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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Biogenesis and reformation of synaptic vesicles

  •  5 October 2024

Graphical Abstract

Axonal transport of precursor vesicles and presynapse assembly Mechanisms of SV reformation in mature neurons Biogenesis and reformation of synaptic vesicles Issue ,

Abstract figure legend Synaptic vesicle proteins are axonally transported in precursor vesicles (PVs) before conversion into mature synaptic vesicles (SVs) that are reformed by local recycling at synapses.

Physiological and behavioural implications of the portosystemic shunt in C57Bl/6J mice

  •  4 October 2024

Graphical Abstract

Study scheme Evidence for the portosystemic shunt (PSS) presence in C57Bl/6J mice Hippocampal metabolites in the brain of C57Bl/6J mice with and without the portosystemic shunt Body and organ weights in C57Bl/6J mice with and without the portosystemic shunt (PSS) at 52 weeks of age MR volumetry measurements in the brain of C57Bl/6J mice with and without the portosystemic shunt (PSS) Brain glucose utilisation in C57Bl/6J mice with and without the portosystemic shunt (PSS) Effect of the portosystemic shunt (PSS) on the spontaneous behaviour and fear memory in C57Bl/6J mice Alterations of posture and gait in portosystemic shunt (PSS) C57Bl/6J mice Pharmacokinetics of diazepam in C57Bl/6J mice with and without the portosystemic shunt (PSS) Physiological and behavioural implications of the portosystemic shunt in C57Bl/6J mice Issue ,

Abstract figure legend A significant fraction of inbred C57Bl/6J mice have congenital portosystemic shunt (PSS). We report PSS incidence in 9.2% of C57Bl/6J mice. PSS was detected directly by liver magnetic resonance angiography and brain 1H-magnetic resonance spectroscopy. Elevated plasma total bile acids indicated PSS presence with 100% accuracy. For cost-effective PSS screening, we propose using total bile acid detection by the Thio-NAD enzyme cycling method. Brain anatomy and function in mice with PSS: altered neurometabolite profile, higher brain weight and volume, enhanced brain glucose utilisation. Behavioural changes in mice with PSS: hyperlocomotion, enhanced balance, altered gait, attenuated fear memory. Mice with PSS have altered internal organ weights, blood cell counts and blood clinical chemistry. PSS significantly distorts diazepam pharmacokinetics. Conclusion: in line with the principles of 3Rs, we recommend screening C57Bl/6J mouse cohorts for PSS presence as a significant refinement of any experiments involving this popular inbred strain.

Ubiquitin ligase signalling networks shape presynaptic development, function and disease

  •  3 October 2024

Graphical Abstract

Siah1 and Parkin drive presynaptic autophagy, synaptic vesicle dynamics and endosomal sorting Ube3A and Ube3B regulate presynaptic pruning and function Thin, HERC1 and Ariadne-1 in presynaptic excitatory transmission, synaptic vesicle dynamics and homeostatic plasticity Nedd4 in presynaptic metabotropic glutamate receptor trafficking MYCBP2 influences autophagy, acetyltransferases, microtubule stability and NMNAT LNX1/2 and HUWE1 regulate presynaptic function in glycinergic and GABAergic inhibitory neurons A network of ubiquitin ligases controls several presynaptic processes to influence synapse development, maintenance and function Ubiquitin ligase signalling networks shape presynaptic development, function and disease Issue ,

Abstract figure legend Depicted is the ubiquitin ligase network that positively (arrows) and negatively (bars) affects different processes that influence presynaptic development and function.

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The yellow brick road to understanding the RyR2 signalosome

  •  2 October 2024
No abstract is available for this article.
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Neurocardiology: translational advancements and potential

  •  27 September 2024

Graphical Abstract

Network interactions occurring within and between peripheral ganglia and the central nervous system for autonomic control of the heart Key structures of the central autonomic network Neurocardiology is based on the premise that cardiac control must be evaluated in the context of the end-organ substrate and interdependent interactions within multiple levels of the cardiac nervous system Neurocardiology: translational advancements and potential Issue ,

Abstract figure legend Afferent signalling pathways of the autonomic nervous system and their efferent targets in the heart, kidneys and vasculature.

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Changes in intra‐ and interlimb reflexes from forelimb cutaneous afferents after staggered thoracic lateral hemisections during locomotion in cats

  •  27 September 2024

Graphical Abstract

Experimental chronology and estimation of lesion extent Phase-dependent modulation of cutaneous reflexes evoked in homonymous forelimb muscles during locomotion before and following staggered hemisections Phase-dependent modulation of cutaneous reflexes evoked in crossed forelimb muscles during locomotion before and following staggered hemisections Phase-dependent modulation of cutaneous reflexes evoked in homolateral hindlimb muscles during locomotion before and following staggered hemisections Phase-dependent modulation of cutaneous reflexes evoked in diagonal hindlimb muscles during locomotion before and following staggered hemisections Reflex response occurrence in all four limbs before and after staggered hemisections Schematic illustration of putative pathways and mechanisms contributing to cutaneous reflexes and their modulation before and after staggered hemisections Homolateral responses in the left soleus for one cat for grouped and separated forelimb cycles Changes in intra- and interlimb reflexes from forelimb cutaneous afferents after staggered thoracic lateral hemisections during locomotion in cats Issue ,

Abstract figure legend Contacting an obstacle during locomotion activates cutaneous afferents to maintain balance and co-ordinate all four limbs. Spinal cord injury (SCI) disrupts neural communications between spinal networks controlling the fore- and hindlimbs, impairing balance and limb co-ordination. Cutaneous reflex pathways can be used to develop therapeutic approaches for restoring ascending and descending transmission to facilitate locomotor recovery.

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