Layer V neurons in the primary motor cortex (M1) are important for motor skill learning. Since pretreatment of either CNQX or APV in rat M1 layer V impaired rotor rod learning, we analysed ...training‐induced synaptic plasticity by whole‐cell patch‐clamp technique in acute brain slices. Rats trained for 1 day showed a decrease in small inhibitory postsynaptic current (mIPSC) frequency and an increase in the paired‐pulse ratio of evoked IPSCs, suggesting a transient decrease in presynaptic GABA release in the early phase. Rats trained for 2 days showed an increase in miniature excitatory postsynaptic current (mEPSC) amplitudes/frequency and elevated AMPA/NMDA ratios, suggesting a long‐term strengthening of AMPA receptor‐mediated excitatory synapses. Importantly, rotor rod performance in trained rats was correlated with the mean mEPSC amplitude and the frequency obtained from that animal. In current‐clamp analysis, 1‐day‐trained rats transiently decreased the current‐induced firing rate, while 2‐day‐trained rats returned to pre‐training levels, suggesting dynamic changes in intrinsic properties. Furthermore, western blot analysis of layer V detected decreased phosphorylation of Ser408–409 in GABAA receptor β3 subunits in 1‐day‐trained rats, and increased phosphorylation of Ser831 in AMPA receptor GluA1 subunits in 2‐day‐trained rats. Finally, live‐imaging analysis of Thy1‐YFP transgenic mice showed that the training rapidly recruited a substantial number of spines for long‐term plasticity in M1 layer V neurons. Taken together, these results indicate that motor training induces complex and diverse plasticity in M1 layer V pyramidal neurons.
Key points
Here we examined motor training‐induced synaptic and intrinsic plasticity of layer V pyramidal neurons in the primary motor cortex.
The training reduced presynaptic GABA release in the early phase, but strengthened AMPA receptor‐mediated excitatory synapses in the later phase: acquired motor performance after training correlated with the strength of excitatory synapses rather than inhibitory synapses.
As to the intrinsic property, the training transiently decreased the firing rate in the early phase, but returned to pre‐training levels in the later phase.
Western blot analysis detected decreased phosphorylation of Ser408‐409 in GABAA receptor β3 subunits in the acute phase, and increased phosphorylation of Ser831 in AMPA receptor GluA1 subunits in the later phase.
Live‐imaging analysis of Thy1‐YFP transgenic mice showed rapid and long‐term spine plasticity in M1 layer V neurons, suggesting training‐induced increases in self‐entropy per spine.
figure legend Schematic of motor training and rapid spine dynamics in M1 layer V neurons. Exercise training promotes physiological and morphological spine diversity. Red: glutamate and AMPA receptors. Blue: GABA and GABAA receptors.
Abstract
The hippocampus is functionally heterogeneous between the dorsal and ventral subfields with left–right asymmetry. To determine the possible location of contextual memory, we performed an ...inhibitory avoidance task to analyze synaptic plasticity using slice patch-clamp technique. The training bilaterally increased the AMPA/NMDA ratio at dorsal CA3–CA1 synapses, whereas the training did not affect the ratio at ventral CA3–CA1 synapses regardless of the hemisphere. Moreover, sequential recording of miniature excitatory postsynaptic currents and miniature inhibitory postsynaptic currents from the same CA1 neuron clearly showed learning-induced synaptic plasticity. In dorsal CA1 neurons, the training dramatically strengthened both excitatory and inhibitory postsynaptic responses in both hemispheres, whereas the training did not promote the plasticity in either hemisphere in ventral CA1 neurons. Nonstationary fluctuation analysis further revealed that the training bilaterally increased the number of AMPA or GABAA receptor channels at dorsal CA1 synapses, but not at ventral CA1 synapses, suggesting functional heterogeneity of learning-induced receptor mobility. Finally, the performance clearly impaired by the bilateral microinjection of plasticity blockers in dorsal, but not ventral CA1 subfields, suggesting a crucial role for contextual learning. The quantification of synaptic diversity in specified CA1 subfields may help us to diagnose and evaluate cognitive disorders at the information level.
Background and Purpose
Mast cell hyperplasia has been observed in the lungs of mice with experimental asthma, but few reports have studied basophils. Here, we attempted to discriminate and quantify ...mast cells and basophils in the lungs in a murine asthma model, determine if both cells were increased by multiple antigen challenges and assess the roles of those cells in asthmatic responses.
Experimental Approach
Sensitized Balb/c mice were intratracheally challenged with ovalbumin four times. Mast cells and basophils in enzymatically digested lung tissue were detected by flow cytometry. An anti‐FcεRI monoclonal antibody, MAR‐1, was i.p. administered during the multiple challenges.
Key Results
The numbers of both mast cells (IgE+ C‐kit+) and basophils (IgE+ C‐kit− CD49b+) increased in the lungs after three challenges. Treatment with MAR‐1 completely abolished the increases; however, a late‐phase increase in specific airway resistance (sRaw), and airway eosinophilia and neutrophilia were not affected by the treatment, although the early‐phase increase in sRaw was suppressed. MAR‐1 reduced antigen‐induced airway IL‐4 production. Basophils infiltrating the lung clearly produced IL‐4 after antigen stimulation in vitro; however, histamine and murine mast cell protease 1 were not increased in the serum after the challenge, indicating that mast cell activation was not evoked.
Conclusion and Implications
Both mast cells and basophils infiltrated the lungs by multiple intratracheal antigen challenges in sensitized mice. Neither mast cells nor basophils were involved in late‐phase airway obstruction, although early‐phase obstruction was mediated by basophils. Targeting basophils in asthma therapy may be useful for an early asthmatic response.
H9N2 influenza viruses are frequently isolated from chicken meat and bone marrow imported from China to Japan since 2001. These isolates were experimentally inoculated into specific pathogen-free ...chickens intranasally. Viruses were recovered from the meat and bone marrow of birds showing no overt signs. On the other hand, chickens co-infected with H9N2 virus and either Staphylococcus aureus or Haemophilus paragallinarum showed clinical signs severer than those shown by birds infected only with the virus alone or each of the bacteria alone. In addition, H9N2 viruses were more efficiently recovered from the chickens co-infected with S. aureus or H. paragallinarum than those from the birds infected with only the virus. The present results indicate that co-infection of H9N2 influenza virus with S. aureus or H. paragallinarum enhances the replication of the virus in chickens, resulting in exacerbation of the H9N2 virus infection.
Background: Oscillometry is a tool to measure respiratory impedance that requires minimal patients' effort. In patients with chronic obstructive pulmonary disease (COPD), the correlation of ...respiratory impedance at rest with exertional ventilatory parameters, including exercise tolerance, has scarcely been reported. In addition, the utility of oscillometric parameters might differ between the inspiratory and expiratory phases due to airflow obstruction during expiration, but the hypothesis had not been validated. The aim of the present study was to investigate whether oscillometric parameters are associated with exertional ventilatory parameters in patients with COPD. Methods: Fifty-five subjects with COPD who attended clinics at the National Hospital Organization Osaka Toneyama Medical Center performed spirometry, oscillometry, and cardiopulmonary exercise testing (CPET) within 2 weeks. The correlations between parameters of spirometry, oscillometry, and CPET were analyzed using Spearman's rank correlation coefficient, univariate, and multivariate analyses. Results: Respiratory reactance had better correlations with the CPET parameters than respiratory resistance. Moreover, inspiratory reactance at rest correlated with the CPET parameters stronger than expiratory reactance. In particular, inspiratory resonant frequency (Fres-ins) correlated with peak oxygen uptake (r.sub.S=-0.549, p<0.01) and dead space to tidal volume ratio at peak exercise (r.sub.S=0.677, p<0.01) and the best predicted expiratory tidal volume (V.sub.T ex) at peak exercise of all the oscillometric parameters (r.sub.S=-0.679, p<0.01). However, the correlation between Fres-ins and V.sub.T ex at peak exercise became weak in subjects with severe and very severe COPD during exercise. Conclusion: Measurement of respiratory reactance is useful for the effortless evaluation of not only exertional ventilatory parameters but exercise tolerance in patients with COPD. The correlation of respiratory impedance with exertional ventilatory parameters can become weak in patients with advanced COPD; thus, the measurement of oscillometry might not be appropriate for evaluating exertional ventilatory parameters of patients with advanced COPD. Keywords: dyspnea, dynamic hyperinflation, airflow obstruction, resonant frequency, tidal volume
Summary
In Vietnam, live bird markets are found in most populated centres, providing the means by which fresh poultry can be purchased by consumers for immediate consumption. Live bird markets are ...aggregation points for large numbers of poultry, and therefore, it is common for a range of avian influenza viruses to be mixed within live bird markets as a result of different poultry types and species being brought together from different geographical locations. We conducted a cross‐sectional study in seven live bird markets in four districts of Thua Thien Hue Province in August and December, 2014. The aims of this study were to (i) document the prevalence of avian influenza in live bird markets (as measured by virus isolation); and (ii) quantify individual bird‐, seller‐ and market‐level characteristics that rendered poultry more likely to be positive for avian influenza virus at the time of sale. A questionnaire soliciting details of knowledge, attitude and avian influenza practices was administered to poultry sellers in study markets. At the same time, swabs and faecal samples were collected from individual poultry and submitted for isolation of avian influenza virus. The final data set comprised samples from 1,629 birds from 83 sellers in the seven live bird markets. A total of 113 birds were positive for virus isolation; a prevalence of 6.9 (95% CI 5.8–8.3) avian influenza virus‐positive birds per 100 birds submitted for sale. After adjusting for clustering at the market and individual seller levels, none of the explanatory variables solicited in the questionnaire were significantly associated with avian influenza virus isolation positivity. The proportions of variance at the individual market, seller and individual bird levels were 6%, 48% and 46%, respectively. We conclude that the emphasis of avian influenza control efforts in Vietnam should be at the individual seller level as opposed to the market level.
Outbreaks of highly pathogenic avian influenza (HPAI) have been occurring in domestic poultry in Asia since 1996. In the beginning of 2004, HPAI outbreaks were caused by H5N1 virus in two farms and a ...group of pet chickens in different areas of Japan. In the present study, the pathogenicity of A/chicken/Yamaguchi/7/04 (H5N1), which had been isolated from a dead chicken during the first outbreak in Japan, was assessed in chickens, quails, budgerigars, ducklings, mice, and miniature pigs by experimental infection. The virus was highly pathogenic to all the birds tested. Mice were susceptible to infection with a low mortality rate and miniature pigs were resistant to infection with the virus.
Intranasally inoculated neurotropic influenza viruses in mice infect not only the respiratory tract but also the central nervous system (CNS), mainly the brain stem.
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Previous studies ...suggested that the route of invasion of virus into the CNS was via the peripheral nervous system, especially the vagus nerve. To evaluate the transvagal transmission of the virus, we intranasally inoculated unilaterally vagectomized mice with a virulent influenza virus (strain 24a5b) and examined the distribution of the viral protein and genome by immunohistochemistry and in situ hybridization over time. An asymmetric distribution of viral antigens was observed between vagal (nodose) ganglia: viral antigen was detected in the vagal ganglion of the vagectomized side 2 days later than in the vagal ganglion of the intact side. The virus was apparently transported from the respiratory mucosa to the CNS directly and decussately via the vagus nerve and centrifugally to the vagal ganglion of the vagectomized side. The results of this study, thus, demonstrate that neurotropic influenza virus travels to the CNS mainly via the vagus nerve.
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