Journal of Physiology-London最新文献

{"title":"Systolic and diastolic dysfunction is exacerbated by age and spinal cord injury in male and female mice with central nervous system serotonin deficiency","authors":"Qingchao Qiu, Dragana Komnenov, Mirabela Hali, Charles S. Chung, Patrick J. Mueller, Noreen F. Rossi, Donald M. Kuhn, Jason H. Mateika","doi":"10.1113/JP287067","DOIUrl":"10.1113/JP287067","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <div>The present study was designed to explore whether the depletion of serotonin (5-HT) in the central nervous system (CNS<sup>5-HT</sup>) leads to systolic and diastolic dysfunction and whether this dysfunction is exacerbated by sex, age and spinal cord injury. Echocardiographic assessment of systolic and diastolic function was completed in young and old male and female tryptophan hydroxylase 2 knockout (TPH2<sup>−/−</sup>) and wild-type (TPH2<sup>+/+</sup>) mice with intact spinal cords, as well as in C<sub>2 </sub> spinal cord hemisected young TPH2<sup>−/−</sup> and TPH2<sup>+/+</sup> mice. In addition, lumbar sympathetic nervous system activity was recorded in elderly male and female intact TPH2<sup>−/−</sup> and TPH2<sup>+/+</sup> mice. Systolic and diastolic dysfunction was evident in young TPH2<sup>−/−</sup> mice, including a higher left ventricular mass (<i>P</i> < 0.001), left ventricular outflow parameters (e.g. peak velocity) and E/A (<i>P</i> < 0.001). Reductions in ejection fraction and fractional shortening were also evident (<i>P</i> < 0.001), although stroke volume and cardiac output were maintained. The assessed dysfunction was exacerbated by age and spinal cord injury, resulting in reductions in cardiac output (<i>P</i> ≤ 0.01). The dysfunction was accompanied by increases in sympathetic burst height (<i>P</i> = 0.038) and incidence (<i>P</i> = 0.001). Reductions in CNS<sup>5-HT</sup> are coupled to systolic and diastolic dysfunction, which is exacerbated by age and spinal cord injury. This dysfunction is coupled to increases in sympathetic nervous system activity in elderly mice. Our findings are an initial step toward determining whether reductions in CNS<sup>5-HT</sup> are a unifying mechanism that links central sleep apnoea, sympathoexcitation and heart failure in intact and spinal cord injured individuals.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key points</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Reductions in central nervous system serotonin (CNS<sup>5-HT</sup>) may contribute to systolic and diastolic dysfunction. This dysfunction may be linked to increases in sympathetic nervous system activity and exacerbated by sex, age and spinal cord injury.</li>\u0000 \u0000 <li>Echocardiographic assessment of systolic and diastolic function was completed in young and old male and female intact TPH2<sup>+/+</sup> and TPH2<sup>−/−</sup> mice, as well as in C<sub>2 </sub>spinal cord hemisected young mice. Lumbar sympathetic nervous system activity was also recorded in elderly male","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 6","pages":"1375-1397"},"PeriodicalIF":4.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1113/JP287067","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial control of ciliary gene expression and structure in striatal neurons.","authors":"Dogukan H Ulgen, Alessandro Chioino, Olivia Zanoletti, Albert Quintana, Elisenda Sanz, Carmen Sandi","doi":"10.1113/JP287948","DOIUrl":"https://doi.org/10.1113/JP287948","url":null,"abstract":"<p><p>Mitochondria play essential metabolic roles and are increasingly understood to interact with other organelles, influencing cellular function and disease. Primary cilia, as sensory and signalling organelles, are crucial for neuronal communication and function. Emerging evidence suggests that mitochondria and primary cilia may interact to regulate cellular processes, as recently shown in brain cells such as astrocytes. Here, we investigated whether mitochondria also regulate primary cilia in neurons, focusing on molecular pathways linking both organelles and structural components within cilia. We employed a cross-species, molecular pathway-focused approach to explore connections between mitochondrial and ciliary pathways in neurons, revealing strong associations suggesting coordinated functionality. Furthermore, we found that viral-induced downregulation of the mitochondrial fusion gene mitofusin 2 (Mfn2) in dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs) of the nucleus accumbens (NAc) altered ciliary gene expression, with Crocc - the gene encoding rootletin - showing the most pronounced downregulation. This reduction in Crocc expression was linked to decreased levels of rootletin protein, a key structural component of the ciliary rootlet. Notably, viral-mediated overexpression of rootletin restored ciliary complexity and elongation, without compromising neuronal adaptation to Mfn2 downregulation. Our findings provide novel evidence of a functional mitochondria-cilia interaction in neurons, specifically in striatal D1-MSNs. These results reveal a previously unrecognized role of mitochondrial dynamics in regulating ciliary structure in neurons, with potential implications for neuropsychiatric and neurodegenerative disease mechanisms. KEY POINTS: Mitochondria are cell structures known for producing energy but are also emerging as regulators of other cellular components, including primary cilia, antenna-like structures involved in cell communication. Previous studies suggest that mitochondria may influence cilia structure and function, including in astrocytes. However, this has not been explored in neurons. This study shows that natural variation in mitochondrial molecular pathways correlates with primary cilia pathways in striatal medium spiny neurons in both rats and mice. Reducing expression of mitofusin 2 (Mfn2), a key mitochondrial protein involved in fusion and mitochondria-endoplasmic reticulum interactions, changes specific molecular ciliary pathways, notably including Crocc, a gene essential for cilia structure, and reduces the levels of its protein product, rootletin, which supports cilia integrity. Our findings reveal an important role for mitochondria in regulating ciliary structure in neurons, highlighting a potential pathway for mitochondrial regulation of neuronal signalling.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flexible control of motor units: is the multidimensionality of motor unit manifolds a sufficient condition?","authors":"François Dernoncourt, Simon Avrillon, Tijn Logtens, Thomas Cattagni, Dario Farina, François Hug","doi":"10.1113/JP287857","DOIUrl":"https://doi.org/10.1113/JP287857","url":null,"abstract":"<p><p>Understanding flexibility in the neural control of movement requires identifying the distribution of common inputs to the motor units. In this study, we identified large samples of motor units from two lower limb muscles: the vastus lateralis (VL; up to 60 motor units per participant) and the gastrocnemius medialis (GM; up to 67 motor units per participant). First, we applied a linear dimensionality reduction method to assess the dimensionality of the manifolds underlying the motor unit activity. We subsequently investigated the flexibility in motor unit control under two conditions: sinusoidal contractions with torque feedback, and online control with visual feedback on motor unit firing rates. Overall, we found that the activity of GM motor units was effectively captured by a single latent factor defining a unidimensional manifold, whereas the VL motor units were better represented by three latent factors defining a multidimensional manifold. Despite this difference in dimensionality, the recruitment of motor units in the two muscles exhibited similarly low levels of flexibility. Using a spiking network model, we tested the hypothesis that dimensionality derived from factorization does not solely represent descending cortical commands but is also influenced by spinal circuitry. We demonstrated that a heterogeneous distribution of inputs to motor units, or specific configurations of recurrent inhibitory circuits, could produce a multidimensional manifold. This study clarifies an important debated issue, demonstrating that while motor unit firings of a non-compartmentalized muscle can lie in a multidimensional manifold, the CNS may still have limited capacity for flexible control of these units. KEY POINTS: To generate movement, the CNS distributes both excitatory and inhibitory inputs to the motor units. The level of flexibility in the neural control of these motor units remains a topic of debate with significant implications for identifying the smallest unit of movement control. By combining experimental data and in silico models, we demonstrated that the activity of a large sample of motor units from a single muscle can be represented by a multidimensional linear manifold; however, these units show very limited flexibility in their recruitment. The dimensionality of the linear manifold may not directly reflect the dimensionality of descending inputs but could instead relate to the organization of local spinal circuits.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modelling the time-resolved modulations of cardiac activity in rats: A study on pharmacological autonomic stimulation.","authors":"Diego Candia-Rivera, Sofia Carrion-Falgarona, Fabrizio de Vico Fallani, Mario Chavez","doi":"10.1113/JP288400","DOIUrl":"https://doi.org/10.1113/JP288400","url":null,"abstract":"<p><p>Assessing cardiac dynamics over time is essential for understanding cardiovascular health and its parallel patterns of activity with the brain. We present a methodology to estimate the time-resolved sympathetic and parasympathetic modulations of cardiac dynamics, specifically tailored for the rat heart. To evaluate the performance of our method, we study a dataset comprising spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. These rats were administered dobutamine to elicit autonomic dynamics. The results obtained from our method demonstrated accurate time-resolved depiction of sympathetic reactivity induced by dobutamine administration. These responses closely resembled the expected autonomic alterations observed during physical exercise conditions, albeit emulated pharmacologically. We further compared our method with standard measures of low-frequency (LF) and high-frequency (HF) components, which are commonly used, although debated, for sympathetic and parasympathetic activity estimation. The comparisons with LF and HF measures further confirmed the effectiveness of our method in better capturing autonomic changes in rat cardiac dynamics. Our findings highlight the potential of our adapted method for time-resolved analysis in future clinical and translational studies involving rodent models. The validation of our approach in animal models opens new avenues for investigating the relationship between ongoing changes in cardiac activity and parallel changes in brain dynamics. Such investigations are crucial for advancing our understanding of the brain-heart connection, particularly in cases involving neurodegeneration, brain injuries and cardiovascular conditions. KEY POINTS: We developed a method for time-resolved estimation of sympathetic and parasympathetic modulations in rat cardiac dynamics, validated against standard low-frequency and high-frequency measures. We used a cohort of spontaneously hypertensive rats and Wistar-Kyoto rats, with dobutamine administration to induce autonomic responses. Our method accurately depicted time-resolved sympathetic reactivity similar to autonomic changes during physical exercise. Our findings suggest potential for future clinical and translational studies on the brain-heart connection, particularly in cardiovascular conditions.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial efficiency in resting skeletal muscle in vivo: a novel non-invasive approach using multinuclear magnetic resonance spectroscopy in humans","authors":"Muhammet Enes Erol,&nbsp;Sean T. Bannon,&nbsp;Alexs A. Matias,&nbsp;Triantafyllia Siokas,&nbsp;Rajakumar Nagarajan,&nbsp;Yann Le Fur,&nbsp;Song-Young Park,&nbsp;Gwenael Layec","doi":"10.1113/JP287412","DOIUrl":"10.1113/JP287412","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 \u0000 &lt;div&gt;Mitochondrial efficiency is a critical metabolic parameter with far-reaching implications for tissue homeostasis. However, the direct measurement of oxygen consumption (VO&lt;sub&gt;2&lt;/sub&gt;) and ATP production from a large tissue sample &lt;i&gt;in vivo&lt;/i&gt; remains challenging. Using phosphorus (&lt;sup&gt;31&lt;/sup&gt;P) and proton (&lt;sup&gt;1&lt;/sup&gt;H) magnetic resonance spectroscopy (MRS), this study aimed to non-invasively quantify the skeletal muscle ATP synthesis rate and VO&lt;sub&gt;2&lt;/sub&gt; to determine mitochondrial efficiency at rest and during muscle contraction in humans. We assessed mitochondrial efficiency in the plantar flexor muscles of 12 healthy adults (21 ± 1 years) using &lt;sup&gt;31&lt;/sup&gt;P and &lt;sup&gt;1&lt;/sup&gt;H MRS within a 3T MR system. MRS data were acquired at rest and during constant workloads to quantify oxidative ATP synthesis (ATP&lt;sub&gt;ox&lt;/sub&gt;) rate and myoglobin-derived oxygen consumption (Mb-derived VO&lt;sub&gt;2&lt;/sub&gt;). At rest, ATP&lt;sub&gt;ox&lt;/sub&gt; was 0.85 ± 0.24 m&lt;span&gt;m&lt;/span&gt; min&lt;sup&gt;−1,&lt;/sup&gt; and Mb-derived VO&lt;sub&gt;2&lt;/sub&gt; was 0.46 ± 0.11 m&lt;span&gt;m&lt;/span&gt; min&lt;sup&gt;−1&lt;/sup&gt;, resulting in a P/O ratio of 1.95 ± 0.68. During graded exercise, end-exercise PCr concentration decreased from 29 ± 5.7 m&lt;span&gt;m&lt;/span&gt; to 18 ± 4.8 m&lt;span&gt;m&lt;/span&gt;, and end-exercise Mb oxygenation declined linearly to 47 ± 11%. ATP&lt;sub&gt;ox&lt;/sub&gt; synthesis rate increased linearly with exercise workload (&lt;i&gt;r&lt;/i&gt; = 0.65 ± 0.31), whereas there was no significant change in Mb-derived VO&lt;sub&gt;2&lt;/sub&gt; (&lt;i&gt;r&lt;/i&gt; = −0.19 ± 0.60), leading to non-physiological P/O values during exercise (&gt;3). The results indicate that combined &lt;sup&gt;31&lt;/sup&gt;P/&lt;sup&gt;1&lt;/sup&gt;H-MRS at rest offers a promising approach for non-invasively quantifying mitochondrial efficiency in large muscle samples, suggesting its potential as a clinical endpoint of mitochondrial function. However, further refinement is needed for use during exercise.\u0000\u0000 &lt;figure&gt;\u0000 &lt;div&gt;&lt;picture&gt;\u0000 &lt;source&gt;&lt;/source&gt;&lt;/picture&gt;&lt;p&gt;&lt;/p&gt;\u0000 &lt;/div&gt;\u0000 &lt;/figure&gt;\u0000 &lt;/div&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Key points&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;Mitochondrial efficiency, converting chemical energy from carbon fuels into ATP, is a vital metabolic parameter for tissue homeostasis, but measuring oxygen consumption (VO&lt;sub&gt;2&lt;/sub&gt;) and ATP production &lt;i&gt;in vivo&lt;/i&gt; has been challenging.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;This study used phosphorus (&lt;sup&gt;31&lt;/sup&gt;P) and proton (&lt;sup&gt;1&lt;/sup&gt;H) magnetic resonance spectroscopy (MRS) to non-invasively quantify the skeletal muscle ATP synthesis rate and VO&lt;sub&gt;2&lt;/sub&gt; at rest and during muscle contraction in humans.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;At rest","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 6","pages":"1503-1519"},"PeriodicalIF":4.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1113/JP287412","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determining properties of human-induced pluripotent stem cell-derived cardiomyocytes using spatially resolved electromechanical metrics.","authors":"Karoline Horgmo Jæger, Verena Charwat, Kevin E Healy, Samuel Wall, Aslak Tveito","doi":"10.1113/JP287275","DOIUrl":"https://doi.org/10.1113/JP287275","url":null,"abstract":"<p><p>Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are increasingly important in preclinical drug assessments, particularly for identifying potential cardiotoxicity. In this study, we utilize data from microphysiological systems of hiPSC-CMs to evaluate cellular characteristics, such as action potential duration, beat rate, conduction velocity and mechanical displacement. Based on these data, high-fidelity mathematical models facilitate precise assessments of critical biophysical parameters of the cells, including membrane ion channel conductances, cross-bridge cycle transition rates and cell-to-cell conductance. We emphasize the distinction between synchronized transients and travelling waves, highlighting their implications for deducing the biophysical properties of hiPSC-CMs. In this study, we analyse the effects of the drug compounds flecainide, quinidine, nifedipine, verapamil, blebbistatin and omecamtiv. Our findings show that for drug-induced changes in parameters describing membrane currents and contractile machinery close to ranges reported in the literature, the computed biomarkers align well with measured biomarkers. This study is the first to apply spatially resolved, cell-based models to identify drug effects through measurements of transmembrane potential and mechanical displacement, marking a significant step forward in using computational models for evaluating drug safety and offering a new approach to early identification of adverse drug reactions. KEY POINTS: Optical measurements of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) present significant opportunities to advance understanding of how human heart cells function and interact. Although direct optical measurements yield valuable biomarkers, they fall short of revealing underlying biophysical properties, for example, how novel drug compounds perturb the ion channels. Drug properties are best understood through computational models that capture cell dynamics based on physical laws. Traditionally, data and models have been averaged over all cells in cell collections, thus overlooking spatiotemporal waves. Here, we use recently developed cell-based models, representing spatial dynamics including cell-to-cell electrical and mechanical coupling, to determine biophysical properties of collections of hiPSC-CMs.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebral blood flow during simulated central hypovolaemia in people with hypertension: does vertebral artery hypoplasia matter?","authors":"Sandra Neumann,&nbsp;Jonathan C. L. Rodrigues,&nbsp;Lydia L. Simpson,&nbsp;Chris B. Lawton,&nbsp;Daniel Burden,&nbsp;Matthew D. Kobetic,&nbsp;Zoe H. Adams,&nbsp;Katrina Hope,&nbsp;Julian F. R. Paton,&nbsp;Hazel Blythe,&nbsp;Nathan Manghat,&nbsp;Jill N. Barnes,&nbsp;Angus K. Nightingale,&nbsp;Mark C. H. Hamilton,&nbsp;Emma C. Hart","doi":"10.1113/JP287786","DOIUrl":"10.1113/JP287786","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 \u0000 &lt;div&gt;Adults with hypertension have higher prevalence of vertebral artery hypoplasia (VAH), which is associated with lower resting cerebral blood flow (CBF). We examined whether VAH impacts the ability to regulate CBF during haemodynamic stress when cardiac output and blood pressure are lowered via body negative pressure (LBNP). Participants underwent magnetic resonance angiography (MRA) at 1.5T during LBNP at 0, −20 and −40 mmHg, and were assigned to VAH (&lt;i&gt;n&lt;/i&gt; = 13) or without-VAH (&lt;i&gt;n&lt;/i&gt; = 11) groups post-acquisition. Phase-contrast MRA measured flow in the basilar artery (BA), internal carotid arteries (ICA), and the ascending aorta to measure cardiac output (CO). The CO decreased during all levels of LBNP in both groups (LBNP main effect &lt;i&gt;P&lt;/i&gt; &lt; 0.0001), whereas MAP was reduced in the group without VAH only (&lt;i&gt;P&lt;/i&gt; = 0.0003). BA flow was reduced during LBNP in the group without VAH (&lt;i&gt;P&lt;/i&gt; = 0.0267 at −20 mmHg and &lt;i&gt;P&lt;/i&gt; &lt; 0.0001 at −40 mmHg) but was surprisingly unchanged in the group with VAH (&lt;i&gt;P&lt;/i&gt; &gt; 0.05 all levels LBNP). ICA flow decreased during LBNP (&lt;i&gt;P&lt;/i&gt; &lt; 0.0001) and was not different between groups. Total CBF decreased during LBNP in hypertensives without VAH (&lt;i&gt;P&lt;/i&gt; = 0.0192 at −20 mmHg and &lt;i&gt;P&lt;/i&gt; &lt; 0.0001 at −40 mmHg) but was unchanged in patients with VAH (&lt;i&gt;P&lt;/i&gt; &gt; 0.05 at all levels of LBNP). Total peripheral resistance (TPR) increased during LBNP in both groups, but the rise was greater in the group with VAH (−20 mmHg; &lt;i&gt;P&lt;/i&gt; = 0.0129, –40 mmHg; &lt;i&gt;P&lt;/i&gt; = 0.0016). In summary, hypertensive patients without VAH may tolerate decreases in CBF, whereas patients with VAH evoke a greater systemic TPR response to preserve CBF.\u0000\u0000 &lt;figure&gt;\u0000 &lt;div&gt;&lt;picture&gt;\u0000 &lt;source&gt;&lt;/source&gt;&lt;/picture&gt;&lt;p&gt;&lt;/p&gt;\u0000 &lt;/div&gt;\u0000 &lt;/figure&gt;\u0000 &lt;/div&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Key points&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;Vertebral artery hypoplasia (VAH) is more common in hypertensive adults and is associated with lower resting cerebral blood flow (CBF), suggesting that VAH might impair the brain's ability to maintain cerebral blood flow during haemodynamic stress using lower body negative pressure.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;This study shows that hypertensive patients with VAH maintain CBF during body negative pressure, unlike those without VAH, who experience reductions in CBF. Patients with VAH show a greater rise in total peripheral resistance (TPR), suggesting a compensatory mechanism to maintain cerebral perfusion.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;The findings highlight that patients with VAH have an altered physiological respon","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 6","pages":"1417-1437"},"PeriodicalIF":4.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1113/JP287786","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Goal-directed action preparation in humans entails a mixture of corticospinal neural computations","authors":"Corey G. Wadsley,&nbsp;Thuan Nguyen,&nbsp;Chris Horton,&nbsp;Ian Greenhouse","doi":"10.1113/JP287939","DOIUrl":"10.1113/JP287939","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <div>The seemingly effortless ability of humans to transition from thinking about actions to initiating them relies on sculpting corticospinal (CS) output from the primary motor cortex. The present study tested whether canonical additive and multiplicative neural computations, well-described in sensory systems, generalize to the CS pathway during human action preparation. We used non-invasive brain stimulation to measure CS input–output across varying action preparation contexts during instructed-delay finger response tasks. Goal-directed action preparation was marked by increased multiplicative gain of CS projections to task-relevant muscles and additive suppression of CS projections to non-selected and task-irrelevant muscles. Individuals who modulated CS gain to a greater extent were faster to initiate prepared responses. Our findings provide physiological evidence of combined additive suppression and gain modulation in the human motor system. We propose that these computations support action preparation by enhancing the contrast between selected motor representations and surrounding background activity to facilitate response selection and execution.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key points</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Neural computations determine what information is transmitted through brain circuits.</li>\u0000 \u0000 <li>We investigated whether the motor system uses computations similar to those observed in sensory systems by non-invasively stimulating the corticospinal pathway in humans during goal-directed action preparation.</li>\u0000 \u0000 <li>We discovered physiological evidence indicating that corticospinal projections to behaviourally relevant muscles exhibit non-linear gain computations, whereas projections to behaviourally irrelevant muscles exhibit linear suppression.</li>\u0000 \u0000 <li>Our findings suggest that certain computational principles generalize to the human motor system and serve to enhance the contrast between relevant and background neural activity.</li>\u0000 \u0000 <li>These results indicate that neural computations during goal-directed action preparation may support motor control by increasing signal-to-noise within the corticospinal pathway.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 6","pages":"1589-1605"},"PeriodicalIF":4.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early sensorimotor restriction in rats induces age-dependent mitochondrial alterations in skeletal muscles and brain structures.","authors":"Mélanie Van Gaever, Olivier Dupuy, Erwan Dupont, Marie-Hélène Canu, Frederic Daussin","doi":"10.1113/JP287765","DOIUrl":"https://doi.org/10.1113/JP287765","url":null,"abstract":"<p><p>A sedentary lifestyle can lead to motor and cognitive deficits, increasing the risk of neurodegenerative diseases in ageing. Emerging hypotheses suggest that these functional alterations may be related to energy metabolism. Indeed, ATP produced by mitochondria is essential for muscle contraction, neurotransmission and brain plasticity processes. Although a sedentary lifestyle has been associated with mitochondrial alterations in skeletal muscle, the potential effects on brain structures have yet to be investigated. The present study aimed to determine whether early sensorimotor restriction (SMR) alters mitochondrial metabolism in rat muscles and brain structures. Enzyme activities of citrate synthase (CS) and respiratory chain complexes I, II and IV were measured using a spectrophotometric technique and mitochondrial respiration was assessed using high-resolution respirometry in two hind limb muscles [soleus and extensor digitorum longus (EDL)] and four brain structures (sensorimotor cortex, striatum, prefrontal cortex and hippocampus) in control rats and rats experiencing early SMR from birth to day 28. Mitochondrial enzyme activities decreased in the soleus (complexes I and II), in the EDL (complex I) and in the hippocampus (complexes I and IV) in an age-dependent manner, whereas no effect was observed in other brain structures. CS activity decreases in the soleus and increases transiently in the striatum and sensorimotor cortex at postnatal day 15. Mitochondrial respiration was reduced in the soleus and in the sensorimotor cortex (CI and CI+CII). Early SMR appears to induce quantitative and qualitative mitochondrial alterations in skeletal muscles and certain brain structures involved in cognitive and motor processes. KEY POINTS: Early sensorimotor restriction (SMR) alters mitochondrial enzyme activities and mitochondrial respiration in skeletal muscles and brain. Mitochondrial alterations induced by early SMR are age-dependent, structure-dependent and complex-dependent. Mitochondrial enzyme activities increase during development and the evolution pattern is specific to the different structures.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The visual representation of 3D orientation in macaque areas STPp and VPS","authors":"Rong Wang,&nbsp;Bin Zhao,&nbsp;Aihua Chen","doi":"10.1113/JP287309","DOIUrl":"10.1113/JP287309","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <div>In the current study, we investigated the neural mechanisms underlying the representation of three-dimensional (3D) surface orientation within the posterior portion of the superior temporal polysensory area (STPp) and the visual posterior Sylvian area (VPS) in the macaque brain. Both areas are known for their integration of visual and vestibular signals, which are crucial for visual stability and spatial perception. However, it remains unclear how exactly these areas represent the orientation of 3D surfaces. To tackle this question, we used random dot stereograms (RDS) to present 3D planar stimuli defined by slant and tilt, with depth via binocular disparity. Through this method, we examined how STPp and VPS encode this information. Our results suggest that both regions encode the orientation and depth of 3D surfaces, with interactions among these parameters influencing neural responses. Additionally, we investigated how motion cues affect the perception of 3D surface orientation. STPp consistently encoded plane orientation information regardless of motion cue, whereas VPS responses showed less stability. These findings shed light on the distinct processing mechanisms for 3D spatial information in different cortical areas, offering insights into the neural basis of visual stability and spatial perception.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key points</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Both STPp and VPS can encode 3D surface orientation.</li>\u0000 \u0000 <li>Slant is encoded independently from tilt and disparity in STPp and VPS areas.</li>\u0000 \u0000 <li>TDD neurons shift their depth preferences based on tilt in STPp and VPS areas.</li>\u0000 \u0000 <li>STPp maintains stable 3D orientation encoding under motion conditions, while VPS shows less stability with changes in tilt and disparity preferences.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 6","pages":"1541-1566"},"PeriodicalIF":4.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}