The Japanese journal of physiology最新文献

{"title":"A unifying hypothesis for M1 muscarinic receptor signalling in pyramidal neurons","authors":"Sameera Dasari, C. Hill, Allan T. Gulledge","doi":"10.1113/JP273627","DOIUrl":"https://doi.org/10.1113/JP273627","url":null,"abstract":"Phasic release of acetylcholine (ACh) in the neocortex facilitates attentional processes. Acting at a single metabotropic receptor subtype, ACh exerts two opposing actions in cortical pyramidal neurons: transient inhibition and longer‐lasting excitation. Cholinergic inhibitory responses depend on calcium release from intracellular calcium stores, and run down rapidly at resting membrane potentials when calcium stores become depleted. We demonstrate that cholinergic excitation promotes calcium entry at subthreshold membrane potentials to rapidly refill calcium stores, thereby maintaining the fidelity of inhibitory cholinergic signalling. We propose a ‘unifying hypothesis’ for M1 receptor signalling whereby inhibitory and excitatory responses to ACh in pyramidal neurons represent complementary mechanisms governing rapid calcium cycling between the endoplasmic reticulum, the cytosol and the extracellular space.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"64 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72611893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New recipes with CaMPARI for ‘snapshots’ of synaptic circuit activity","authors":"Ronan Chéreau, A. Holtmaat","doi":"10.1113/JP273733","DOIUrl":"https://doi.org/10.1113/JP273733","url":null,"abstract":"The most powerful way to study cerebral network function and connectivity is by tracking the activity of large populations of neurons in relation to a stimulus or behaviour. Various techniques have been applied to monitor neuronal activity. For instance, labelling based on immediate early gene (IEG) expression (such as cFos and Arc) reveals a long-lasting trace of plasticity-related neuronal activity. This permits post hoc analysis in relatively large brain volumes, but it most likely excludes neurons exhibiting modest activity levels. On the contrary, calcium indicators such as GCaMPs (Chen et al. 2013) can report neuronal activity in real time with high sensitivity. However, due to the transient nature of calcium events, simultaneous visualization or post hoc analysis of activated neurons in large brain volumes proved to be challenging. Ideally, for functional synaptic circuit mapping, one would like to employ a method that combines the better of the enduring but somewhat enigmatic IEG-based labelling and the exact but fleeting calcium indicators. The recently developed activity reporter CaMPARI (calcium-modulated photoactivatable ratiometric integrator) potentially fulfils these requirements (Fosque et al. 2015). CaMPARI is a new type of fluorescent calcium indicator that efficiently undergoes an irreversible green-to-red conversion upon violet light illumination and binding of calcium (Fosque et al. 2015). The experimenter defines the time window of photoconversion, which can be repeatedly synchronized with a chosen stimulus. As a result, the intensity of red fluorescence scales with the sum of the calcium levels present at the time of all photoconversion epochs. This feature has been employed to generate a lasting ‘snapshot’ of evoked neuronal activity in various animal models such as zebrafish larvae, flies and in head fixed adult mice (Fosque et al. 2015). The study by Zolnik et al. (Zolnik et al. 2017), published in this issue of The Journal of Physiology, further characterizes and expands the possible applications of CaMPARI. They show that CaMPARI photoconversion is effective at low violet light intensities and linearly correlates with the dose of light (Fosque et al. 2015). This feature may extend the use of CaMPARI to experiments in which violet light delivery is challenging, such as in scattering tissue in vivo. The authors also cleverly employed CaMPARI’s sensitivity to reveal, in addition to spiking, sub-threshold synaptic activity in mouse brain slices, thereby offering a method for functional synaptic connectivity mapping. Subthreshold synaptic potentials typically generate localized dendritic calcium events, which are insufficient to be detected at the soma using transient calcium indicators. Nonetheless, Zolnik et al. demonstrate that repeatedly combining the violet light illumination with subthreshold stimulation causes a persistent accumulation of photoconverted CaMPARI at the soma. Thus, post hoc measurements based on CaMPAR","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"82 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82950311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loop G in the GABAA receptor α1 subunit influences gating efficacy","authors":"D. Baptista‐Hon, Simona Gulbinaite, T. Hales","doi":"10.1113/JP273752","DOIUrl":"https://doi.org/10.1113/JP273752","url":null,"abstract":"The functional importance of residues in loop G of the GABAA receptor has not been investigated. D43 and T47 in the α1 subunit are of particular significance as their structural modification inhibits activation by GABA. While the T47C substitution had no significant effect, non‐conservative substitution of either residue (D43C or T47R) reduced the apparent potency of GABA. Propofol potentiated maximal GABA‐evoked currents mediated by α1(D43C)β2γ2 and α1(T47R)β2γ2 receptors. Non‐stationary variance analysis revealed a reduction in maximal GABA‐evoked Popen, suggesting impaired agonist efficacy. Further analysis of α1(T47R)β2γ2 receptors revealed that the efficacy of the partial agonist THIP (4,5,6,7‐tetrahydroisoxazolo[5,4‐c]pyridine‐3‐ol) relative to GABA was impaired. GABA‐, THIP‐ and propofol‐evoked currents mediated by α1(T47R)β2γ2 receptors deactivated faster than those mediated by α1β2γ2 receptors, indicating that the mutation impairs agonist‐evoked gating. Spontaneous gating caused by the β2(L285R) mutation was also reduced in α1(T47R)β2(L285R)γ2 compared to α1β2(L285R)γ2 receptors, confirming that α1(T47R) impairs gating independently of agonist activation.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"147 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83103380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does trans‐spinal and local DC polarization affect presynaptic inhibition and post‐activation depression?","authors":"Dominik Kaczmarek, J. Ristikankare, Elzbieta Jankowska","doi":"10.1113/JP272902","DOIUrl":"https://doi.org/10.1113/JP272902","url":null,"abstract":"Trans‐spinal polarization was recently introduced as a means to improve deficient spinal functions. However, only a few attempts have been made to examine the mechanisms underlying DC actions. We have now examined the effects of DC on two spinal modulatory systems, presynaptic inhibition and post‐activation depression, considering whether they might weaken exaggerated spinal reflexes and enhance excessively weakened ones. Direct current effects were evoked by using local intraspinal DC application (0.3–0.4 μA) in deeply anaesthetized rats and were compared with the effects of trans‐spinal polarization (0.8–1.0 mA). Effects of local intraspinal DC were found to be polarity dependent, as locally applied cathodal polarization enhanced presynaptic inhibition and post‐activation depression, whereas anodal polarization weakened them. In contrast, both cathodal and anodal trans‐spinal polarization facilitated them. The results suggest some common DC‐sensitive mechanisms of presynaptic inhibition and post‐activation depression, because both were facilitated or depressed by DC in parallel.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87351281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal relationships between neurons of the nucleus incertus and the hippocampal theta activity in the rat","authors":"S. Martínez-Bellver, A. Cervera-Ferri, Aina Luque‐García, J. Martínez-Ricós, A. Valverde-Navarro, M. Bataller, Juan Guerrero, V. Teruel-Martí","doi":"10.1113/JP272841","DOIUrl":"https://doi.org/10.1113/JP272841","url":null,"abstract":"The nucleus incertus is a key node of the brainstem circuitry involved in hippocampal theta rhythmicity. Synchronisation exists between the nucleus incertus and hippocampal activities during theta periods. By the Granger causality analysis, we demonstrated a directional information flow between theta rhythmical neurons in the nucleus incertus and the hippocampus in theta‐on states. The electrical stimulation of the nucleus incertus is also able to evoke a phase reset of the hippocampal theta wave. Our data suggest that the nucleus incertus is a key node of theta generation and the modulation network.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84702057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in TRPC3 and TRPC6 channels assembly in mesenteric vascular smooth muscle cells in essential hypertension","authors":"I. Álvarez‐Miguel, P. Cidad, M. Pérez-García, J. López-López","doi":"10.1113/JP273327","DOIUrl":"https://doi.org/10.1113/JP273327","url":null,"abstract":"Canonical transient receptor potential (TRPC)3 and TRPC6 channels of vascular smooth muscle cells (VSMCs) mediate stretch‐ or agonist‐induced cationic fluxes, contributing to membrane potential and vascular tone. Native TRPC3/C6 channels can form homo‐ or heterotetrameric complexes, which can hinder individual TRPC channel properties. The possibility that the differences in their association pattern may change their contribution to vascular tone in hypertension is unexplored. Functional characterization of heterologously expressed channels showed that TRPC6‐containing complexes exhibited Pyr3/Pyr10‐sensitive currents, whereas TRPC3‐mediated currents were blocked by anti‐TRPC3 antibodies. VSMCs from hypertensive (blood pressure high; BPH) mice have larger cationic basal currents insensitive to Pyr10 and sensitive to anti‐TRPC3 antibodies. Consistently, myography studies showed a larger Pyr3/10‐induced vasodilatation in BPN (blood pressure normal) mesenteric arteries. We conclude that the increased TRPC3 channel expression in BPH VSMCs leads to changes in TRPC3/C6 heteromultimeric assembly, with a higher TRPC3 channel contribution favouring depolarization of hypertensive VSMCs.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73026278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diet‐induced dysmotility and neuropathy in the gut precedes endotoxaemia and metabolic syndrome: the chicken and the egg revisited","authors":"Yvonne Nyavor, O. Balemba","doi":"10.1113/JP273888","DOIUrl":"https://doi.org/10.1113/JP273888","url":null,"abstract":"Neuropathy of the enteric nervous system (ENS) is one of the major underlying causes of debilitating gastrointestinal (GI) motility disorders in diabetic patients. Recent studies suggest that diet–microbiome–host interactions – in particular, excess dietary calories, microbial metabolites, lipopolysaccharide (LPS) and disrupted mucosal barrier – play a fundamental role in the pathobiology of obesity and type II diabetes (Boulangé et al. 2016). Furthermore, the composition of the GI microbiome influences ENS physiology, neurochemistry and nerve cell health, as well as GI motility patterns, and vice versa (Kashyap et al. 2013). However, links between such interactions and the mechanisms underlying this neuropathy are not fully understood. In this issue of The Journal of Physiology, Reichardt et al. (2017) address the question of whether ingesting a Western diet (WD) rich in saturated fatty acids and the associated alteration to the gut microbiome disrupts motility, and induces loss of nitrergic myenteric neurons (NMNs), the phenotype that is commonly damaged in diabetic neuropathy (Yarandi & Srinivasan, 2014). The rationale is that most studies have used a high fat diet (HFD; 60–72% kcal from fat), leading to little understanding of how a normal WD affects GI motility, the ENS and their role in the pathobiology of the metabolic syndrome and diabetes. The authors used C57BL/6 mice fed WD (35% kcal from fat, enriched in palmitate) or a regular diet (RD, 16.9% kcal from fat, 4× less palmitate) for 3, 6, 9 and 12 weeks, and TLR4 and germ free mice fed WD and RD diets for 6 weeks. Gastrointestinal motility was measured, and damage to myenteric neurons and NMNs was studied in the ileum and proximal colon. Palmitateand LPS-induced damage to NMNs and the role of nitric oxide synthase (nNOS) in such injury were determined in vitro using immortalized myenteric neurons. Faecal metabolites, systemic and visceral fat and mucosal inflammation were analysed. After ingesting WD for 6 weeks, mice were ‘overweight’, developed gut microbiota dysbiosis, altered faecal metabolites, increased intraluminal LPS and increased plasma free fatty acid (FFA) levels. Interestingly, unlike HFD, WD did not elicit hyperglycaemia, endotoxaemia and inflammation, suggesting the need to define key differences between the effect of HFD and WD on gut microbiome and metabolic profiles. Another important observation was that WD caused GI dysmotility before","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80765163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How and why are calcium currents curtailed in the skeletal muscle voltage‐gated calcium channels?","authors":"B. Flucher, Petronel Tuluc","doi":"10.1113/JP273423","DOIUrl":"https://doi.org/10.1113/JP273423","url":null,"abstract":"Voltage‐gated calcium channels represent the sole mechanism converting electrical signals of excitable cells into cellular functions such as contraction, secretion and gene regulation. Specific voltage‐sensing domains detect changes in membrane potential and control channel gating. Calcium ions entering through the channel function as second messengers regulating cell functions, with the exception of skeletal muscle, where CaV1.1 essentially does not function as a channel but activates calcium release from intracellular stores. It has long been known that calcium currents are dispensable for skeletal muscle contraction. However, the questions as to how and why the channel function of CaV1.1 is curtailed remained obscure until the recent discovery of a developmental CaV1.1 splice variant with normal channel functions. This discovery provided new means to study the molecular mechanisms regulating the channel gating and led to the understanding that in skeletal muscle, calcium currents need to be restricted to allow proper regulation of fibre type specification and to prevent mitochondrial damage.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"1 1","pages":"1451 - 1463"},"PeriodicalIF":0.0,"publicationDate":"2017-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89026084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tracking motor units longitudinally across experimental sessions with high‐density surface electromyography","authors":"E. Martinez‐Valdes, F. Negro, Christopher M. Laine, Deborah Falla, Frank Mayer, Dario Farina, Dario Farina","doi":"10.1113/JP273662","DOIUrl":"https://doi.org/10.1113/JP273662","url":null,"abstract":"Classic motor unit (MU) recording and analysis methods do not allow the same MUs to be tracked across different experimental sessions, and therefore, there is limited experimental evidence on the adjustments in MU properties following training or during the progression of neuromuscular disorders. We propose a new processing method to track the same MUs across experimental sessions (separated by weeks) by using high‐density surface electromyography. The application of the proposed method in two experiments showed that individual MUs can be identified reliably in measurements separated by weeks and that changes in properties of the tracked MUs across experimental sessions can be identified with high sensitivity. These results indicate that the behaviour and properties of the same MUs can be monitored across multiple testing sessions. The proposed method opens new possibilities in the understanding of adjustments in motor unit properties due to training interventions or the progression of pathologies.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"9 1","pages":"1479 - 1496"},"PeriodicalIF":0.0,"publicationDate":"2017-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86696060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synaptic vesicle pool‐specific modification of neurotransmitter release by intravesicular free radical generation","authors":"Olusoji A. T. Afuwape, Catherine R. Wasser, T. Schikorski, E. Kavalali","doi":"10.1113/JP273115","DOIUrl":"https://doi.org/10.1113/JP273115","url":null,"abstract":"Synaptic transmission is mediated by the release of neurotransmitters from synaptic vesicles in response to stimulation or through the spontaneous fusion of a synaptic vesicle with the presynaptic plasma membrane. There is growing evidence that synaptic vesicles undergoing spontaneous fusion versus those fusing in response to stimuli are functionally distinct. In this study, we acutely probe the effects of intravesicular free radical generation on synaptic vesicles that fuse spontaneously or in response to stimuli. By targeting vesicles that preferentially release spontaneously, we can dissociate the effects of intravesicular free radical generation on spontaneous neurotransmission from evoked neurotransmission and vice versa. Taken together, these results further advance our knowledge of the synapse and the nature of the different synaptic vesicle pools mediating neurotransmission.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83425656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}