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.

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Flexible control of motor units: is the multidimensionality of motor unit manifolds a sufficient condition?

  •  18 February 2025

Graphical Abstract

Dimensionality of motor unit behaviour Motor unit recruitment flexibility during sinusoidal tasks The online control task with visual feedback Simulation scenarios Flexible control of motor units: is the multidimensionality of motor unit manifolds a sufficient condition? Issue ,

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.

Open access

Mitochondrial control of ciliary gene expression and structure in striatal neurons

  •  18 February 2025

Graphical Abstract

Mitochondrial and ciliary pathways are associated in the D1-MSNs of the rat NAc The association between Mito/CiliaPathways is also present in mice D1-MSNs Mfn2 downregulation perturbs primary cilium structure Endogenous Mfn2 and rootletin levels correlate Rescuing cilium components does not lead to cell death following mitofusin 2 downregulation Mitochondrial control of ciliary gene expression and structure in striatal neurons Issue ,

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.

Open access

Modelling the time‐resolved modulations of cardiac activity in rats: A study on pharmacological autonomic stimulation

  •  18 February 2025

Graphical Abstract

Pipeline for the estimation of the fluctuating parameters of the Poincaré plot Estimation of the parameters kp${{{\bm{k}}}_{\bm{p}}}$ and ks${{{\bm{k}}}_{\bm{s}}}$ for the estimation of CSI and CPI in the SHR strain Cardiac autonomic indices CSI and CPI, and their spectral counterparts LF and HF under the rest to dobutamine transition Modelling the time-resolved modulations of cardiac activity in rats: A study on pharmacological autonomic stimulation Issue ,

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.

Open access

Determining properties of human‐induced pluripotent stem cell‐derived cardiomyocytes using spatially resolved electromechanical metrics

  •  17 February 2025

Graphical Abstract

Open-well cardiac microtissues (Samples C1–C6) Illustrations of the considered biomarkers. Illustration of components of the applied single-cell model. Illustrations of the cell geometry and possible cell connections in the spatial cell collection model Illustration of the seven chips (i.e. cell collections) C1–C7 considered in this study. More detailed illustration of the model cell distribution in Chip C2. Illustration of a slow electrical wave travelling through Chip C1. Illustration of (almost) synchronous cells in Chip C4. Measured and simulated voltage and displacement traces for the cells in Chip C4 in the baseline case and after the application of 0.1 µM of the L-type calcium channel blocker, nifedipine. Sensitivity of the biomarkers to changes in the biophysical parameters gKr$g_{\mathrm{Kr}}$, gNa$g_{\mathrm{Na}}$, gCaL$g_{\mathrm{CaL}}$, kRD$k_{RD}$, kDX$k_{DX}$, kXD$k_{XD}$, kPD$k_{PD}$ and Gi,j$G^{i,j}$. Flecainide. Flecainide. Flecainide. Quinidine. Nifedipine. Verapamil. Blebbistatin. Omecamtiv. Determining properties of human-induced pluripotent stem cell-derived cardiomyocytes using spatially resolved electromechanical metrics Issue ,

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.

Open access

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

Diagram of the exercise protocol Conceptual framework for mitochondrial outcome measurements Assessment of resting rates of oxidative ATP synthesis (ATPox, A), Mb-derived VO2 (B) and P/O ratio (C) Mean power output during dynamic constant-load plantar flexion exercises at 25, 50, 75, 100% of maximal work rate (WRmax) Changes in high-energy phosphate, intracellular pH and oxidative ATP (ATPox) synthesis rate Changes in MbO2 (A) and Mb-derived VO2 with respect to workload (B) and the linear relationship between ATPox synthesis rate and MbO2 (C) Mitochondrial efficiency in resting skeletal muscle in vivo: a novel non-invasive approach using multinuclear magnetic resonance spectroscopy in humans Issue ,

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.

Open access

Cerebral blood flow during simulated central hypovolaemia in people with hypertension: does vertebral artery hypoplasia matter?

  •  17 February 2025

Graphical Abstract

Basilar artery blood flow and conductance responses to LBNP Internal carotid artery blood flow and conductance responses to LBNP Total cerebral blood flow and conductance responses to LBNP Systemic haemodynamic responses to LBNP The end tidal CO2 response to LBNP The change in interbal carotid artery blood flow during LBNP Cerebral blood flow during simulated central hypovolaemia in people with hypertension: does vertebral artery hypoplasia matter? Issue ,

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

Three-dimensional plane orientation and experimental stimuli Reconstruction of recording sites in STPp and VPS Neural response example of STPp and VPS to three-dimensional plane stimuli Mean disparity tuning characteristics at different slant angles in STPp and VPS Tilt tuning characteristics at different slant angles in STPp and VPS TDD example neurons from areas STPp and VPS Population summary of response patterns for TDD neurons Comparative analysis of neural responses in STPp and VPS neurons under motion and non-motion conditions Comparative analysis of mean disparity and tilt-tuning characteristics in STPp and VPS under motion and non-motion conditions The visual representation of 3D orientation in macaque areas STPp and VPS Issue ,

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.

Open access

Early sensorimotor restriction in rats induces age‐dependent mitochondrial alterations in skeletal muscles and brain structures

  •  13 February 2025

Graphical Abstract

Soleus (SOL) and extensor digitorum longus (EDL) weight relative to body weight Effect of SMR on mitochondrial enzyme activities and mitochondrial respiration in skeletal muscles Evolution of mitochondrial enzyme activities in skeletal muscles Effect of SMR on mitochondrial enzyme activities and mitochondrial respiration in brain structures Evolution of mitochondrial enzyme activities in brain structures Early sensorimotor restriction in rats induces age-dependent mitochondrial alterations in skeletal muscles and brain structures Issue ,

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

Assessment of human CS input–output during goal-directed action preparation Modulation of CS input–output across goal-directed action preparation contexts Preparatory suppression during goal-directed action preparation Behavioural performance during non-stimulated (top) and stimulated (bottom) trials and its relationship to CS input–output gain modulation Modulation of CS input–output across participant sex and task order Theorized role of divisive normalization during goal-directed action preparation Goal-directed action preparation in humans entails a mixture of corticospinal neural computations Issue ,

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.

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Issue Information

  •  773-774
  •  13 February 2025
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