Journal of Physiology-London最新文献

{"title":"Heartfelt intervention: A role for PVN oxytocin neurons in the prediabetic heart.","authors":"Grace K Nielsen, Reesa M Wilcox, Han-Jun Wang","doi":"10.1113/JP289973","DOIUrl":"https://doi.org/10.1113/JP289973","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182334","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 adaptive and late degenerative tendon response to overload in rat model of synergist ablation.","authors":"Lily M Lin, Rita de Cassia Marqueti, Hailey M Bonelli, Justin Parreno, Karin Gravare Silbernagel, Dawn M Elliott","doi":"10.1113/JP289173","DOIUrl":"https://doi.org/10.1113/JP289173","url":null,"abstract":"<p><p>Mechanical loading is essential for tendon homeostasis. Increases in the duration and magnitude of load can promote tendon adaptation; however, excessive or prolonged overloading can surpass the tendon's adaptive capacity, leading to pathological degeneration. While the adaptive and degenerative responses of tendons to mechanical loading are well accepted, the threshold and mechanisms that distinguish adaptation from degeneration remain unknown. This study evaluated longitudinal mechanical, structural and cellular responses due to plantaris tendon overload using the synergistic ablation model (SynAb). Female Long-Evans rats either received bilateral SynAb surgery (Achilles tendon resected), or bilateral sham surgery, or were age-matched intact control. Animal activity was measured before surgery and then bi-weekly. Rats were euthanized at either 3 days, 8 weeks, or 16 weeks post-intervention. Each leg was randomly assigned for mechanical tests, histology, or gene expression. A subset of legs was also assessed for 3D tissue structure using magnetic resonance imaging. We observed time-dependent mechanical, structural, and cellular responses. While overload initially induced adaptive remodelling evidenced by increased tendon cross-sectional area and ultimate load, prolonged overload led to degenerative changes, including reduced mechanical properties (modulus and ultimate stress) and a transcriptomic profile showing elevated inflammatory and matrix degradation markers. These findings suggest that between 8 and 16 weeks, an adaptive-to-degenerative threshold was crossed, where repair mechanisms could no longer keep up with accumulated overload, triggering extracellular matrix breakdown. KEY POINTS: Mechanical loading is essential for tendon homeostasis and adaptive remodelling. However prolonged overload can lead to degeneration. The mechanisms driving adaptive remodelling or pathological degeneration in response to mechanical loading remain unknown. This study evaluated the longitudinal response to plantaris tendon overload using the synergist ablation model (SynAb). We observed time-dependent mechanical, structural and cellular changes to overload. Overload initially produced an adaptive response; however, prolonged overload eventually led to degeneration. These findings highlight a critical transition from adaptation to degeneration, opening important new opportunities to investigate mechanisms driving this progression. Understanding early changes is essential for identifying key factors that determine whether tendons adapt or develop pathology in response to increased loading.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182295","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":"Reduced osmoresponsiveness in magnocellular neuroendocrine neurones during chronic salt-loading.","authors":"Maja Lozic, Roongrit Klinjampa, Nancy Sabatier, Duncan J MacGregor, Gareth Leng, Mike Ludwig","doi":"10.1113/JP288860","DOIUrl":"https://doi.org/10.1113/JP288860","url":null,"abstract":"<p><p>Here, we studied the effects of salt-loading in rats on the electrophysiological behaviour of neurones that secrete oxytocin and vasopressin. After 7 days of salt-loading, the basal firing rate of both vasopressin cells and oxytocin cells in urethane-anaesthetized rats was increased by less than 1 spike s^-1, which is much less than expected from the hyperosmolality induced by saltloading. The neuronal responsiveness to acute osmotic stimuli was also markedly impaired, with no change in their responses to non-osmotic stimuli. We then undertook a systematic search of the literature for studies in salt-loaded rats that had measured oxytocin or vasopressin secretion, plasma osmolality, haematocrit or pituitary hormone content, and reviewed them in light of our electrophysiological findings. The prevailing understanding is that salt loading induces plastic changes in neuronal behaviour to promote exaggerated vasopressin secretion, but the conclusions that we draw from our electrophysiological findings in urethane-anaesthetized rats and the literature review suggest the converse - that vasopressin neurones selectively habituate to osmotic stimuli, presumably to conserve diminished pituitary stores of vasopressin while sustaining enough secretion for maximal renal effects. KEY POINTS: Seven days of 'salt-loading' produces a large increase in plasma osmolality and depletes the pituitary content of vasopressin and oxytocin, apparently reflecting enhanced secretion. Using in vivo electrophysiological recordings in urethane-anaesthetized rats, we show that, after 7 days of salt loading, the basal firing rate of both vasopressin and oxytocin cells was increased to a much lesser extent than expected from the hyperosmolality induced by acute osmotic stimuli. The neuronal responsiveness to acute osmotic stimuli was also markedly impaired with no change in their responses to non-osmotic stimuli. Our results show that these neurones strongly and selectively habituate to chronic osmotic stimuli, presumably to conserve diminished pituitary stores of hormone. Our conclusions contradict the prevailing understanding that salt loading promotes an exaggerated hyperexcitability of the hypothalamo-neurohypophysial system.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182314","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":"On the right track: navigating hormonal crossroads in female neuromuscular ageing.","authors":"Pádraig Spillane, Sophia T Jenz, Mollie O'Hanlon, Elisa Nédélec","doi":"10.1113/JP289271","DOIUrl":"https://doi.org/10.1113/JP289271","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182286","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":"Elevated carotid body tonic activity contributes to ventilatory acclimatization and de-acclimatization to high altitude at rest and during exercise.","authors":"Ayechew A Getu, L Madden Brewster, Travis D Gibbons, James D Anholm, Michael Stembridge, Philip N Ainslie, Jay M J R Carr","doi":"10.1113/JP289355","DOIUrl":"https://doi.org/10.1113/JP289355","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Exposure to hypoxia is associated with increased ventilation, which escalates with continued exposure. Carotid chemoreceptors play a critical role in ventilatory acclimatization to prolonged hypoxia in animals. However, the contribution of carotid chemoreceptor tonic activity to ventilatory acclimatization in humans has not been directly demonstrated. We assessed carotid chemoreceptor tonic activity in lowlanders following acclimatization to high altitude and during de-acclimatization. Fourteen healthy participants (7 male, 27 ± 4 years) were assessed at 340 m, following 13 days at high altitude (3800 m), and 3 days post-descent to 1200 m. Carotid chemoreceptor tonic activity was indexed by the two-breath nadir in minute ventilation ( &lt;math&gt; &lt;semantics&gt; &lt;msub&gt;&lt;mover&gt;&lt;mi&gt;V&lt;/mi&gt; &lt;mo&gt;̇&lt;/mo&gt;&lt;/mover&gt; &lt;mi&gt;E&lt;/mi&gt;&lt;/msub&gt; &lt;annotation&gt;$dot V_{mathrm{E}}$&lt;/annotation&gt;&lt;/semantics&gt; &lt;/math&gt; ) during 1 min of hyperoxia (100% inspired O&lt;sub&gt;2&lt;/sub&gt;), at rest and during cycling exercise, matched for relative intensity [∼50% maximal oxygen consumption ( &lt;math&gt; &lt;semantics&gt; &lt;msub&gt;&lt;mover&gt;&lt;mi&gt;V&lt;/mi&gt; &lt;mo&gt;̇&lt;/mo&gt;&lt;/mover&gt; &lt;mrow&gt;&lt;msub&gt;&lt;mi&gt;O&lt;/mi&gt; &lt;mn&gt;2&lt;/mn&gt;&lt;/msub&gt; &lt;mi&gt;max&lt;/mi&gt;&lt;/mrow&gt; &lt;/msub&gt; &lt;annotation&gt;${dot V_{{{mathrm{O}}_2}{mathrm{max}}}}$&lt;/annotation&gt;&lt;/semantics&gt; &lt;/math&gt; )] and absolute intensity (∼90 W). Resting &lt;math&gt; &lt;semantics&gt; &lt;msub&gt;&lt;mover&gt;&lt;mi&gt;V&lt;/mi&gt; &lt;mo&gt;̇&lt;/mo&gt;&lt;/mover&gt; &lt;mi&gt;E&lt;/mi&gt;&lt;/msub&gt; &lt;annotation&gt;$dot V_{mathrm{E}}$&lt;/annotation&gt;&lt;/semantics&gt; &lt;/math&gt; increased from sea level (12.9 ± 2.3 l/min) to 3800 m (16.8 ± 3.6 l/min, P &lt; 0.001) and 3-days post-descent (18.2 ± 3.5 l/min, P &lt; 0.001), with no difference between high altitude and post-descent (P = 0.366). The hyperoxic nadir in ventilation was greater than sea level at 3800 m (+153%; P = 0.070, Cohen's d = 1.3) and 3-days post-descent (+74%; P = 0.048), with no significant difference between 3800 m and post-descent (P = 0.326). During 50% &lt;math&gt; &lt;semantics&gt; &lt;msub&gt;&lt;mover&gt;&lt;mi&gt;V&lt;/mi&gt; &lt;mo&gt;̇&lt;/mo&gt;&lt;/mover&gt; &lt;mrow&gt;&lt;msub&gt;&lt;mi&gt;O&lt;/mi&gt; &lt;mn&gt;2&lt;/mn&gt;&lt;/msub&gt; &lt;mi&gt;max&lt;/mi&gt;&lt;/mrow&gt; &lt;/msub&gt; &lt;annotation&gt;${dot V_{{{mathrm{O}}_2}{mathrm{max}}}}$&lt;/annotation&gt;&lt;/semantics&gt; &lt;/math&gt; exercise, the hyperoxic ventilation nadir was also greater than sea level at 3800 m (+225%; P = 0.007) and 3 days post-descent (+183%; P = 0.004). The degree of ventilatory acclimatization was associated with the change in the hyperoxic nadir in ventilation (as an index of carotid chemoreceptor tonic activity; r&lt;sup&gt;2 = &lt;/sup&gt;0.60, P = 0.014). In conclusion, carotid chemoreceptor tonic activity is elevated and associated with acclimatization to high altitude, and this persists 3 days post-descent. KEY POINTS: Ascent to high altitude is associated with adjustments in ventilation (i.e. ventilatory acclimatization). Heightened carotid chemoreceptor activity plays a critical role in ventilatory acclimatization to prolonged hypoxia in animals; However, there have been no studies in humans directly assessing the contribution of carotid body tonic activity in ventila","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182319","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":"Adeno-associated virus-based rescue of Myo7a expression restores hair-cell function and improves hearing thresholds in a USH1B mouse strain.","authors":"Ana E Amariutei, Samuel Webb, Adam J Carlton, Andrew O'Connor, Anna Underhill, Jing-Yi Jeng, Sarah A Hool, Alice Zanella, Matthew Hool, Marie-José Lecomte, Stuart L Johnson, Saaid Safieddine, Walter Marcotti","doi":"10.1113/JP289526","DOIUrl":"https://doi.org/10.1113/JP289526","url":null,"abstract":"<p><p>Mutations in MYO7A, the gene encoding the unconventional myosin 7a, cause hereditary deafness in mice and humans. In the cochlea, MYO7A is present in the sensory hair cells from embryonic stages of development, and plays a critical role in the development and maintenance of the mechanosensitive hair bundles composed of actin-rich stereocilia. Shaker-1 mutant mice (Myo7a^Sh1/Sh1), the murine model of Usher 1B syndrome, exhibit a progressive loss of the stereocilia, subsequent degeneration of the sensory epithelium and ultimately profound deafness. In addition to the hair bundle defects, we found that the shaker-1 mutation prevented both inner hair cells (IHCs) and outer hair cells (OHCs) from acquiring their fully mature basolateral current profile. Delivering exogenous Myo7a to newborn Myo7a^Sh1/Sh1 mice using dual-adeno-associated virus 8 (AAV8)-Myo7a or dual-AAV9-PhP.eB-Myo7a, which primarily target IHCs, led to a substantial rescue of their hair bundle structure. The rescued bundles regained their ability to generate mechanoelectrical transducer (MET) currents in response to fluid jet displacement. Although the average MET current was smaller than in control IHCs, the normal resting open probability of the MET channel was fully restored. The IHCs of the treated cochlea also regained a mature basolateral membrane current profile. Functionally, rescue of the IHC structure and function, but not that of OHCs, leads to an average improvement of 20-30 dB in hearing thresholds across most frequencies. These results support dual AAV-induced gene replacement therapy as an effective strategy to recover hair-cell function in Myo7a^Sh1/Sh1 mice. KEY POINTS: Shaker-1 mutant mice (Myo7a^Sh1/Sh1), which carry a mutation in the unconventional myosin MYO7A and are the murine model of Usher 1B syndrome, become profoundly deaf at 1 month of age or soon after. In the mammalian cochlea, MYO7A is expressed in the hair cells, including within their actin-rich stereociliary bundles. We show that hair cells of Myo7a^Sh1/Sh1 mice progressively lose their transducing stereocilia and mechanoelectrical transduction, and fail to acquire their fully mature basolateral current profile. Delivering exogenous Myo7a to newborn Myo7a^Sh1/Sh1 mice using dual-adeno-associated virus (AAVs) led to a substantial rescue of the bundle structure and function of inner hair cells, including mechanoelectrical transduction. This functional rescue led to a 20-30 dB improvement in hearing thresholds across most frequencies. These results support dual AAV-induced gene replacement therapy as an effective strategy to recover the hair-cell function in Myo7a^Sh1/Sh1mice.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182303","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":"'Mini analysis' misrepresents changes in synaptic properties due to incomplete event detection.","authors":"Ingo H Greger, Jake F Watson","doi":"10.1113/JP288183","DOIUrl":"https://doi.org/10.1113/JP288183","url":null,"abstract":"<p><p>Patch-clamp recording of miniature postsynaptic currents (mPSCs, or 'minis') is used extensively to investigate the functional properties of synapses. With this approach, spontaneous synaptic transmission events are recorded in an attempt to determine quantal synaptic parameters or the effect of synaptic manipulations. However, at the majority of brain synapses these events are small, with many undetectable due to recording noise. The effects of incomplete detection were well appreciated in the early years of synaptic physiology analysis, but appear to be increasingly forgotten. Here we sought to characterise the consequences of incomplete detection on the interpretability of mini analysis, using simulated mPSC data to give full control over event parameters. We demonstrate that commonly reported measures such as mean event amplitude and frequency, are misrepresented by the loss of undetected events. Probabilistic loss of small events results in detected event amplitude distributions that appear biologically complete, yet do not reflect the underlying synaptic properties. With both simulated and experimental datasets, we demonstrate that specific changes in event amplitude are primarily detected as changes in frequency, compromising classical biological interpretations. To facilitate more robust data analysis and interpretation, we detail a means for experimental estimation of the event detection limit and provide practical recommendations for data analysis. Together, our study highlights how mini analysis is prone to falsely reporting synaptic changes, raising awareness of these considerations, and provides a framework for more robust data analysis and interpretation. KEY POINTS: 'Mini analysis' (patch-clamp recording of miniature synaptic currents, mPSCs) is widely used to assess synaptic function, relying on detection of spontaneous synaptic events. Detection of mPSC events is almost inevitably incomplete, as event amplitudes are close to the level of recording noise - a limitation that was well recognised in earlier literature but is often overlooked today. Using in silico simulated datasets, this study characterises how incomplete detection distorts reported parameters and the distributions of detected events. These effects can routinely compromise biological interpretation of mPSC data, particularly the interpretation of amplitude and frequency changes. We present a method for experimental estimation of the detection limit and make practical recommendations for maximally careful interpretation of mini data.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182296","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":"Unveiling sex dimorphism in the healthy cardiac anatomy: Fundamental differences between male and female heart shapes.","authors":"Beatrice Moscoloni, Cameron Beeche, Julio A Chirinos, Patrick Segers, Mathias Peirlinck","doi":"10.1113/JP288667","DOIUrl":"https://doi.org/10.1113/JP288667","url":null,"abstract":"<p><p>Sex-based differences in cardiovascular disease are well documented, yet the precise nature and extent of these discrepancies in cardiac anatomy remain incompletely understood. Traditional scaling models often fail to capture the interplay of age, blood pressure and body size, prompting a more nuanced investigation. Here we use statistical shape modelling in a healthy subset (n = 456) of the UK Biobank to explore sex-specific variations in biventricular anatomy. We reconstruct 3D meshes and perform multivariate analyses of shape coefficients, controlling for age, blood pressure and various body size metrics. Our findings reveal that sex alone explains at least 25% of morphological variability, with strong discrimination between men and women (AUC = 0.96-0.71) persisting even after correction for confounders. Notably, the most discriminative modes highlight pronounced differences in cardiac chamber volumes, the anterior-posterior width of the right ventricle and the relative positioning of the cardiac chambers. These results underscore that sex has a fundamental influence on cardiac morphology, which may have important clinical implications for differing cardiac structural assessments in men and women. Future work should investigate how these anatomical differences manifest in various cardiovascular conditions, ultimately paving the way for more precise risk stratification and personalised therapeutic strategies for both men and women. KEY POINTS: Men's and women's hearts differ significantly in overall shape and size, but an in-depth quantification of these sex differences in healthy cardiac anatomy is lacking. We used a three-dimensional statistical shape modelling approach that goes beyond standard clinical measurements to capture subtle anatomical features. Our findings show that sex alone accounts for at least 25% of the natural variation in heart structure, even after correcting for age, blood pressure and various body size metric confounders. Female hearts consistently present smaller chambers and different inter-chamber positioning compared with male hearts. Our findings highlight the importance of sex-specific anatomical insights for better diagnosis, treatment and research on heart disease.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151555","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":"Default mode and motor networks facilitate early learning of implicit motor sequences: a multimodal MR spectroscopy and fMRI study.","authors":"Joshua Hendrikse, Emily Brooks, Sarah Wallis, Dylan Curtin, Nigel C Rogasch, Murat Yücel, Mana Biabani, Charlotte J Stagg, Mark Bellgrove, Richard McIntyre, Chao Suo, James Coxon","doi":"10.1113/JP288361","DOIUrl":"https://doi.org/10.1113/JP288361","url":null,"abstract":"<p><p>Learning new motor skills is a fundamental process that involves the sequencing of actions. Skill develops with practice and time and manifests as performance that is fast and accurate. Although we know that learning can occur through an implicit process in the absence of conscious awareness, and across multiple temporal scales, the precise neural mechanisms mediating implicit motor sequence learning remain poorly understood. Similarly the capacity for interventions with known influence on learning and memory, such as cardiovascular exercise, to facilitate implicit learning is yet to be clearly established. Here we investigated the neuroplasticity of implicit motor sequence learning and the effect of acute exercise priming. Healthy adults (39.5% female) aged 22.55 ± 2.69 years were allocated to either a high-intensity interval training (HIIT) exercise group (n = 16) or to a very low-intensity control group (n = 17). After exercise participants performed a serial reaction time task, magnetic resonance (MR) spectroscopy estimates of sensorimotor GABA were acquired before and after exercise and during task performance, and resting-state functional magnetic resonance imaging (fMRI) was acquired at the end of the protocol. We show that early stages of learning are linked to default mode network connectivity, whereas the overall degree of learning following sustained practice is associated with motor network connectivity. Sensorimotor GABA concentration was linked to the early stages of learning, and GABA concentration was modulated following HIIT, although the two were not related. Overall through the integration of multiple neuroimaging modalities we demonstrate that interactions between hippocampal and motor networks underlie implicit motor sequence learning. KEY POINTS: Motor learning occurs across different temporal scales and can arise implicitly in the absence of conscious awareness. Explicit motor learning is linked to the brain's primary inhibitory neurotransmitter, GABA and interactions across motor and hippocampal networks. Whether these same neural mechanisms are implicated in implicit learning is unclear. Similarly the capacity to influence implicit learning via priming with cardiovascular exercise is yet to be clearly established. We show that early implicit learning is underpinned by default mode network connectivity and sensorimotor GABA concentration, whereas total learning following sustained practice is linked to motor network connectivity. We also found that high-intensity interval training (HIIT) exercise elevated sensorimotor GABA concentration, but not the magnitude of implicit learning. Overall our results highlight shared involvement of default mode and motor networks in implicit motor sequence learning.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132448","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":"From dropping to falling: Nocturnal blood pressure decline and fall risk in older adults","authors":"Audrey P. Stegman,&nbsp;Christopher M. Depner","doi":"10.1113/JP289779","DOIUrl":"10.1113/JP289779","url":null,"abstract":"&lt;p&gt;About one in three older adults experience falls, especially at night, representing a significant contributor to morbidity and mortality (McMahon et al., &lt;span&gt;2012&lt;/span&gt;). One mechanism potentially contributing to risk of such falls is an impaired blood pressure (BP) response to standing, where decreased BP after standing up leads to a loss of balance. Intriguingly, data from controlled tilt-table tests show the circadian system regulates BP responses to postural changes (Hu et al., &lt;span&gt;2011&lt;/span&gt;). This raises the hypothesis that the circadian clock, which controls 24 h rhythms in physiology, may influence BP responses to standing and, in turn, affect night-time fall risk in older adults. However, BP responses to standing after awakening from sleep have not been systematically studied, especially during the night. This knowledge contributes to the lack of effective evidence-based interventions to mitigate night-time fall risk among older adults.&lt;/p&gt;&lt;p&gt;For example, interventions will probably differ if fall risk is modulated by the circadian clock &lt;i&gt;vs&lt;/i&gt;. environmentally or behaviourally driven rhythms that typically occur at night, such as fasting, being sedentary and medication use, or an interaction among these factors (Klerman et al., &lt;span&gt;2022&lt;/span&gt;). Disentangling the potential influence of the circadian clock &lt;i&gt;vs&lt;/i&gt;. environmental/behavioural rhythms requires carefully designed circadian protocols such as the constant routine or forced-desynchrony. In general, these protocols eliminate or evenly distribute factors that can mask or influence the circadian clock, meaning that any detected physiological rhythms are strongly influenced by the circadian clock (Klerman et al., &lt;span&gt;2022&lt;/span&gt;).&lt;/p&gt;&lt;p&gt;Thus, to help define the contribution of the circadian clock to BP responses, and potentially fall risk in older adults, Thosar &amp; Shea (&lt;span&gt;2025&lt;/span&gt;) conducted a secondary analysis of a forced-desynchrony protocol where they quantified BP responses to standing across all circadian phases. The protocol used 10 ultra-short sleep-wake cycles of 5 h 20 min (2 h 40 min each of scheduled wakefulness and sleep per cycle), lasting 5 days. Participants consisted of two groups, midlife (&lt;i&gt;n&lt;/i&gt; = 19; aged 40–59 years) and older age (&lt;i&gt;n&lt;/i&gt; = 6; aged 60–70 years). Analyses quantified heart rate (HR), systolic BP and diastolic BP at 1 and 3 min in response to standing slowly from a supine position, 24 min into each waking episode. Key results showed the 1 min systolic BP response to standing was stable across all circadian phases in the midlife group, whereas the older group showed significantly depressed systolic BP at 1 min after standing, indicating an impaired BP response. Visually, Thosar &amp; Shea (&lt;span&gt;2025&lt;/span&gt;) identified the circadian biological night as the time of day with greatest impairment in the older group. Individual data plots show some variability in this impairment across participants in the midlife and old","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 19","pages":"5247-5248"},"PeriodicalIF":4.4,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://physoc.onlinelibrary.wiley.com/doi/epdf/10.1113/JP289779","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132504","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}