Stretch Receptors Research Articles

Learning to Breathe: Cholinergic modulation of plasticity associated with the gating of pulmonary stretch receptor input in the nucleus of the solitary tract.

The lateral subnucleus of nucleus of the solitary tract (l‐NTS) is a primary synaptic site of visceral afferents, including pulmonary stretch receptors (PSRs). The PSR‐mediated inspiratory off‐switch (IOS), which is a component of the Hering‐Breuer reflex is a major determinant of the sensory modulation of breathing. Previously, we demonstrated that rhythmic vagal stimulation or lung inflations entrain phrenic nerve activity. Repetitive vagal stimulation or lung inflation induces a progressive shift from sensory (PSR) to anticipatory (learned) centrally mediated IOS (Dutschmann et al., 2009). In the present study, we investigated whether cholingeric neurotransmission within l‐NTS modulates PSR associated plasticity.Juvenile Sprague‐Dawley rats of either gender weighing 40–80 g (P21–28) were used in the decerebrated arterially‐perfused in situ preparations to record the phrenic nerve activity (PNA). The Hering‐Breuer reflex was evoked by inflating the lungs (1–2 mL tidal volume) at 40 inflations min−1 for 2 min. Lung inflation trials were repeated 10 times, at For the experimental groups, either atropine (ATR, muscarinic antagonist, 5 mM) or mecamylamine (MEC, nicotinic antagonist, 5 mM) were microinjected bilaterally in the l‐NTS after one lung inflation trial. Following a 3‐min interval, the lung inflation trials were repeated 10 times with a 3‐min recovery‐period between each trial. The control group received only 10 lung inflation trials. The 1st, 3rd, 5th and 7th trials were analyzed.The injection of atropine, a muscarinic receptor antagonist, in the l‐NTS promoted the plasticity switching the IOS from being initiated only by sensory activation to being initiated centrally, before the sensory input. In contrast, the nicotinic antagonist mecamylamine prevented the shift from sensory to central of IOS. In conclusion, we suggest that the muscarinic and nicotinic receptors in the l‐NTS have opposite roles in modulating the Hering‐Breuer‐induced plasticity that affects the IOS.Support or Funding InformationThe study was funded by the Australian Research Council and a fellowship for WF from FAPESP, Brazil.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

New insights into a decerebrate feline model of swallow‐breathing coordination

In the medulla, the swallow and respiratory central pattern generators (CPGs) interact to coordinate swallow initiation and permit swallow execution during the expiratory phase of breathing. Disruption of swallow‐breathing coordination can result in dysphagia, which is a major cause of morbidity and mortality in many neuro‐muscular diseases, especially stroke. Despite extensive study, the precise mechanisms of swallow‐breathing coordination are not known. We tested the hypothesis that both central inspiratory activity and vagal feedback from the lungs are key elements for effective swallow‐breathing coordination. Swallows were triggered by electrical stimulation of the superior laryngeal nerves (SLN) or by injection of water into the pharyngeal cavity in decerebrate, paralyzed and artificially ventilated cats while motor activities were recorded from phrenic, hypoglossal, lumbar and vagal nerves. Mechanical ventilation was either triggered by central inspiratory activity or set independently from the phrenic activity to alter the timing of bronchopulmonary vagal afferent input and allow analysis of its influence on swallow‐breathing coordination. We observed two types of swallows that produced opposite effects on central respiratory‐rhythm resetting across all conditions: post‐Inspiratory type swallows disrupted central I activity without affecting expiration, whereas expiratory type swallows prolonged expiration without affecting central inspiratory activity. Repetitive swallows observed during apnea reset the E2 phase of central respiration and produced facilitation of swallow motor output. Moreover, swallow initiation was negatively modulated by vagal feedback and was reset by lung inflation. Collectively, these findings support a reciprocal inhibition between central inspiration and the swallow CPG and they are consistent with a role for pulmonary stretch receptors in the coordination between brainstem CPGs for breathing and swallowing. They may also prove relevant for healthcare management of dysphagia.Support or Funding InformationOT2OD023854‐01, HL109025This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Structure of vagal afferent nerve terminal fibers in the mouse trachea

The structure of primary afferent nerve terminals profoundly influences their function. While the complex vagal airway nerve terminals (stretch receptors, cough receptors and neuroepithelial bodies) were thoroughly characterized, much less is known about the structure of airway nerves that do not form distinct complex terminals (often termed free nerve fibers). We selectively induced expression of GFP in vagal afferent nerves in the mouse by transfection with AAV-GFP virus vector and visualized nerve terminals in the trachea by whole organ confocal imaging. Based on structural characteristics we identified four types of vagal afferent nerve fiber terminals in the trachea. Importantly, we found that distinct compartments of tracheal tissue are innervated by distinct nerve fiber terminal types in a non-overlapping manner. Thus, separate terminal types innervate tracheal epithelium vs. anterolateral tracheal wall containing cartilaginous rings and ligaments vs. dorsal wall containing smooth muscle. Our results will aid the study of structure-function relationships in vagal airway afferent nerves and regulation of respiratory reflexes.

Urinary Retention after Orthopedic Surgery: Identification of Risk Factors and Management

Urinary retention is a common complication of post-surgery and anaesthesia and is commonly known as Post-operative Urinary Retention (POUR). The risk of retention is especially high following anorectal surgery, hernia repair, and orthopedic surgery and increases with advancing age of the patient. Many factors are thought to contribute to the development of POUR including traumatic catheterization, pre-existing urologic pathology, and increased fluid requirements of surgery combined with the use of analgesics, opiates and components of anaesthesia The regular capacity of the bladder ranges between 400-600 cc, with the first signal of micturition occurring when the bladder capacity is at 150 cc to the feeling of fullness when to capacity reaches 300 cc. The sensation of fullness occurs at a certain level of afferent activity. Once the voluntary signal to begin voiding has been issued, neurons in pontine micturition centre fire maximally causing the wall of the bladder to contract via the stretch receptors in the bladder. Consequently, the parasympathetic neurons are activated leading to the contraction of the detrusor muscle and relaxation of the bladder neck resulting in micturition. Hindrance to these pathways can accelerate the likelihood of developing POUR. Conservative measure are needed to assist the patient to pass urine, else the bladder will need to be drained using either an intermittent catheter or an indwelling urethral catheter. While there exists little information concerning the outcome of retrospective studies on POUR, this particular review sheds new light on the management strategies and risk factors for the development of POUR after orthopedic surgery to prevent the long-term consequences of this complication.

A ligamentous explanation for overactive bladder symptoms as defined by International Continence Society in the female.

The International Continence Society (ICS) committee has defined overactive bladder (OAB) as “a syndrome characterized by symptoms of urgency, with or without urgency incontinence, usually with increased daytime frequency and nocturia (increased night time urination). The term OAB can only be used if there is no proven infection or other obvious pathology”. Though the ICS gives no anatomical basis for OAB, it is suggested that the cause is from the detrusor itself. In this review, urodynamic evidence is presented that OAB in the female may be a prematurely activated but normal micturition reflex, as predicted by the Integral Theory. Anatomically, a trampoline analogy explains how loose ligaments prevent the vaginal stretching so important for support of the bladder base stretch receptors which control the reflex. Surgical cure of OAB by repair of loose cardinal/ uterosacral ligaments are an important proof that the origins of OAB are outside the bladder, laxity of the suspensory ligaments which in turn, inactivate the striated muscle vector forces which contract against them. This concept is not in in conflict with the definitions of the ICS. Rather it provides a causative anatomical background to the definitions.

Muscle Spindle and Comparison of Fish Muscle Spindle with Other Vertebrates

The aim of this study is to bring together the literature knowledge on muscule spindels that has been made up to until now and compare fish muscule spindels with other vertebrates. Muscle spindles are stretch receptor of skeletal muscles which detect the rate and degree of muscle length. According to the available literature, this review is considered as a one in making a comparison of fish muscle spindle and other vertebrates. Fish muscle spindle possesses single intrafusal muscle fiber similar to snake and lizard muscle spindle and have a double capsule similar in all vertebrates have studied. No significant differences in the length and diameter of intrafusal muscle fibers by comparison of muscle size. In fish and other vertebrates muscle spindles are supplied with one sensory ending (exception in mammalian may, in addition, be supplied with one or more secondary sensory endings) and receive its motor innervation from branches of axons that also innervate extrafusal muscle fibers. No investigation has been done about motor innervation of fish muscle spindle.

The arteriolar injury in hypertension

In 1937, Drs. Moritz and Oldt described arteriolar injuries in the kidneys (and other viscera) in hypertension, across the age range, in both sexes, and, in different races. This hypothesis proposes that injuries to vasomotor nerves cause the arteriolar injury in the kidney in hypertension, (as well as that in the uterus in preeclampsia). Different patterns of perivascular hyalinisation in different viscera are clues to the varying causes and consequences of arteriolar injury. In the uterus there is a symmetrical, perivascular “halo of hyalinisation” that marks the lines of extension of regenerating, injured nerves to the placental bed, whereas in the kidney there is a disordered and asymmetrical “halo of hyalinisation” where persistent, and recurrent, increases in intravascular pressures interrupt development of regenerating nerves. Consequences of injuries to vasomotor nerves include releasing a “soup” of cytokines that cause regeneration of “new” nerves expressing primitive, pain and stretch receptors including TRPV-1 and P2X3 purinergic “stretch” receptors that may be significant in the afferent mechanism in preeclampsia. There is also concurrent, “background” hyperplasia of denervated tunica media and intima leading to narrowing of the arterioles and a further drive to hypertension through renal ischaemia (Goldblatt, 1942). These observations require support from animal studies and other investigations to establish causation. This hypothesis may provide a number of potential mechanisms that reinforce, or accelerate, the physiological processes that contribute to hypertension.

Ca2+ mediates axotomy-induced necrosis and apoptosis of satellite glial cells remote from the transection site in the isolated crayfish mechanoreceptor

Severe nerve injury such as axotomy induces neuron degeneration and death of surrounding glial cells. Using a crayfish stretch receptor that consists of a single mechanoreceptor neuron enveloped by satellite glia, we showed that axotomy not only mechanically injures glial cells at the transection location, but also induces necrosis or apoptosis of satellite glial cells remote from the transection site. We studied Ca2+role in spontaneous or axotomy-induced death of remote glial cells. Stretch receptors were isolated using the original technique that kept the neuron connected to the ventral cord ganglion (control preparations). Using Ca2+-sensitive fluorescence probe fluo-4, we showed Ca2+ accumulation in neuronal perikarion and glial envelope. Ca2+ gradually accumulated in glial cells after axotomy. In saline with triple Ca2+ concentration the axotomy-induced apoptosis of glial cells increased, but spontaneous or axotomy-induced necrosis was unexpectedly reduced. Saline with 1/3[Ca2+], oppositely, enhanced glial necrosis. Application of ionomycin, CdCl2, thapsigargin, and ryanodine showed the involvement of Ca2+ influx through ionic channels in the plasma membrane, inhibition of endoplasmic reticulum Ca2+-ATPase, and Ca2+ release from endoplasmic reticulum through ryanodine receptors in axotomy-induced glial necrosis. Apoptosis of glial cells surrounding axotomized neurons was promoted by ionomycin and thapsigargin. Possibly, other Ca2+ sources such as penetration through the plasma membrane contributed to axotomy-induced apoptosis and necrosis of remote glial cells. Thus, modulating different pathways that maintain calcium homeostasis, one can modulate axotomy-induced death of glial cells remote from the transection site.

Gastrointestinal Involvement in Systemic Sclerosis: An Update.

Gastrointestinal Involvement in Systemic Sclerosis: An Update.

Aerosol furosemide for dyspnea: Controlled delivery does not improve effectiveness

Aerosolized furosemide has been shown to relieve dyspnea; nevertheless, all published studies have shown great variability in response. This dyspnea relief is thought to result from the stimulation of slowly adapting pulmonary stretch receptors simulating larger tidal volume. We hypothesized that better control over aerosol administration would produce more consistent dyspnea relief; we used a clinical ventilator to control inspiratory flow and tidal volume. Twelve healthy volunteers inhaled furosemide (40mg) or placebo in a double blind, randomized, crossover study. Breathing Discomfort was induced by hypercapnia during constrained ventilation before and after treatment. Both treatments reduced breathing discomfort by 20% full scale. Effectiveness of aerosol furosemide treatment was weakly correlated with larger tidal volume. Response to inhaled furosemide was inversely correlated to furosemide blood level, suggesting that variation among subjects in the fate of deposited drug may determine effectiveness. We conclude that control of aerosol delivery conditions does not improve consistency of treatment effect; we cannot, however, rule out placebo effect.

Relationship between endothelin-1 and p38 MAPK and PI3K/Akt signaling pathways during mechanical stretch-induced enhancement of adhesion of rat pulmonary microvascular endothelial cells

Objective To evaluate the relationship between endothelin-1 (ET-1) and p38 mitogen-activated protein kinase (p38 MAPK) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathways during mechanical stretch-induced enhancement of adhesion of rat pulmonary microvascular endothelial cells (PMVECs). Methods Rat PMVECs were seeded in the culture plate at a density of 0.5×105 cells/ml (2 ml/well) and divided into 5 groups (n=24 each) using a random number table: control group (group C), mechanical stretch group (group MS), mechanical stretch plus specific PI3K inhibitor LY294002 group (LY group), mechanical stretch plus specific p38 MAPK inhibitor SB203580 group (SB group), and mechanical stretch plus selective ETA receptor blocker BQ123 group (BQ group). Cells were exposed to 20% cyclic stretch at 0.3 Hz for 4 h using a sine wave.In LY, SB and BQ groups, LY294002, SB203580 and BQ123 at the final concentration of 10 μmol/L were added, respectively, after mechanical stretch, cells were incubated for 10 min, and then extracted and purified rat polymorphonuclear neutrophil leukocytes (PMNs, 5×105 cells/well) were added and co-incubated with PMVECs for 30 min and then washed out.The concentrations of ET-1 and interleukin-6 (IL-6) in the culture medium were determined using enzyme-linked immunosorbent assay.The expression of phosphorylated p38 MAPK (p-p38 MAPK) and phosphorylated Akt (p-Akt) was detected by Western blot.Adhesion of PMNs was measured by immuno-histochemistry, and the adhesion rate was calculated.The expression of P-selectin mRNA was detected using real-time polymerase chain reaction. Results Compared with group C, the concentrations of IL-6 and ET-1 in the culture medium were significantly increased, the expression of p-p38 MAPK, p-Akt and P-selectin mRNA was up-regulated, and the adhesion rate of PMNs was increased in the other four groups (P<0.05). Compared with group MS, the concentration of IL-6 in the culture medium was significantly decreased, the expression of p-Akt and P-selectin mRNA was down-regulated, and the adhesion rate of PMNs was decreased in LY, SB and BQ groups, the concentration of ET-1 in the culture medium was significantly decreased in group BQ, and the expression of p-p38 MAPK was significantly down-regulated in SB and BQ groups (P<0.05). Conclusion The signaling mechanism underlying ET-1-mediated enhancement of rat PMVEC adhesion may be related to activating p38 MAPK and PI3K/Akt signaling pathways. Key words: Endothelin-1; p38 Mitogen-activated protein kinases; 1-Phosphatidylinositol 3-kinase; Protein-serine-threonine kinases; Lung; Endothelial cells; Cell adhesion

Involvement of MAPK, Akt/GSK-3β and AMPK/mTOR signaling pathways in protection of remote glial cells from axotomy-induced necrosis and apoptosis in the isolated crayfish stretch receptor.

Severe mechanical nerve injury such as axotomy can lead to neuron degeneration and death of surrounding glial cells. We showed that axotomy not only mechanically injures glial cells at the cutting location, but also induces necrosis or apoptosis of satellite glial cells remote from the transection site. Therefore, axon integrity is necessary for survival of surrounding glial cells. We used the crayfish stretch receptor that consists of a single mechanoreceptor neuron enveloped by satellite glial cells as a simple, but informative model object in the study of the role of various signaling proteins in axotomy-induced death of remote glial cells. After axon transection, stretch receptors were isolated and incubated in saline in the presence or without specific inhibitors of various signaling proteins. Inhibition of MEK1/2, p38, Akt, GSK-3β and mTOR increased axotomy-induced apoptosis of remote glial cells, whereas inhibition of ERK1/2 and GSK-3β enhanced necrosis. This suggests the involvement of these signaling proteins in protective, antiapoptotic and antinecrotic processes in the remote satellite glia surrounding the axotomized mechanoreceptor neuron.

Fast calcium transients translate the distribution and conduction of neural activity in different regions of a single sensory neuron.

In the present study, cytosolic calcium concentration changes were recorded in response to various forms of excitations, using the fluorescent calcium indicator dye OG-BAPTA1 together with the current or voltage clamp methods in stretch receptor neurons of crayfish. A single action potential evoked a rise in the resting calcium level in the axon and axonal hillock, whereas an impulse train or a large saturating current injection would be required to evoke an equivalent response in the dendrite region. Under voltage clamp conditions, amplitude differences between axon and dendrite responses vanished completely. The fast activation time and the modulation of the response by extracellular calcium concentration changes indicated that the evoked calcium transients might be mediated by calcium entry into the cytosol through a voltage-gated calcium channel. The decay of the responses was slow and sensitive to extracellular sodium and calcium concentrations as well as exposure to 1-10mM NiCl2 and 10-500µM lanthanum. Thus, a sodium calcium exchanger and a calcium ATPase might be responsible for calcium extrusion from the cytosol. Present results indicate that the calcium indicator OG-BAPTA1 might be an efficient but indirect way of monitoring regional membrane potential differences in a single neuron.

Afidopyropen: New and potent modulator of insect transient receptor potential channels

The commercial insecticides pymetrozine and pyrifluquinazon control plant-sucking pests by disturbing their coordination and ability to feed. We have previously shown that these compounds act by overstimulating and eventually silencing vanilloid-type transient receptor potential (TRPV) channels, which consist of two proteins, Nanchung and Inactive, that are co-expressed exclusively in insect chordotonal stretch receptor neurons. Here we show that a new insecticidal compound, afidopyropen, modulates chordotonal organs of American grasshoppers (Schistocerca americana) in the same fashion. Afidopyropen stimulated heterologously expressed TRPV channels from two different insect species - fruit fly (Drosophila melanogaster) and pea aphid (Acyrthosiphon pisum) - but did not affect function of the mammalian TRPV channel TRPV4. Activation of the insect TRPVs required simultaneous expression of both Nanchung and Inactive proteins. Tritium-labeled afidopyropen bound fruit fly TRPVs with higher affinity than pymetrozine and competed with pymetrozine for binding. Nanchung protein formed the main binding interface for afidopyropen, whereas co-expression of Inactive dramatically increased binding affinity. Another modulator of chordotonal organs, flonicamid, did not activate insect TRPV channels, nor did it compete with afidopyropen for binding, indicating that it has a different target site. These results define afidopyropen as a new, potent and specific modulator of insect TRPV channels, and provide insight into the unique binding mode of these compounds.

Loss of thrombospondin reveals a possible role for the extracellular matrix in chordotonal cap cell elongation

In the Drosophila larva, major proprioceptive input is provided to the brain by sub-epidermal stretch receptors called chordotonal organs (ChO). Similarly to the body wall muscle that needs to be attached on both of its sides to the larval exoskeleton in order to generate movement, the sensory unit of a ChO must be stably anchored to the cuticle on both of its sides in order to sense the relative displacement of body parts. Through an RNAi screen we have identified thrombospondin (Tsp), a secreted calcium binding glycoprotein, as a critical component in the anchoring of ChOs to the cuticle. We show that the Tsp protein starts to accumulate in the extracellular matrix (ECM) surrounding the ChO attachment cells towards the end of embryogenesis and that it becomes highly concentrated at the attachment junction during larval stages. In the absence of Tsp, the ChO's accessory cells fail to form a stable junction with their epidermal attachment cells and organ integrity is not maintained. Tsp is a known player in the establishment of the myotendinous junctions in both invertebrates and vertebrates. Thus, our findings extend the known similarities between muscle-attachment and ChO-attachment cells. In addition to its role in establishing the ChO attachment junctions, Tsp was found to affect ligament cell migration and cap cell elongation. Most interestingly, the Tsp protein was found to decorate the ChO cap cells along their entire length, suggesting that the elongated cap cells are supported by the ECM to which they attach via integrin-based, Tsp-dependent, adhesion plaques. The ECM enwrapping the cap cells is probably important for keeping the cap cells fasciculate and may also provide mechanical support that allows the extremely elongated cells to maintain tension.

Bronchodilatory effect of deep inspiration in freshly isolated sheep lungs.

Taking a big breath is known to reverse bronchoconstriction induced by bronchochallenge in healthy subjects; this bronchodilatory effect of deep inspiration (DI) is diminished in asthmatics. The mechanism underlying the DI effect is not clear. Observations from experiments using isolated airway smooth muscle (ASM) preparations and airway segments suggest that straining of ASM due to DI could lead to bronchodilation, possibly due to strain-induced reduction in ASM contractility. However, factors external to the lung cannot be excluded as potential causes for the DI effect. Neural reflex initiated by stretch receptors in the lung are known to inhibit the broncho-motor tone and enhance vasodilatation; the former directly reduces airway resistance, and the latter facilitates removal of contractile agonists through the bronchial circulation. If the DI effect is solely mediated by factors extrinsic to the lung, the DI effect would be absent in isolated, nonperfused lungs. Here we examined the DI effect in freshly isolated, nonperfused sheep lungs. We found that imposition of DI on isolated lungs resulted in significant bronchodilation, that this DI effect was present only after the lungs were challenged with a contractile agonist (acetylcholine or histamine), and that the effect was independent of the difference in lung volume observed pre- and post-DI. We conclude that a significant portion of the bronchodilatory DI effect stems from factors internal to the lung related to the activation of ASM.

Respiratory modulation of startle eye blink: a new approach to assess afferent signals from the respiratory system.

Current approaches to assess interoception of respiratory functions cannot differentiate between the physiological basis of interoception, i.e. visceral-afferent signal processing, and the psychological process of attention focusing. Furthermore, they typically involve invasive procedures, e.g. induction of respiratory occlusions or the inhalation of CO2-enriched air. The aim of this study was to test the capacity of startle methodology to reflect respiratory-related afferent signal processing, independent of invasive procedures. Forty-two healthy participants were tested in a spontaneous breathing and in a 0.25 Hz paced breathing condition. Acoustic startle noises of 105 dB(A) intensity (50 ms white noise) were presented with identical trial frequency at peak and on-going inspiration and expiration, based on a new pattern detection method, involving the online processing of the respiratory belt signal. The results show the highest startle magnitudes during on-going expiration compared with any other measurement points during the respiratory cycle, independent of whether breathing was spontaneous or paced. Afferent signals from slow adapting phasic pulmonary stretch receptors may be responsible for this effect. This study is the first to demonstrate startle modulation by respiration. These results offer the potential to apply startle methodology in the non-invasive testing of interoception-related aspects in respiratory psychophysiology.This article is part of the themed issue 'Interoception beyond homeostasis: affect, cognition and mental health'.

Photodynamic therapy-induced nitric oxide production in neuronal and glial cells.

Nitric oxide (NO) has been recently demonstrated to enhance apoptosis of glial cells induced by photodynamic therapy (PDT), but to protect glial cells from PDT-induced necrosis in the crayfish stretch receptor, a simple neuroglial preparation that consists of a single mechanosensory neuron enveloped by satellite glial cells. We used the NO-sensitive fluorescent probe 4,5-diaminofluorescein diacetate to study the distribution and dynamics of PDT-induced NO production in the mechanosensory neuron and surrounding glial cells. The NO production in the glial envelope was higher than in the neuronal soma axon and dendrites both in control and in experimental conditions. In dark NO generator, DEA NONOate or NO synthase substrate L-arginine hydrochloride significantly increased the NO level in glial cells, whereas NO scavenger 2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO) or inhibitors of NO synthase L-NG-nitro arginine methyl ester and N?-nitro-L-arginine decreased it. PDT induced the transient increase in NO production with a maximum at 4 to 7 min after the irradiation start followed by its inhibition at 10 to 40 min. We suggested that PDT stimulated neuronal rather than inducible NO synthase isoform in glial cells, and the produced NO could mediate PDT-induced apoptosis.

Supraspinal control of spinal reflex responses to body bending during different behaviours in lampreys.

Spinal reflexes are substantial components of the motor control system in all vertebrates and centrally driven reflex modifications are essential to many behaviours, but little is known about the neuronal mechanisms underlying these modifications. To study this issue, we took advantage of an in vitro brainstem-spinal cord preparation of the lamprey (a lower vertebrate), in which spinal reflex responses to spinal cord bending (caused by signals from spinal stretch receptor neurons) can be evoked during different types of fictive behaviour. Our results demonstrate that reflexes observed during fast forward swimming are reversed during escape behaviours, with the reflex reversal presumably caused by supraspinal commands transmitted by a population of reticulospinal neurons. NMDA receptors are involved in the formation of these commands, which are addressed primarily to the ipsilateral spinal networks. In the present study the neuronal mechanisms underlying reflex reversal have been characterized for the first time. Spinal reflexes can be modified during different motor behaviours. However, our knowledge about the neuronal mechanisms underlying these modifications in vertebrates is scarce. In the lamprey, a lower vertebrate, body bending causes activation of intraspinal stretch receptor neurons (SRNs) resulting in spinal reflexes: activation of motoneurons (MNs) with bending towards either the contralateral or ipsilateral side (a convex or concave response, respectively). The present study had two main aims: (i) to investigate how these spinal reflexes are modified during different motor behaviours, and (ii) to reveal reticulospinal neurons (RSNs) transmitting commands for the reflex modification. For this purpose in in vitro brainstem-spinal cord preparation, RSNs and reflex responses to bending were recorded during different fictive behaviours evoked by supraspinal commands. We found that during fast forward swimming MNs exhibited convex responses. By contrast, during escape behaviours, MNs exhibited concave responses. We found RSNs that were activated during both stimulation causing reflex reversal without initiation of any specific behaviour, and stimulation causing reflex reversal during escape behaviour. We suggest that these RSNs transmit commands for the reflex modification. Application of the NMDA antagonist (AP-5) to the brainstem significantly decreased the reversed reflex, suggesting involvement of NMDA receptors in the formation of these commands. Longitudinal split of the spinal cord did not abolish the reflex reversal caused by supraspinal commands, suggesting an important role for ipsilateral networks in determining this type of motor response. This is the first study to reveal the neuronal mechanisms underlying supraspinal control of reflex reversal.

Vestibular Reflexes: Evaluation and Relevance in Microgravity

Maintaining postural equilibrium, sensing movement, and maintaining an awareness of the relative location of our body parts requires the precise integration of several of the body's sensory and response systems including visual, vestibular, somatosensory (touch, pressure, and stretch receptors in our skin, muscles, and joints), and auditory. Vestibular system plays important part in maintaining balance in microgravity environment. Understanding vestibular system and vestibular reflexes will help in training of space crew, detection of vestibular pathologies and prevention & treatment of space motion sickness. This review covers the vestibular reflex pathways, tests to check integrity of these pathways, effect of microgravity on vestibular system and role of vestibular system in space motion sickness