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The Journal of Physiology publishes research in all areas of physiology and pathophysiology that illustrates new physiological principles, mechanisms or premises. Papers on work at the molecular level, cell membrane, single cells, tissues or organs, and on systems physiology are all encouraged. We are particularly keen on research that has a clinical or translational focus, to help further our understanding of the role physiology plays in health and disease.
A publication of The Physiological Society
Featured in The Journal of Physiology
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Flexible control of motor units: is the multidimensionality of motor unit manifolds a sufficient condition?
-  18 February 2025
Graphical Abstract

Abstract figure legend We recorded large populations of motor units from the vastus lateralis (VL) and gastrocnemius medialis (GM). Using a linear dimensionality reduction approach, we observed that GM motor unit activity was effectively captured by a single latent factor, defining a unidimensional manifold. In contrast, VL motor units were better represented by three latent factors, defining a multidimensional manifold. We then evaluated the flexibility of motor unit control during sinusoidal contractions with torque feedback (torque control) and during online control tasks with visual feedback on firing rates (firing rate control). Flexibility was low regardless of the muscle. We propose that spinal circuits can shape supraspinal drive to generate multidimensional manifolds without necessarily providing additional capacity for volitional control. pps, pulses per second.
Mitochondrial control of ciliary gene expression and structure in striatal neurons
-  18 February 2025
Graphical Abstract

Abstract figure legend Neurons drive animal behaviour by receiving and transmitting information and require energy, primarily supplied by mitochondria, to function. Additionally, neurons need to sense environmental changes to adapt, a function that is locally played by the primary cilia. Using transcriptomic approaches and immunohistochemistry, we report a close molecular connection between mitochondria and cilia in the medium spiny neurons of the nucleus accumbens, showing that downregulation of the mitochondrial protein mitofusin 2 (Mfn2) by knockdown leads to alterations in ciliary transcriptomic footprint and structure.
Modelling the time‐resolved modulations of cardiac activity in rats: A study on pharmacological autonomic stimulation
-  18 February 2025
Graphical Abstract

Abstract figure legend Time-resolved estimation of cardiac rhythmicity parameters. A pipeline is shown for the estimation of the fluctuating cardiac parameters, based on the Poincaré plot. The Poincaré plot illustrates the successive changes in interbeat intervals (IBI). The parameters computation includes the distance from the ellipse centre to the origin (baseline cardiac cycle duration, CCD), as well as the minor (SD1) and major ratios (SD2), representing the short- and long-term cardiac rhythmicity changes within the defined time window.
Determining properties of human‐induced pluripotent stem cell‐derived cardiomyocytes using spatially resolved electromechanical metrics
-  17 February 2025
Graphical Abstract

Abstract figure legend In this study, we use human-induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) experiments and computational modelling to identify the mechanism of action of drug compounds. In the hiPSC-CM experiments, optical measurements of cell collections are recorded in the baseline case and after drug exposure. From these images, electromechanical biomarkers like action potential duration, beat rate, conduction velocity and mechanical displacement are evaluated. These biomarkers are then used to fit the biophysical parameters of a cell-based spatially resolved computational model of collections of hiPSC-CMs. Parameters are identified such that simulations of the parameterized computational model replicate the biomarkers observed in the experiments. The drug's mechanism of action in terms of alterations in ion channel function or cross-bridge cycle transitions is subsequently revealed by comparing the biophysical parameters in the baseline and drug-exposed cases.
Mitochondrial efficiency in resting skeletal muscle in vivo: a novel non-invasive approach using multinuclear magnetic resonance spectroscopy in humans
-  17 February 2025
Graphical Abstract

Abstract figure legend This graphical abstract illustrates our novel, non-invasive approach using combined 31P/1H magnetic resonance spectroscopy (MRS) to measure mitochondrial efficiency in resting human skeletal muscle in vivo. In this study, we quantified mitochondrial efficiency from the ATP synthesis rate and myoglobin-derived VO2 in the plantar flexor muscles of healthy adults under resting conditions and during graded exercise. Our result demonstrated a P/O ratio of 1.95 at rest, consistent with previous in vitro and in vivo methodologies. During exercise, this methodology led to non-physiological P/O ratios thus requiring further refinement.
Cerebral blood flow during simulated central hypovolaemia in people with hypertension: does vertebral artery hypoplasia matter?
-  17 February 2025
Graphical Abstract

Abstract figure legend Participants with hypertension underwent magnetic resonance angiography (MRA) during central hypovolaemia induced by lower body negative pressure (LBNP). Participants were assigned to a group with vertebral artery hypoplasia (VAH; n = 13) or without VAH group (n = 11) 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 ICA flow decreased during LBNP and was not different between groups. Total CBF and BA flow was decreased during LBNP in hypertensives without VAH but surprisingly was unchanged in patients with VAH. Blood pressure (BP) was reduced in the group without VAH only, whereas the rise in total peripheral resistance (TPR) was greater in the group with VAH. In summary, hypertensive patients without VAH may tolerate decreases in CBF, whereas patients with VAH evoke a greater systemic TPR response to preserve CBF.
The visual representation of 3D orientation in macaque areas STPp and VPS
-  13 February 2025
Graphical Abstract

Abstract figure legend Visual representation characteristic of 3D orientation in macaque areas STPp and VPS. The top panel shows visual areas with 3D surface representation, with illustrations of the dorsal (blue arrows) and ventral (green arrows) streams. The lower panels illustrate neuronal responses in macaque cortical areas STPp (purple box) and VPS (blue box) to 3D orientation stimuli. In the STPp (purple box): the left plot shows neuronal tuning to tilt (red) and mean disparity (blue), with different transparency levels reflecting varying Slant angles. The middle plot demonstrates that motion signals enhance firing rates without changing preferences for tilt or mean disparity (dashed lines: tuning curves under non-motion condition; continuous lines: tuning curves under motion condition). The right plot displays TDD neurons, where preferences for tilt and mean disparity shift interdependently (black and red lines: first and second response peaks). In the VPS (blue box): the left plot shows tuning to tilt (red) and mean disparity (blue). The middle plot reveals that motion signals enhance firing rates, alter tilt preferences and diminish mean disparity tuning. The right plot shows that TDD neurons in VPS exhibit interdependent response patterns similar to those in STPp.
Early sensorimotor restriction in rats induces age‐dependent mitochondrial alterations in skeletal muscles and brain structures
-  13 February 2025
Graphical Abstract

Abstract figure legend This study aimed to determine whether early sensorimotor restriction (SMR) alters mitochondrial enzyme activities in rat muscles and brain structures. SMR was induced via immobilizing the hind limbs of pups for 16 h per day during the dark phase from birth to postnatal day (PND) 28. Enzyme activities of citrate synthase (CS) and respiratory chain complexes I, II and IV were measured at two developmental stages (PND15 and PND28), using a spectrophotometric technique, in two hind limb muscles [soleus and extensor digitorum longus (EDL)] and four brain structures (sensorimotor cortex, striatum, prefrontal cortex and hippocampus) in control and SMR rats. Mitochondrial respiration was assessed at PND28 in muscles and brain structures (sensorimotor cortex, prefrontal cortex and hippocampus). Our results show that CS activity was transiently decreased in the slow-twitch soleus and increased in the sensorimotor cortex and striatum, conmprisng two brain structures involved in motor functions. Complex activities were decreased in EDL at PND15 only, in the soleus at both stages and in the hippocampus at PND28 only. The mitochondrial respiration driven by complex I or complexes I+II was reduced in the soleus and sensorimotor cortex. Mitochondrial enzyme activities are therefore sensitive to early SMR in skeletal muscles and brain structures involved in cognitive and motor processes.
Goal‐directed action preparation in humans entails a mixture of corticospinal neural computations
-  13 February 2025
Graphical Abstract

Abstract figure legend Goal-directed action preparation shapes corticospinal output across selected, non-selected and task-irrelevant motor representations. This study examined whether additive and multiplicative neural computations, common in sensory systems, occur within the corticospinal pathway during action preparation. We probed corticospinal input–output during the performance of various instructed-delay response tasks by applying a range of transcranial magnetic stimulation (TMS) intensities (input) over the primary motor cortex and measuring the resultant motor-evoked potentials (output) from the hand. We found that goal-directed action preparation increases corticospinal gain multiplicatively in task-relevant motor representations at the same time as additively suppressing non-selected and irrelevant representations. Greater gain modulation predicted faster responses, highlighting how these computations can enhance signal-to-noise (SNR) to enable efficient action selection and execution in the human motor system.
The impact of acute and chronic stress on gastrointestinal physiology and function: a microbiota–gut–brain axis perspective
- The Journal of Physiology
-  4491-4538
-  27 September 2023
Sex differences in human performance
- The Journal of Physiology
-  4129-4156
-  6 August 2024
The fourth dimension: physiological resilience as an independent determinant of endurance exercise performance
- The Journal of Physiology
-  4113-4128
-  22 August 2023
Low energy availability reduces myofibrillar and sarcoplasmic muscle protein synthesis in trained females
- The Journal of Physiology
-  3481-3497
-  16 June 2023
Muscle memory in humans: evidence for myonuclear permanence and long‐term transcriptional regulation after strength training
- The Journal of Physiology
-  4171-4193
-  19 August 2024
Efficacy of morning versus afternoon aerobic exercise training on reducing metabolic syndrome components: A randomized controlled trial
- The Journal of Physiology
-  6463-6477
-  28 November 2023
Morning exercise and pre‐breakfast metformin interact to reduce glycaemia in people with type 2 diabetes: a randomized crossover trial
- The Journal of Physiology
-  6491-6506
-  24 March 2024
Fast and sensitive GCaMP calcium indicators for neuronal imaging
- The Journal of Physiology
-  1595-1604
-  22 February 2023
Menstrual cycle phase does not influence muscle protein synthesis or whole‐body myofibrillar proteolysis in response to resistance exercise
- The Journal of Physiology
-  4 December 2024