistic insights that may explain the abnormal cardiovascular responses to exercise in RA.

Thermoregulatory reflex control of cutaneous vasodilation in healthy aging

ABSTRACT Reflex cutaneous vasodilation during heating is attenuated in healthy human aging secondary to blunted increases in efferent skin sympathetic nervous system activity (SSNA) and reductions in end-organ sensitivity. Whether age-related alterations in the mean body temperature ( b) threshold for increasing SSNA and/or the sensitivity of responses are evident with aging have not been examined. We tested the hypotheses that the Tb threshold for SSNA and cutaneous vascular conductance (CVC) would be increased, but the sensitivity would be reduced, with aging. Reflex vasodilation was induced in 13 young (23 ± 3 y) and 13 older (67 ± 7 y) adults using a water-perfused suit to systematically increase mean skin and esophageal temperatures. SSNA (peroneal microneurography) and red cell flux (laser Doppler flowmetry) in the innervated dermatome were continuously measured. SSNA was normalized to baseline; CVC was normalized as a percentage of maximal CVC. Baseline b was lower in older adults (36.0 ± 0.4°C vs 36.4 ± 0.3°C; p = 0.005). During passive heating, the ∆ b thresholds for increasing SSNA and CVC were greater (1.3 ± 0.4°C vs 0.9 ± 0.3°C; p = 0.007 and 1.3 ± 0.4°C vs 0.8 ± 0.3°C; p = 0.002, respectively) in older adults. The slope of the relation between both SSNA (0.31 ± 0.23 vs 0.13 ± 0.10 V⋅s⋅°C −1; p = 0.01) and CVC (87.5 ± 50.1 vs 32.4 ± 18.1%max⋅°C−1; p = 0.002) vs b was lower in older adults. The relative b threshold for activation of SSNA and the initiation of reflex cutaneous vasodilation is higher in older adults, and once activated, the sensitivity of both responses is diminished, supporting the concept that the efferent component of the thermoregulatory reflex arc is impaired in healthy aging. Abbreviations: CI: confidence interval; CVC: cutaneous vascular conductance; SSNA: skin sympathetic nervous system activity; b: mean body temperature; Tes: esophageal temperature; sk: mean skin temperature.

Mechanisms Underlying Neuroplasticity in the Nucleus Tractus Solitarii Following Hindlimb Unloading in Rats

Hindlimb unloading (HU) in rats induces cardiovascular deconditioning (CVD) analogous to that observed in individuals exposed to microgravity or bed rest. Among other physiological changes, HU rats exhibit autonomic imbalance and altered baroreflex function. Lack of change in visceral afferent activity that projects to the brainstem in HU rats suggests that neuronal plasticity within central nuclei processing cardiovascular afferents may be responsible for these changes in CVD and HU. The nucleus tractus solitarii (nTS) is a critical brainstem region for autonomic control and integration of cardiovascular reflexes. In this study, we used patch electrophysiology, live-cell calcium imaging and molecular methods to investigate the effects of HU on glutamatergic synaptic transmission and intrinsic properties of nTS neurons. HU increased the amplitude of monosynaptic excitatory postsynaptic currents and presynaptic calcium entry evoked by afferent tractus solitarii stimulus (TS-EPSC); spontaneous (s) EPSCs were unaffected. The addition of a NMDA receptor antagonist (AP5) reduced TS-EPSC amplitude and sEPSC frequency in HU but not control. Despite the increase in glutamatergic inputs, HU neurons were more hyperpolarized and exhibited intrinsic decreased excitability compared to controls. After block of ionotropic glutamatergic and GABAergic synaptic transmission (NBQX, AP5, Gabazine), HU neuronal membrane potential depolarized and neuronal excitability was comparable to controls. These data demonstrate that HU increases presynaptic release and TS-EPSC amplitude, which includes a NMDA receptor component. Furthermore, the decreased excitability and hyperpolarized membrane after HU are associated with enhanced GABAergic modulation. This functional neuroplasticity in the nTS may underly the CVD induced by HU.

Role of Neuroendocrine, Immune, and Autonomic Nervous System in Anorexia Nervosa-Linked Cardiovascular Diseases.

Anorexia nervosa represents a severe mental disorder associated with food avoidance and malnutrition. In patients suffering from anorexia nervosa, cardiovascular complications are the main reason leading to morbidity and mortality. However, the origin and pathological mechanisms leading to higher cardiovascular risk in anorexia nervosa are still unclear. In this aspect, the issue of exact pathological mechanisms as well as sensitive biomarkers for detection of anorexia nervosa-linked cardiovascular risk are discussed. Therefore, this review synthesised recent evidence of dysfunction in multiple neuroendocrine axes and alterations in the immune system that may represent anorexia nervosa-linked pathological mechanisms contributing to complex cardiovascular dysregulation. Further, this review is focused on identification of non-invasive biomarkers for the assessment of increased cardiovascular risk in anorexia nervosa that can be linked to a clinical application. Complex non-invasive assessment of cardiovascular autonomic regulation—cardiac vagal control (heart rate variability), sympathetic vascular activity (blood pressure variability), and cardiovascular reflex control (baroreflex sensitivity)—could represent a promising tool for early diagnosis, personalized therapy, and monitoring of therapeutic interventions in anorexia nervosa particularly at a vulnerable adolescent age.

Skin tattooing impairs sweating during passive whole body heating.

Tattooing of the skin involves repeated needle insertions to deposit ink into the dermal layer of the skin, potentially damaging eccrine sweat glands and the cutaneous vasculature. This study tested the hypothesis that reflex increases in sweat rate (SR) and cutaneous vasodilation are blunted in tattooed skin (TAT) compared with adjacent healthy skin (CON) during a passive whole body heat stress (WBH). Ten individuals (5 males and 5 females) with a sufficient area of tattooed skin participated in the study. Intestinal temperature (Tint), skin temperature (Tskin), skin blood flow (laser Doppler flux; LDF), and SR were continuously measured during normothermic baseline (34°C water perfusing a tube-lined suit) and WBH (increased Tint 1.0°C via 48°C water perfusing suit). SR throughout WBH was lower for TAT compared with CON (P = 0.033). Accumulated sweating responses during WBH (area under curve) were attenuated in TAT relative to CON (23.1 ± 12.9, 26.9 ± 14.5 mg/cm2, P = 0.043). Sweating threshold, expressed as the onset of sweating in time or Tint from the initiation of WBH, was not different between TAT and CON. Tattooing impeded the ability to obtain LDF measurements. These data suggest that tattooing functionally damages secretion mechanisms, affecting the reflex capacity of the gland to produce sweat, but does not appear to affect neural signaling to initiate sweating. Decreased sweating could impact heat dissipation especially when tattooing covers a higher percentage of body surface area and could be considered a potential long-term clinical side effect of tattooing.NEW & NOTEWORTHY This study is the first to assess the reflex control of sweating in tattooed skin. The novel findings are twofold. First, attenuated increases in sweat rate were observed in tattooed skin compared with adjacent healthy non-tattooed skin in response to a moderate increase (1.0°C) in internal temperature during a passive whole body heat stress. Second, reduced sweating in tattooed skin is likely related to functional damage to the secretory mechanisms of eccrine sweat glands, rendering it less responsive to cholinergic stimulation.

The Legal Framework for Psychological Operations and Influence Operations Under International Law, the Law Applicable to Armed Conflict and International Criminal Law

Psychological warfare represents an intriguing topic at the crossroads between politics, security, sociology and psychology. Literature about processes known as “reflex control”, “mind games” or “mind wars” makes the topic even more intriguing. If possible, additional reasons to deepen the implications of psychological operations may derive from possible enhancements due to advanced neuroscience and eventually enhanced capabilities to decode intention and prediction crime and more generally reactions . Advanced brain scanning techniques will not be confined to security checks or interrogations operations and will likely be applied to a wide range of situations to include negotiations and situations in which the assessment of responses to conveyed messages is crucial. Further, the current architecture of information may enhance the effects for massive influence and information operations: what is often labelled as the “age of information”, due to the illusion of real time unlimited open access to information through the web, is rather characterized by widespread lack of media education, volatility of interest in security and international politics by the average news addresses, dramatic drop in information demand. Psychological operations (PSYOPS) have been considered within the wider context of political warfare and propaganda whereas it has been observed that even the very concept of “deterrence” is an essentially psychological phenomenon rather than a simple reflection of quantity and quality of military forces . As psychological warfare is not practiced solely by States and the psychological impact and dimension of any criminal act is nowadays carefully assessed by terrorist organizations and other criminal organizations. Target may accordingly be chosen in order to maximize an emotional political effect which may go further and beyond the primary effect of spreading terror. Such secondary effects or reflexes may, as we are currently witnessing, include the attempt to induce political shifts in the electorate for example from moderate attitudes towards the draw of xenophobia, realizing third degree effects like the radicalization within categories affected by the shift. Accordingly, the Paper addresses the issue of the prohibition of warmongering and hatred propaganda with the intention to outline and map eventual further legal constrains based upon pretences by States to exercise information sovereignty, as juxtaposed the right to access information. Human rights concerns as those related with freedom of speech and further concerns emerging from the right to ancestry and cognitive self-determination and freedom of thought are dealt in a separate part. The Paper further addresses psyops under LOAC and ICL.

Design of Muscle Reflex Control for Upright Standing Push-Recovery Based on a Series Elastic Robot Ankle Joint.

In physical human–robot interaction environment, ankle joint muscle reflex control remains significant and promising in human bipedal stance. The reflex control mechanism contains rich information of human joint dynamic behavior, which is valuable in the application of real-time decoding motion intention. Thus, investigating the human muscle reflex mechanism is not only meaningful in human physiology study but also useful for the robotic system design in the field of human–robot physical interaction. In this paper, a specialized ankle joint muscle reflex control algorithm for human upright standing push-recovery is proposed. The proposed control algorithm is composed of a proportional-derivative (PD)-like controller and a positive force controller, which are employed to mimic the human muscle stretch reflex and muscle tendon force reflex, respectively. Reflex gains are regulated by muscle activation levels of contralateral ankle muscles. The proposed method was implemented on a self-designed series elastic robot ankle joint (SERAJ), where the series elastic actuator (SEA) has the potential to mimic human muscle–tendon unit (MTU). During the push-recovery experimental study, the surface electromyography (sEMG), ankle torque, body sway angle, and velocity of each subject were recorded in the case where the SERAJ was unilaterally kneed on each subject. The experimental results indicate that the proposed muscle reflex control method can easily realize upright standing push-recovery behavior, which is analogous to the original human behavior.

Mechanisms underlining excitatory synaptic plasticity in the Nucleus Tractus Solitarii following Cardiovascular Deconditioning

The nucleus tractus solitarii (nTS) is a critical central region for autonomic control and integration of cardiovascular reflexes. Neuroplasticity in nTS contributes to several cardiovascular dysfunctions. Our previous data showed that Hindlimb‐unloading (HU), a well‐established model of cardiovascular deconditioning in rats, increases glutamatergic neurotransmission yet reduces the excitability of nTS neurons. In this study we aimed to investigate the mechanisms underlining these alterations. For this purpose, stainless wire rings were placed in the tail of male Sprague‐Dawley rats (3 weeks). After one week of recovery the rings was connected to a suspension apparatus and rats were suspended at an angle of 30–35° for two weeks with free access to food and water. Control animals were maintained in normal postural conditions. After the HU protocol, coronal brainstem slices were generated and the whole‐cell patch clamp technique was performed to evaluate the synaptic neurotransmission and electrophysiological properties of nTS neurons. Compared to control rats, HU increased the amplitude of excitatory postsynaptic currents evoked by afferent tractus solitarii stimulus (TS‐EPSC). The addition of a NMDA receptor antagonist (AP5, 10 μM) significantly reduced TS‐EPSC amplitude in HU but not controls. Despite the increase in glutamatergic inputs, the neurons of HU vs control rats are hyperpolarized and have decreased excitability. The block of both NMDA and non‐NMDA (NBQX, 10 μM) glutamatergic receptors did not affect these parameters. However, in the presence of a GABAA receptor antagonist (Gabazine, 25 μM) the resting membrane potential depolarized and excitability of HU neurons were comparable to neurons from control rats. The results indicate that HU increases TS‐EPSC amplitude via a NMDA receptor component. Furthermore, the decreased excitability and hyperpolarized membrane is associated with enhanced GABAergic modulation to these neurons. This functional neuroplasticity in the nTS may contribute to the cardiovascular deconditioning induced by HU.Support or Funding InformationHL132836 AAS lundbeck fellowship

Obesity‐Induced Sympathoexcitation is Associated with Glial Senescence in the Brainstem

Previous studies from our laboratory showed that high fat diet‐induced obesity causes cellular senescence in the key brainstem region, the rostral ventrolateral medulla which is critical for the tonic and reflex control of sympathetic nervous system. Cellular senescence is characterized by a state of irreversible growth arrest and senescence‐associated secretory phenotype (SASP) in proliferating cells. In the current study, we wanted to investigate which cell type undergoes senescence in the brainstem in obesity. Neurons are post‐mitotic and do not undergo senescence, whereas glial cells can undergo senescence. Hence we hypothesized that obesity induces glial senescence in the brainstem. To address this hypothesis, 2‐month old C57BL/6J mice were fed with high fat diet (60% fat; n=5) and chow diet (10% fat; n=5) for 16 weeks. The animals were sacrificed at the end of the experiment, and their brains were collected for further processing. The freshly isolated brainstem was enzymatically digested (45 minutes, 37°C) and filtered through a 30μm mesh to form a cell suspension. Neuron isolation kit from Miltenyi Biotec was used to isolate glial and neuronal enriched cell population from the brainstem. RNA was extracted from these sorted cells and used for RT‐PCR analysis. Senescence was assessed using gene expression of cell cycle inhibitors and SASP factors. Data was analyzed by unpaired student’s t‐test and a p‐value less than 0.05 was considered statistically significant. We observed an increase in the gene expression of cell cycle inhibitors, p21 and p53 in the glial cell fraction isolated from the brainstem of obese mice compared to its lean counterparts. In addition, there was an increase in the mRNA levels of SASP factors such as the IL‐6 and MCP1 suggesting that obesity induces glial senescence in the brainstem. We were not able to obtain viable neurons for senescence analysis. Glial cells are known to play a supporting role in neuronal function through regulation of neurotransmission. Future studies will address glial cell specific mechanisms and understand how glia‐neuron crosstalk contributes to sympathetic nerve overactivity in obesity.Support or Funding InformationNIH‐HL148844 and RED account funds

Modulation of Cough Reflex by Gaba-Ergic Inhibition in Medullary Raphé of the Cat.

We studied the effects of GABA receptor agonists microinjections in medullary raphé on the mechanically induced tracheobronchial cough response in anesthetized, unparalyzed, spontaneously breathing cats. The results suggest that GABA-ergic inhibition significantly contributes to the regulation of cough reflex by action of both GABA(A) and GABA(B) receptors. The data are consistent with inhomogeneous occurrence of GABA-ergic neurons in medullary raphé and their different involvement in the cough reflex control. Cells within rostral nucleus raphéobscurus with dominant role of GABA(A) receptors and neurons of rostral nucleus raphépallidus and caudal nucleus raphémagnus with dominant role of GABA(B) receptors participate in regulation of cough expiratory efforts. These cough control elements are distinct from cough gating mechanism. GABA-ergic inhibition in the raphé caudal to obex had insignificant effect on cough. Contradictory findings for GABA, muscimol and baclofen administration in medullary raphé suggest involvement of coordinated activity of GABA on multiple receptors affecting raphé neurons and/or the local neuronal circuits in the raphé modulating cough motor drive.

Bio-inspired neuromuscular reflex based hopping controller for a segmented robotic leg

It has been shown that human-like hopping can be achieved by muscle reflex control in neuromechanical simulations. However, it is unclear if this concept is applicable and feasible for controlling a real robot. This paper presents a low-cost two-segmented robotic leg design and demonstrates the feasibility and the benefits of the bio-inspired neuromuscular reflex based control for hopping. Simulation models were developed to describe the dynamics of the real robot. Different neuromuscular reflex pathways were investigated with the simulation models. We found that stable hopping can be achieved with both positive muscle force and length feedback, and the hopping height can be controlled by modulating the muscle force feedback gains with the return maps. The force feedback neuromuscular reflex based controller is robust against body mass and ground impedance changes. Finally, we implemented the controller on the real robot to prove the feasibility of the proposed neuromuscular reflex based control idea. This paper demonstrates the neuromuscular reflex based control approach is feasible to implement and capable of achieving stable and robust hopping in a real robot. It provides a promising direction of controlling the legged robot to achieve robust dynamic motion in the future.

Central nervous system control of micturition reflex

Central nervous system control of micturition reflex