Personalized depth-specific neuromodulation of the human primary motor cortex via ultrasound
J Physiol. 2024 Feb 15. doi: 10.1113/JP285613. Online ahead of print.ABSTRACTNon-invasive brain stimulation has the potential to boost neuronal plasticity in the primary motor cortex (M1), but it remains unclear whether the stimulation of both superficial and deep layers of the human motor cortex can effectively promote M1 plasticity. Here, we leveraged transcranial ultrasound stimulation (TUS) to precisely target M1 circuits at depths of approximately 5 mm and 16 mm from the cortical surface. Initially, we generated computed tomography images from each participant's individual anatomical magnetic resonance images (MRI), w...
Source: The Journal of Physiology - February 15, 2024 Category: Physiology Authors: Shancheng Bao Hakjoo Kim Nandan B Shettigar Yue Li Yuming Lei Source Type: research

Rise and shine, it's exercising to improve metabolic syndrome time
J Physiol. 2024 Feb 15. doi: 10.1113/JP286068. Online ahead of print.NO ABSTRACTPMID:38358854 | DOI:10.1113/JP286068 (Source: The Journal of Physiology)
Source: The Journal of Physiology - February 15, 2024 Category: Physiology Authors: CeAnn C Udovich Source Type: research

Circulating noradrenaline leads to release of neuropeptide Y from cardiac sympathetic nerve terminals via activation of β-adrenergic receptors
In this study, fast-scan cyclic voltammetry and capacitive immunoprobes were used to allow for real-time in vivo measurements of interstitial myocardial neurotransmitters and neuropeptides, respectively. Using an in vivo porcine model with cardiac fast-scan cyclic voltammetry and capacitive immunoprobes, it was shown that systemic NA can increase ventricular interstitial NPY levels, suggesting that NA induces NPY release from postganglionic sympathetic nerves. The release of NPY was blocked by administration of the non-selective β-blocker propranolol, suggesting that release of NPY is dependent on activation of β-adrener...
Source: The Journal of Physiology - February 14, 2024 Category: Physiology Authors: Valerie Y H van Weperen Jonathan D Hoang Neil R Jani Artin Khaky Neil Herring Corey Smith Marmar Vaseghi Source Type: research

Inspiratory and sigh breathing rhythms depend on distinct cellular signalling mechanisms in the preB ötzinger complex
J Physiol. 2024 Feb 14. doi: 10.1113/JP285582. Online ahead of print.ABSTRACTBreathing behaviour involves the generation of normal breaths (eupnoea) on a timescale of seconds and sigh breaths on the order of minutes. Both rhythms emerge in tandem from a single brainstem site, but whether and how a single cell population can generate two disparate rhythms remains unclear. We posit that recurrent synaptic excitation in concert with synaptic depression and cellular refractoriness gives rise to the eupnoea rhythm, whereas an intracellular calcium oscillation that is slower by orders of magnitude gives rise to the sigh rhythm. ...
Source: The Journal of Physiology - February 14, 2024 Category: Physiology Authors: Daniel S Borrus Marco K Stettler Cameron J Grover Eva J Kalajian Jeffrey Gu Gregory D Conradi Smith Christopher A Del Negro Source Type: research

Cortical-brainstem circuitry attenuates physiological stress reactivity
J Physiol. 2024 Feb 14. doi: 10.1113/JP285627. Online ahead of print.ABSTRACTExposure to stressful stimuli promotes multi-system biological responses to restore homeostasis. Catecholaminergic neurons in the rostral ventrolateral medulla (RVLM) facilitate sympathetic activity and promote physiological adaptations, including glycaemic mobilization and corticosterone release. While it is unclear how brain regions involved in the cognitive appraisal of stress regulate RVLM neural activity, recent studies found that the rodent ventromedial prefrontal cortex (vmPFC) mediates stress appraisal and physiological stress responses. T...
Source: The Journal of Physiology - February 14, 2024 Category: Physiology Authors: Sebastian A Pace Ema Lukinic Tyler Wallace Carlie McCartney Brent Myers Source Type: research

Severe hypoxaemic hypercapnia compounds cerebral oxidative-nitrosative stress during extreme apnoea: Implications for cerebral bioenergetic function
We examined the extent to which apnoea-induced extremes of oxygen demand/carbon dioxide production impact redox regulation of cerebral bioenergetic function. Ten ultra-elite apnoeists (six men and four women) performed two maximal dry apnoeas preceded by normoxic normoventilation, resulting in severe end-apnoea hypoxaemic hypercapnia, and hyperoxic hyperventilation designed to ablate hypoxaemia, resulting in hyperoxaemic hypercapnia. Transcerebral exchange of ascorbate radicals (by electron paramagnetic resonance spectroscopy) and nitric oxide metabolites (by tri-iodide chemiluminescence) were calculated as the product of ...
Source: The Journal of Physiology - February 13, 2024 Category: Physiology Authors: Damian M Bailey Anthony R Bain Ryan L Hoiland Otto F Barak Ivan Drvis Benjamin S Stacey Angelo Iannetelli Gareth W Davison Rasmus H Dahl Ronan M G Berg David B MacLeod Zeljko Dujic Philip N Ainslie Source Type: research

Optogenetic confirmation of transverse-tubular membrane excitability in intact cardiac myocytes
J Physiol. 2024 Feb 13. doi: 10.1113/JP285202. Online ahead of print.ABSTRACTT-tubules (TT) form a complex network of sarcolemmal membrane invaginations, essential for well-co-ordinated excitation-contraction coupling (ECC) and thus homogeneous mechanical activation of cardiomyocytes. ECC is initiated by rapid depolarization of the sarcolemmal membrane. Whether TT membrane depolarization is active (local generation of action potentials; AP) or passive (following depolarization of the outer cell surface sarcolemma; SS) has not been experimentally validated in cardiomyocytes. Based on the assessment of ion flux pathways need...
Source: The Journal of Physiology - February 13, 2024 Category: Physiology Authors: Marina Scardigli Michal P ásek Lorenzo Santini Chiara Palandri Emilia Conti Claudia Crocini Marina Campione Leslie M Loew Antoine A F de Vries Dani ël A Pijnappels Francesco S Pavone Corrado Poggesi Elisabetta Cerbai Raffaele Coppini Peter Kohl Cecilia Source Type: research

Thermodynamic limitations on brain oxygen metabolism: physiological implications
J Physiol. 2024 Feb 13. doi: 10.1113/JP284358. Online ahead of print.ABSTRACTRecent thermodynamic modelling indicates that maintaining the brain tissue ratio of O2 to CO2 (abbreviated tissue O2 /CO2 ) is critical for preserving the entropy increase available from oxidative metabolism of glucose, with a fall of that available entropy leading to a reduction of the phosphorylation potential and impairment of brain energy metabolism. This provides a novel perspective for understanding physiological responses under different conditions in terms of preserving tissue O2 /CO2 . To enable estimation of tissue O2 /CO2 in the human b...
Source: The Journal of Physiology - February 13, 2024 Category: Physiology Authors: Richard B Buxton Source Type: research

Excitatory action of low frequency depolarizing GABA/glycine synaptic inputs is prevalent in prenatal spinal SOD1 < sup > G93A < /sup > motoneurons
J Physiol. 2024 Feb 12. doi: 10.1113/JP285105. Online ahead of print.ABSTRACTAmyotrophic lateral sclerosis (ALS) is a fatal adult-onset neurodegenerative disease characterized by progressive motor neuron degeneration and muscle paralysis. Recent evidence suggests the dysfunction of inhibitory signalling in ALS motor neurons. We have shown that embryonic day (E)17.5 spinal motoneurons (MNs) of the SOD1G93A mouse model of ALS exhibit an altered chloride homeostasis. At this prenatal stage, inhibition of spinal motoneurons (MNs) is mediated by depolarizing GABAergic/glycinergic postsynaptic potentials (dGPSPs). Here, using an...
Source: The Journal of Physiology - February 12, 2024 Category: Physiology Authors: Hongmei Zhu Urvashi Dalvi William Cazenave Daniel Cattaert Pascal Branchereau Source Type: research

Role of paraoxonase 3 in regulating ENaC-mediated Na < sup > + < /sup > transport in the distal nephron
We examined the physiological role of PON3 in renal Na+ and K+ handling using a Pon3 knockout (KO) mouse model. At baseline, Pon3 KO mice had lower blood [K+ ], more functional ENaC in connecting tubules/cortical collecting ducts, higher amiloride-induced natriuresis, and enhanced sodium chloride co-transporter (NCC) phosphorylation. Upon challenge with a high K+ diet, Pon3 KO mice had normalized blood [K+ ] and -NCC phosphorylation but lower circulating aldosterone levels compared to their littermate controls. Kidney PON3 abundance was altered in mice under dietary K+ loading or K+ restriction, providing a potential mecha...
Source: The Journal of Physiology - February 12, 2024 Category: Physiology Authors: Stephanie M Mutchler Sarah Christine M Whelan Allison Marciszyn Jingxin Chen Thomas R Kleyman Shujie Shi Source Type: research

Human sodium current voltage-dependence at physiological temperature measured by coupling a patch-clamp experiment to a mathematical model
In this study, we measured Na+ current voltage-dependence in stem cell-derived cardiomyocytes at physiological temperature. While the apparent activation and inactivation curves, measured as the dependence of current amplitude on voltage, fall within the range reported in previous studies, we identified a systematic error in our measurements. This error is caused by the deviation of the membrane potential from the command potential of the amplifier. We demonstrate that it is possible to account for this artifact using computer simulation of the patch-clamp experiment. We obtained surprising results through patch-clamp mode...
Source: The Journal of Physiology - February 12, 2024 Category: Physiology Authors: Veronika O Abrasheva Sandaara G Kovalenko Mihail Slotvitsky Serafima А Romanova Aleria A Aitova Sheida Frolova Valeria Tsvelaya Roman A Syunyaev Source Type: research

Reduced plakoglobin increases the risk of sodium current defects and atrial conduction abnormalities in response to androgenic anabolic steroid abuse
In this study, we observed a significantly higher proportion of males who had ARVC compared with females, and atrial arrhythmias and P wave changes represented a common observation in advanced ARVC stages. In mice with reduced plakoglobin expression, chronic administration of 5α-dihydrotestosterone led to P wave abnormalities, atrial conduction slowing, sodium current depletion and a decrease in membrane-localized NaV 1.5 clusters. 5α-Dihydrotestosterone, therefore, represents a stimulus aggravating the pro-arrhythmic phenotype in carriers of desmosomal mutations and can affect atrial electrical function.PMID:38345865 | ...
Source: The Journal of Physiology - February 12, 2024 Category: Physiology Authors: Laura C Sommerfeld Andrew P Holmes Ting Y Yu Christopher O'Shea Deirdre M Kavanagh Jeremy M Pike Thomas Wright Fahima Syeda Areej Aljehani Tania Kew Victor R Cardoso S Nashitha Kabir Claire Hepburn Priyanka R Menon Sophie Broadway-Stringer Molly O'Reilly Source Type: research

Role of tissue biomechanics in the formation and function of myocardial trabeculae in zebrafish embryos
J Physiol. 2024 Feb 12. doi: 10.1113/JP285490. Online ahead of print.ABSTRACTCardiac trabeculae are uneven ventricular muscular structures that develop during early embryonic heart development at the outer curvature of the ventricle. Their biomechanical function is not completely understood, and while their formation is known to be mechanosensitive, it is unclear whether ventricular tissue internal stresses play an important role in their formation. Here, we performed imaging and image-based cardiac biomechanics simulations on zebrafish embryonic ventricles to investigate these issues. Microscopy-based ventricular strain m...
Source: The Journal of Physiology - February 12, 2024 Category: Physiology Authors: Adriana Gaia Cairelli Alex Gendernalik Wei Xuan Chan Phuc Nguyen Julien Vermot Juhyun Lee David Bark Choon Hwai Yap Source Type: research

Inhibition and potentiation of the exercise pressor reflex by pharmacological modulation of TRPC6 in male rats
J Physiol. 2024 Feb 10. doi: 10.1113/JP286118. Online ahead of print.ABSTRACTWe determined the role played by the transient receptor potential canonical 6 (TRPC6) channel in evoking the mechanical component of the exercise pressor reflex in male decerebrated Sprague-Dawley rats. TRPC6 channels were identified by quadruple-labelled (DiI, TRPC6, neurofilament-200 and peripherin) immunohistochemistry in dorsal root ganglion (DRG) cells innervating the triceps surae muscles (n = 12). The exercise pressor reflex was evoked by statically contracting the triceps surae muscles before and after injection of the TRPC6 antagonist BI-...
Source: The Journal of Physiology - February 10, 2024 Category: Physiology Authors: Guillaume P Ducrocq Laura Anselmi Salvatore L Stella Steven W Copp Victor Ruiz-Velasco Marc P Kaufman Source Type: research

How neural networks walk and chew gum
J Physiol. 2024 Feb 10. doi: 10.1113/JP286287. Online ahead of print.NO ABSTRACTPMID:38340086 | DOI:10.1113/JP286287 (Source: The Journal of Physiology)
Source: The Journal of Physiology - February 10, 2024 Category: Physiology Authors: Nathan A Baertsch Ryan S Phillips Source Type: research