Cyclic AMP signaling contributes to neural plasticity and hyperexcitability in AH sensory neurons following intestinal Trichinella spiralis-induced inflammation

Trichinella spiralis infection causes hyperexcitability in enteric after-hyperpolarising (AH) sensory neurons that is mimicked by neural, immune or inflammatory mediators known to stimulate adenylyl cyclase (AC)/cyclic 3',5'-adenosine monophosphate (cAMP) signaling. The hypothesis was tested that ongoing modulation and sustained amplification in the AC/cAMP/phosphorylated cAMP related element binding protrein (pCREB) signaling pathway contributes to hyperexcitability and neuronal plasticity in gut sensory neurons after nematode infection. Electrophysiological, immunological, molecular biological or immunochemical studies were done in T. spiralis-infected guinea-pigs (8000 larvae or saline) after acute-inflammation (7 days) or 35 days p.i., after intestinal clearance. Acute-inflammation caused AH-cell hyperexcitability and elevated mucosal and neural tissue levels of myeloperoxidase, mast cell tryptase, prostaglandin E2, leukotrine B4, lipid peroxidation, nitric oxide and gelatinase; lower level inflammation persisted 35 days p.i. Acute exposure to blockers of AC, histamine, cyclooxygenase or leukotriene pathways suppressed AH-cell hyperexcitability in a reversible manner. Basal cAMP responses or those evoked by forskolin (FSK), Ro-20-1724, histamine or substance P in isolated myenteric ganglia were augmented after T. spiralis infection; up-regulation also occurred in AC expression and AC-immunoreactivity in calbindin (AH) neurons. The cAMP-dependent slow excitatory synaptic transmission-like responses to histamine (mast cell mediator) or substance P (neurotransmitter) acting via G-protein coupled receptors (GPCR) in AH neurons were augmented by up to 2.5-fold after T. spiralis infection. FSK, histamine, substance P or T. spiralis acute infection caused a 5- to 30-fold increase in cAMP-dependent nuclear CREB phosphorylation in isolated ganglia or calbindin (AH) neurons. AC and CREB phosphorylation remained elevated 35 days p.i.. Ongoing immune activation, AC up-regulation, enhanced phosphodiesterase IV activity and facilitation of the GPCR-AC/cAMP/pCREB signaling pathway contributes to T. spiralis-induced neuronal plasticity and AH-cell hyperexcitability. This may be relevant in gut nematode infections and inflammatory bowel diseases, and is a potential therapeutic target.     

FGFR1 and anosmin-1 underlying genetically distinct forms of Kallmann syndrome are co-expressed and interact in olfactory bulbs

Kallmann syndrome is a genetically heterogeneous developmental disease characterised by a partial or complete lack of olfactory bulb development. Two genes underlying this disease have so far been identified: the KAL-1 gene, which encodes anosmin-1, an extracellular matrix protein that promotes axonal guidance and branch formation in vitro; and KAL-2, which encodes the known FGFR1. The implication of FGFR1 and anosmin-1 in the same developmental disease led us to test whether anosmin-1 and FGFR1 interact during the development of the olfactory system. In this paper, we showed that the two proteins co-localise in the olfactory bulb during development in rat. Using cross-immunoprecipitation assays of olfactory bulb extracts, we also demonstrated that anosmin-1 and FGFR1 are comprised within the same protein complex. Moreover, we show that anosmin-1 expression in CHO transfected cells increases FGFR1 accumulation, suggesting that anosmin-1 may act as a positive extracellular regulator of FGFR1 signalling. Taken together, our findings strongly suggest that anosmin-1 is an essential component of a FGFR1 pathway that plays a key role during olfactory bulb morphogenesis.     

The role of vibrissal sensing in forelimb position control during travelling locomotion in the rat (Rattus norvegicus,Rodentia)

In the stem lineage of therians, a comprehensive reorganization of limb and body mechanics took place to provide dynamic stability for rapid locomotion in a highly structured environment. At what was probably the same time, mammals developed an active sense of touch in the form of movable mystacial vibrissae. The rhythmic movements of the limbs and vibrissae are controlled by central pattern-generating networks which might interact with each other in sensorimotor control. To test this possible interaction, we studied covariation between the two by investigating speed-dependent adjustments in temporal and spatial parameters of forelimb and vibrissal kinematics in the rat. Furthermore, the possible role of carpal vibrissae in connecting the two oscillating systems was explored. We compared locomotion on continuous and discontinuous substrates in the presence and absence of the mystacial or/and carpal vibrissae across a speed range of 0.2–0.5 m/s and found that a close coupling of the kinematics of the two oscillating systems appears to be precluded by their differential dependence on the animal's speed. Speed-related changes in forelimb kinematics mainly occur in temporal parameters, whereas vibrissae change their spatial excursion. However, whisking frequency is always high enough that at least one whisk cycle falls into the swing phase of the limb, which is the maximum critical period for sensing the substrate on which the forepaw will be placed. The influence of tactile cues on forelimb positional control is more subtle than expected. Tactile cues appear to affect the degree of parameter variation but not average parameters or the failure rate of limbs during walking on a perforated treadmill. The carpal vibrissae appear to play a role in sensing the animal's speed by measuring the duration of the stance phase. The absence of this cue significantly reduces speed-related variation in stride frequency and vibrissal protraction.     

Effects of highly selective sensory/motor nerve injury on bone metabolism and bone remodeling in rats

Objectives:This work aimed to investigate the mechanism of selective sensory/motor nerve injury in affecting bone metabolism and remodeling.Methods:The selective sensory/motor nerve injury rat model was constructed through posterior rhizotomy (PRG), anterior rhizotomy (ARG), or anterior combined with posterior rhizotomy (APRG) at the L_4-6 sensory/motor nerves on the right side of rats. Sham-operated (SOG) rats served as control. At 8 weeks after surgery, the sciatic nerves, spinal cord segments L₅ and tibial tissues were collected for analysis.Results:the integrity of trabecular bone was damaged, the number of trabecular bone was decreased and the number of osteoclasts were increased in ARG group. ARG activated NF-κβ and PPAR-γ pathways, and inhibited Wnt/β-catenin pathway. ARG group exhibited high turnover bone metabolism. In PRG group, the trabecular bone morphology became thinner, and the number of osteoclasts was increased. NF-κβ pathway was activated and OPG/RANKL ratio was decreased in PRG group. The activated osteoclasts, reduced osteoblasts activity and lower turnover bone metabolism were observed in PRG group. Additionally, the bone metabolism in APRG group was similar to ARG group.Conclusion:The posterior rhizotomy and anterior rhizotomy induced the different degree of osteoporosis in rats, which may attribute to regulate Wnt/β-catenin, NF-κβ and PPAR-γ signalling pathways.     

Effects of stimulus transformations on estimates of sensory neuron selectivity

Stimulus selectivity of sensory systems is often characterized by analyzing response-conditioned stimulus ensembles. However, in many cases these response-triggered stimulus sets have structure that is more complex than assumed. If not taken into account, when present it will bias the estimates of many simple statistics, and distort the estimated stimulus selectivity of a neural sensory system. We present an approach that mitigates these problems by modeling some of the response-conditioned stimulus structure as being generated by a set of transformations acting on a simple stimulus distribution. This approach corrects the estimates of key statistics and counters biases introduced by the transformations. In cases involving temporal spike jitter or spatial jitter of images, the main observed effects of transformations are blurring of the conditional mean and introduction of artefacts in the spectral decomposition of the conditional covariance matrix. We illustrate this approach by analyzing and correcting a set of model stimuli perturbed by temporal and spatial jitter. We apply the approach to neurophysiological data from the cricket cercal sensory system to correct the effects of temporal jitter. Action Editor: Matthew Wiener     

Sensory acquisition in active sensing systems

A defining feature of active sensing is the use of self-generated energy to probe the environment. Familiar biological examples include echolocation in bats and dolphins and active electrolocation in weakly electric fish. Organisms that utilize active sensing systems can potentially exert control over the characteristics of the probe energy, such as its intensity, direction, timing, and spectral characteristics. This is in contrast to passive sensing systems, which rely on extrinsic energy sources that are not directly controllable by the organism. The ability to control the probe energy adds a new dimension to the task of acquiring relevant information about the environment. Physical and ecological constraints confronted by active sensing systems include issues of signal propagation, attenuation, speed, energetics, and conspicuousness. These constraints influence the type of energy that organisms use to probe the environment, the amount of energy devoted to the process, and the way in which the nervous system integrates sensory and motor functions for optimizing sensory acquisition performance.     

A novel histidine kinase gene, ZmHK9, mediate drought tolerance through the regulation of stomatal development in Arabidopsis

Plants have developed complex signaling networks to regulate biochemical and physiological acclimation, environmental signals were perceived and transmitted to cellular machinery to activate adaptive responses. Here, a novel drought responsive histidine kinase gene was identified and designated as ZmHK9. Under normal conditions, ZmHK9 was predominantly expressed in roots, and the roots of ZmHK9-OX transgenic lines are markedly hypersensitive to ABA and ethylene, as compare to wild type. Consistent with its expression induced by PEG and exogenous ABA treatment, promoter sequence of this gene possessed drought and ABA responsive element. Moreover, the transgenic plants were much less affected by drought stress and recovered quickly after rewatering, stomatal complex size and stomatal density in the transgenic plants are significantly smaller and lower than those of the wild-type plants. In addition, ABA induced stomatal closure and the stomatal aperture of ZmHK9-OX lines was smaller than that of wild type. Collectively, it can be concluded that ZmHK9 regulates root elongation, stomatal development and drought tolerance through ABA dependent signaling pathway in Arabidopsis.     

Interfacing the neural system to restore deficient functions: from theoretical studies to neuroprothesis design

Electrical stimulation is a valuable technical solution to treat severe deficiencies related to nervous system. It is particularly interesting when no medical treatment exists as for cardiac deficiencies, deafness, blindness or complete paralysis. However, activating excitable cells such as neurons or muscle fibers to recover functions remains a difficult scientific and technological challenge. Indeed, both the function to restore and the way to activate selectively the desired target are not fully understood. The article describes how both theoretical studies based on experiments, and technological developments based on electrophysiology knowledge may help in the development of highly effective solutions. Existing systems such as pacemakers and cochlear implants proved that the recovered functions are of great quality leading to increase of quality of life and autonomy of the patients. However, the challenge for movement restoration is still in front of researchers, developers and clinical teams. The described method is the way we choose to face fundamental and tremendous scientific questions in order to provide disabled people with extended autonomy.     

Formal analysis of resonance entrainment by central pattern generator

The neuronal circuit controlling the rhythmic movements in animal locomotion is called the central pattern generator (CPG). The biological control mechanism appears to exploit mechanical resonance to achieve efficient locomotion. The objective of this paper is to reveal the fundamental mechanism underlying entrainment of CPGs to resonance through sensory feedback. To uncover the essential principle, we consider the simplest setting where a pendulum is driven by the reciprocal inhibition oscillator. Existence and properties of stable oscillations are examined by the harmonic balance method, which enables approximate but insightful analysis. In particular, analytical conditions are obtained under which harmonic balance predicts existence of an oscillation at a frequency near the resonance frequency. Our result reveals that the resonance entrainment can be maintained robustly against parameter perturbations through two distinct mechanisms: negative integral feedback and positive rate feedback.