Celebrating Physiology in London, Summer 2026

Synaptic signaling in the human hippocampal CA3 network

Synaptic signaling in the human hippocampal CA3 network

The hippocampal CA3 network is the largest autoassociative network in the mammalian brain. CA3 pyramidal neurons are connected to each other through recurrent synapses endowed with Hebbian synaptic plasticity, forming an almost infinitely large synaptic matrix for storage and retrieval of information. In humans, the number of CA3 pyramidal neurons is 1.7 million, more than an order of magnitude higher than in mice (110,000). How this huge difference in cell numbers impacts on synaptic function and connectivity remains unclear.

To address this question, we applied cutting-edge electrophysiology and superresolution-expansion microscopy to slices from the human hippocampus. Recordings were focused on tissue from MRI-negative patients (“nonsclerotic”), in which cellular organization was largely preserved. Neuronal density in the CA3 region in MRI-negative patients was similar to that of postmortem tissue, further suggesting that the circuit may approach the physiological situation. We first characterized the CA3 network by multicellular patch clamp-based circuit mapping, and found that the recurrent CA3–CA3 synapse was characterized by high reliability and sparse connectivity. The average connectivity was 1.27%, substantially lower than in mice. To investigate the determinants of connectivity, we analyzed the number of spines in CA3 pyramidal neurons dedicated to the recurrent collateral inputs using superresolution-expansion microscopy. In humans, CA3 pyramidal cells had 16,100 spines, only moderately higher than in mice (13,200). Thus, our results indicate that cell number is the main determinant of connectivity, and suggest an inverse scaling rule between connectivity and cell number across species.

We next characterized the mossy fiber input by paired recordings between mossy fiber terminals and CA3 pyramidal neurons. Presynaptic mossy fiber terminals were stimulated in the non-invasive bouton-attached configuration. We found that stimulation of single stimuli in presynaptic terminals reliably triggered spiking in postsynaptic CA3 pyramidal neurons, demonstrating that the human mossy fiber synapse acts as a “detonator”. To assess connectivity, we estimated the number of large terminals impinging on the apical dendrites of CA3 pyramidal neurons using superresolution-expansion microscopy. In humans, single CA3 pyramidal neurons received inputs from 280 mossy fiber terminals, ~fivefold more than in mice (~50). Although the number of inputs per cell is higher, the total granule cell-to-CA3 pyramidal neuron connectivity is lower in humans. While the higher number of mossy fiber inputs per cell may enhance combinatorial coding, the sparse connectivity may facilitate pattern separation.

Taken together, our results show that both CA3–CA3 recurrent collateral synapses and mossy fiber synapses on CA3 pyramidal neurons follow complex evolutionary scaling rules, which may enhance the computational power of the human brain.

Presynaptic ultrastructure and vesicle mobility at cerebellar and hippocampal mossy fibre boutons support their functional divergence

Introduction. In vivo, cerebellar mossy fibre boutons (cMFBs) can sustain high-frequency transmission which is well-suited for rate coded signalling, while hippocampal mossy fibre boutons (hMFBs) exhibit strong facilitation which is well-suited for burst coding. Despite sharing a common name and gross morphological features, it is unclear whether differences in presynaptic ultrastructure contributes to their distinct functional properties.

Aims. We compared the presynaptic ultrastructure and vesicle mobility in cMFBs and hMFBs to determine whether they contribute to the different vesicle supply rates required for sustained rate and burst signalling in these axons.

Methods. Boutons from wild type mouse cerebellar and hippocampal tissue were analysed by transmission electron microscopy and electron tomography. Mitochondrial size and area fraction, active zone (AZ) surface area, and vesicle size and density were quantified stereologically [1]. Vesicle mobility was measured in acute slices from VGLUT1-Venus mice using fluorescence recovery after photobleaching (FRAP; 35°C) [2]. Biologically constrained 3D Monte Carlo simulations were used to model FRAP data and to predict sustained vesicle supply to multiple AZs.

Results. Mitochondria in cMFBs were larger (short-axis diameter: 243.8 ± 5.7 nm, n = 36 images) than in hMFBs (191.2 ± 3.0 nm, n = 26; p < 0.001, t-test) and more densely packed (area fraction: 0.224 ± 0.012 vs 0.076 ± 0.005; p < 0.001). AZs were significantly smaller in cMFBs (0.040 ± 0.006 µm², n = 8 AZs) than hMFBs (0.110 ± 0.026 µm², n = 8, p = 0.03, t-test), with lower docked vesicle density (102.4 ± 8.0, n = 20 vs 160.3 ± 10.6 vesicles/µm², n = 20, p < 0.001). Vesicle diameters were larger (45.4 ± 0.5 nm, n = 41 VOIs vs 44.0 ± 0.2 nm, n = 31, p = 0.007, t-test) and more variable in cMFBs, while vesicle cluster volume fraction was lower (0.340 ± 0.015 vs 0.418 ± 0.007; p < 0.001, t-test). FRAP revealed a 9-fold slower long-time diffusion coefficient in hMFBs (D_long = 2.7 ± 1.1 × 10^-3 µm²/s, n = 79 boutons) compared to cMFBs (24.5 ± 3.6 × 10^-3 µm²/s, n = 63; p < 0.001, model F-test), with 2-fold smaller mobile fraction (40 ± 6% vs 76 ± 1%; p < 0.001). Monte Carlo simulations predicted that the higher vesicle density and larger immobile fraction can fully account for the reduced mobility in hMFBs. Simulations of vesicle supply to multiple AZs predicted that the smaller, spatially distributed AZs of cMFBs can support sustained vesicle delivery longer than the larger AZs of hMFBs.

Conclusions. Our results show that cMFBs and hMFBs differ substantially in mitochondrial content, AZ size, vesicle packing and mobility. These ultrastructural differences, and 9-fold difference in vesicle mobility, contribute to their distinct functional properties, supporting higher energy and vesicle supply requirements for sustained rate coding at cerebellar synapses and approximately 4-fold larger pool of docked vesicles required for burst coding at hippocampal synapses.

Ethics. Procedures were carried out in accordance with the UK Animals (Scientific Procedures) Act 1986, approved by relevant institutional ethics committees.

Physiological constraints and ultrasonic hearing in the mammalian cochlea

In young humans, the upper limit of the hearing range is approximately 18 kHz, but in most mammals the range can extend to 100 kHz. The basic physiological tuning mechanism depends on how sound propagates in the fluid of the cochlear duct: it excites a place specific vibration of the basilar membrane (BM) that is enhanced by a population of sensory hair cells, outer hair cells (OHCs). These cells exhibit what is termed ‘electromotility’. Subsequently inner hair cells (IHCs) signal tonotopic information to the brain. Although qualitatively simple, quantitative descriptions are complex and multiscale because 1) the OHC mechano-transduction step is non-linear; 2) there may be intrinsic bandwidth limits to the sensory process either from filtering by the membrane times constant or from inherent limits of the underlying molecular ‘motor (prestin/SLC26A5) and 3) there is limited access to all points along the cochlea and consequent sparse data, although now improving with better imaging technologies.
The approach here is to show that some of these issues can be overcome using a model that incorporates realistic cochlear geometry (Geisler, 1993) and using parameters from a variety of sources. The essential model features include 1) the OHC length which depends, independent of species, on their characteristic frequency; 2) the orientation of the tectorial membrane (TM) which is angled more steeply to the BM as the characteristic frequency increases; 3) a ‘piezo-electric’ property (reverse electromotility) of OHCs, whereby longitudinal force on the cells generates current that compensates for the membrane time constant; 4) an intrinsic time constant (ca 16 us) of relaxation of the prestin/SLC26A5 driving OHC electromotility (Gale & Ashmore, 1997). A Green’s function approach is used to incorporate the effects of fluid coupling between adjacent sections. Reasonable cochlear frequency tuning curves, agreeing with experimental data, can be obtained for both low and high frequencies up to 70 kHz. Age-related human hearing loss may depend on some of these mechanism being compromised.
All computations are performed in a linear approximation appropriate for threshold measurement. A graphic interface written in Matlab will be available on request.

The Rhythm of Drinking: two hierarchically organized signals govern swallow timing in mice

Introduction: Swallowing is an essential step of ingestion that requires the passage of food or drink from the mouth into the gastrointestinal tract. This occurs in the pharynx, a multi-functional space that serves as the entrance to both the digestive and respiratory systems. Given the dual-purpose of the pharynx, swallowing must be correctly timed with concurrent digestive (oral transport) and respiratory (breathing) behaviours to avoid injury, aspiration or choking. Despite this complexity, swallowing occurs seamlessly while eating or drinking in most people. Since it is unknown how these rhythms are organized in drinking mammals and whether sensory input can modulate this organization, we investigated this in mice.

Methods: C57BL6/J mice (n= 8, 5M/3F) were implanted with a stainless-steel head bar to permit head-fixation. Following recovery, mice were restricted to drinking 1 ml of water per day to induce thirst. On test days, this water was delivered on a behavioural apparatus consisting of a lick spout connected to a solenoid-gated fluid delivery system and an external airflow sensor. The experiment consisted of mice licking from the spout, which triggered the solenoid to open and dispense 0.5 µl of water, followed by a short timeout period (200 ms) during which subsequent licks would not open the valve. By measuring solenoid opens and systematically varying the timeout (100-500 ms) we could control the rate of fluid delivery to the mouse and calculate the swallowed volume and the inter-swallow interval.

Results: We identified swallowing as brief (~50 ms) pauses in breathing. These events were nested in the ongoing breathing and licking rhythms, occurring at the phase transition from inhalation to exhalation in breathing and during the tongue retraction phase of licking. This phase-dependency meant that, immediately before a swallow, there was co-incident inhalation and tongue protrusion. We found that when mice were drinking, swallowing occurred at regular intervals. To test whether this was modulated by sensory input, we used a dynamic timeout protocol where the length of time between drops (and therefore the flow rate of the liquid) systematically decreased in 100 ms increments. We found that as the timeout decreased, the inter-swallow interval decreased accordingly. This resulted in a swallow volume ~4 µl across all timeouts.

Conclusion: By monitoring licking, breathing and swallowing during drinking in mice, we discovered two criteria that predict a swallow. First, that the breathing and licking rhythms must be aligned at a specific phase to permit swallowing. Second, swallowing will only occur after a certain volume of fluid has been accumulated and that delaying this rate of accumulation will delay the swallow. Furthermore, these two conditions are organized hierarchically, meaning that aligned breathing and licking only results in a swallow when the volume threshold has been met. This study has unmasked fundamental principles that determine swallow timing in mice and provides an experimental platform for the study of the sensory and circuit mechanisms that generate this behaviour.

Ethics statement: All experiments were performed in accordance with national and Institutional Animal Care and Use Committee guidelines.

The Neonatal Brain at Birth: Region-Specific Neuronal Loss and Parallel Innate Immune Responses Following Intrauterine Escherichia coli K1 Infection

Introduction

Escherichia coli K1 is a leading cause of neonatal bacterial meningitis, carrying 10-15% mortality and leaving 30-50% of survivors with lasting neurological damage. The mechanisms underlying this neuropathology remain poorly understood, particularly the innate immune responses involving resident microglia and peripheral immune infiltration.

Aims

This study aimed to characterise neonatal brains after intrauterine E. coli K1 infection, quantifying neuronal and microglial populations as primary outcomes, with exploratory analysis of mast cell infiltration and cerebellar external granule layer (EGL) thickness.

Methods

Fixed P0 brain tissue was obtained directly from the Boyle et al. (2025) cohort (E. coli K1-infected and PBS control C57BL/6 Tyrc-2J mice; n = 3-4 per group), a timepoint not previously examined in that study. All procedures were conducted under UK Home Office Licence PAD4E6357 in accordance with the Animals (Scientific Procedures) Act 1986. Sections were cut at 70 µm using a Leica vibratome. Immunofluorescence was performed for TUJ1 (neurons), IBA1 (microglia), and tryptase (mast cells), imaged on a Zeiss LSM880 confocal microscope. Cerebellar sections were stained with cresyl violet (Nissl) and imaged on a brightfield microscope. Neuronal and mast cell density were quantified by manual counting in ImageJ; microglial density and morphology were assessed by quantification and Sholl analysis. EGL thickness was measured in Fiji. Group differences were assessed using Welch’s t-tests with the individual brain as the statistical unit.

Results

TUJ1-positive neuronal density was reduced by approximately 60% in infected animals (control: 203 ± 11; infected: 81 ± 6 cells per ROI; n = 3 per group; p = 0.0026). IBA1-positive microglial density was significantly elevated across all three cortical regions examined: lower cortical layer (p = 0.0223), upper cortical layer (p = 0.0402), and cortical white matter (p = 0.0453; n = 3 per group). A trend towards reduced process complexity in infected microglia was observed by Sholl analysis (p = 0.0525; n = 4 per group), consistent with a shift towards an activated morphology. Tryptase-positive mast cell density was approximately 5-fold higher in infected animals (control: 4.67 ± 1.45; infected: 23.67 ± 1.76 cells per section; n = 3 per group; p = 0.0013). Cerebellar EGL thickness was reduced by 34% in infected animals (n = 4 per group; p = 0.0054).

Conclusions

E. coli K1 infection drives significant neuronal loss and concurrent activation of both resident (microglia) and peripheral (mast cell) innate immune populations at birth, alongside disruption of cerebellar development. These findings suggest neuropathology is established at birth and identify mast cell infiltration and cerebellar disruption as novel features of this model. Limitations include small sample sizes (n = 3-4) and a single timepoint. Future work should examine longitudinal trajectories and mast cell-microglia interactions as potential therapeutic targets.

A Perineurial Cell-Mediated Leptin-Sympathetic Axis Protects against Obesity

Introduction:

Obesity is a chronic, multifactorial disease typically associated with hyperleptinemia and leptin resistance, whereby leptin fails to promote its anticipated effects¹. Efforts to better understand and define leptin resistance have largely focused on dissecting the mechanisms behind central leptin resistance. Recent studies show that leptin activates the sympathetic neurons innervating adipose tissue, promoting lipolysis² and thermogenesis³ via neuronally released norepinephrine. Hence, the restoration of leptin sensitivity in adipose tissue could be a therapeutic target for obesity. However, the cellular and molecular players coordinating leptin and sympathetic signalling in adipose tissue remain poorly understood.

Aims/Objectives:

This study aims to identify and characterise cellular mediators coordinating leptin and sympathetic signalling in adipose tissue, and to determine their role in energy homeostasis and obesity.

Methods:

Single-cell RNA sequencing was performed on murine sympathetic ganglia (n = 20 mice) to identify novel cell populations. Conditional knockout mice targeting Adrb2 in Lepr⁺ cells (Adrb2KO) were generated for loss-of-function studies, with littermate controls (Lepr^Cre and Adrb2^fl/fl).

Metabolic phenotyping included body weight and food intake (n = 15-20 per group), energy expenditure (n = 7-10 per group), and thermogenesis (n = 5-7 per group). Histological and apoptosis analyses were conducted in adipose-associated ganglia and sympathetic nerve fibres from high-fat diet-fed obese mice (n = 5 per group). Human genetic association analyses were performed in a European cohort (n = 346,177 individuals) from the UK Biobank.

Data are presented as mean ± SEM. Statistical analyses were performed using unpaired two-tailed Student’s t-tests or one- or two-way ANOVA with appropriate post hoc corrections, as applicable. Statistical significance was defined as p < 0.05.

All animal procedures were conducted in accordance with the UK Animals (Scientific Procedures) Act 1986 and approved by the institutional Animal Welfare and Ethical Review Body. Human genetic analyses were performed on de-identified data from approved cohorts with relevant ethics committee approval.

Results:

Using single-cell RNA sequencing on murine sympathetic ganglia, we identified a unique population of perineurial cells expressing both the leptin receptor (Lepr) and the β2 adrenergic receptor (Adrb2)⁴. Sympathetic Perineurial Cells (SPCs) form a barrier surrounding sympathetic ganglia and nerve bundles in adipose tissue and display molecular features resembling endothelial cells. Conditional knockout of Adrb2 in Lepr⁺ SPCs predisposes mice to obesity by lowering energy expenditure and thermogenic activity without affecting food intake. Notably, we found that obesity-driven hyperleptinemia causes apoptosis in SPCs, leading to a significant erosion of the perineurial barrier and concomitant sympathetic neuropathy. We further show that this deleterious effect can be reversed by partial reduction of leptin or by β2 adrenergic receptor agonism. Supporting translational relevance, we confirmed the presence of LEPR⁺ ADRB2⁺ SPCs in human sympathetic ganglia. We also observed a synergistic effect of highly common polymorphisms in LEPR and ADRB2 on the risk of increased BMI in a large European population.

Conclusion:

These findings identify SPCs as a critical neuroendocrine interface integrating leptin and sympathetic signalling in adipose tissue and support a revised model of the leptin set point beyond central appetite regulation.

Betaine ameliorates doxorubicin-induced cardiorenal toxicity in rats.

Introduction: Doxorubicin (DOX) is a potent chemotherapeutic agent whose clinical utility is severely limited by dose-dependent cardio- and nephrotoxicity. Betaine, a methyl donor and major renal osmolyte, has been suggested to maintain cardiovascular homeostasis and improve renal function through antioxidant and potential diuretic mechanisms[1, 2].

Aims: This study evaluated the protective effects of betaine against DOX-induced injury in heart and kidney tissues by assessing hemodynamic, biochemical, and molecular parameters.

Methods: Male Sprague-Dawley rats (n=36) were randomized into four groups: Control (tap water; n= 8); Betaine (0.5% solution in water, n= 8); DOX (i.p. injections, cumulative dose 15 mg/kg bw, n=10); and DOX+Betaine (n=10). After eight weeks, 24-hour water and food balance were evaluated in metabolic cages. Subsequently, echocardiography and hemodynamic recordings were performed under urethane anaesthesia (1.5 g/kg bw i.p.). Plasma NT-proBNP and urinary KIM-1 were measured via ELISA. Biochemical parameters including proteinuria were determined using a Cobas 6000 analyzer. Antioxidant enzymes (catalase, SOD1) were quantified by Western blot in the heart, renal cortex, and medulla. Data were analyzed via ANOVA with Tukey’s or Kruskal-Wallis with Dunn’s post-hoc tests (p < 0.05). All procedures were approved by the Local Ethics Committee and accorded with international guidelines and legislation.

Results: DOX administration significantly increased mean arterial blood pressure (MABP) (DOX: 134.6±2.6 vs Control: 115.3±2.3 mmHg; p < 0.001) and plasma NT-proBNP levels (51.8±5.1 vs 22.8±3.7 pg/ml; p = 0.009). Renal damage was evidenced by elevated urinary KIM-1 (6352±279 vs 2781±597 pg/ml; p < 0.001) and marked proteinuria (2018.9±1320 vs 144.9±41.3 mg/dl, p < 0.001). Histopathological analysis confirmed morphological damage in both cardiac and renal tissues. Betaine supplementation significantly attenuated proteinuria (639.7±439.6 mg/dl, p < 0.05 vs DOX) and urinary KIM-1 levels (2376±342 pg/ml, p < 0.05 vs DOX). It also partially mitigated the rise in MABP (125.9±3.5 mmHg) and NT-proBNP (38.3±7.7 pg/ml), while improving tissue morphology. Notably, betaine did not significantly alter urine excretion rates or the expression of antioxidant enzymes (SOD1, catalase) in the heart or kidney. Data are expressed in means±SE.

Conclusions: Dietary betaine provides significant protection against DOX-induced cardiorenal injury. These protective effects appear to be independent of antioxidant enzyme modulation or diuretic actions, suggesting alternative mechanisms of action. These findings support the investigation of betaine as a non-pharmacological dietary strategy to mitigate chemotherapy-induced toxicity.

Figure 1. Box plots showing biochemical markers of kidney damage in experimental groups. * p < 0.05 by ANOVA with Tukey’s post-hoc test or by Kruskal-Wallis with Dunn’s post-hoc test.

Figure 2. Box plots showing NT pro-BNP and hemodynamic parameters in experimental groups. * p < 0.05 by ANOVA with Tukey’s post-hoc test or by Kruskal-Wallis with Dunn’s post-hoc test.

Investigating the effect of oxytocin on the inner and outer layers of the pregnant and non-pregnant human myometrium

Introduction:

Contractions of the myometrium, the muscle layer of the uterus, serve several physiological functions including menstruation and labour, with aberrant contractions associated with benign gynaecological disorders and obstetric complications such as adenomyosis and dystocia. The myometrium consists of three layers: the sub-endometrial inner (IM), sub-serosal outer (OM), and middle myometrium. Despite animal studies suggesting distinct contractile properties and physiological functions of the IM and OM, equivalent functional characterisation in humans is lacking.

Aim:

To characterise regional differences in the effect of oxytocin on human myometrium.

Methods:

Myometrial biopsies were collected from term-pregnant women undergoing elective caesarean section (n=17) and nonpregnant women (n=4) undergoing hysterectomy for benign gynaecological conditions at Liverpool Women’s Hospital with informed, written consent and REC approval (REC 10/H1002/49).

Paired strips (5x2x1mm) from the IM and OM were mounted in organ baths to record isometric tension. The effect of oxytocin (10^-10-10^-6M) on contraction amplitude (mN), mean integral of force (MIF, a.u), frequency (contractions/hour), and duration (min) were assessed relative to spontaneous contractions (taken as 100%). Concentration-response curves determined maximum effect (Emax). OM and IM responses were compared via paired Student’s t-test or Wilcoxon signed rank test, P<0.05 was significant.

Results:

Mean amplitude of pregnant IM spontaneous contraction was greater (9.27mN, SE 1.61) than the OM (6.24mN, SE 0.91) but not significant (P=.06, n=17). Similarly, nonpregnant IM mean contraction amplitude was greater (6.12mN, SE 2.18) than the OM (3.94mN, SE 0.807) (P=.31, n=4). No significant regional differences in duration, frequency, or MIF of spontaneous contractions were observed in the pregnant or nonpregnant myometrium.

Oxytocin increased mean contraction amplitude and MIF in both regions of the pregnant myometrium in a concentration-dependent manner (n=10). Amplitude Emax in the OM was 256% of control (SE 39.6) compared to 163% (SE 15.4) in the IM, but not significantly greater (P=.06). Overall MIF Emax in the OM and IM was equal; OM, 322% of control (SE 51.0) and IM, 328% of control (SE 45.2) (P=.1). A dose-dependent reduction in contraction frequency and prolongation of duration was observed in both layers, with no regional difference noted.

Similarly, a dose-dependent stimulatory effect of oxytocin on contraction amplitude and MIF was demonstrated in both regions of the nonpregnant myometrium (n=4). Contrasting with the pregnant myometrium, a trend toward increased response in the IM compared to the OM was observed. Dose-response curves were not fit due to sample size.

Comparing oxytocin’s effect in the pregnant and nonpregnant myometrium, oxytocin induced a significantly smaller uterotonic effect in the nonpregnant OM compared to the pregnant OM; 114% of control (SE 7.20) vs. 233% (SE 40.1) (P=.04). The same trend was observed in the IM, although not significant.

Conclusions:

Regional specific differences in spontaneous myometrial contractile activity highlight potential functional differences between the IM and OM, possibly supporting distinct physiological roles. An increased response to oxytocin in the pregnant myometrium and specifically in the OM, supports the proposed role of the OM in facilitating the powerful contractions in labour. The opposite layer-specific sensitivity to oxytocin in the nonpregnant myometrium may indicate processes relevant to nonpregnant uterine function, which warrant further investigation.

The Prognostic Value of Skin Temperature Variability Analysis in Humans: A Systematic Review

Introduction:
Skin temperature fluctuates dynamically and reflects complex thermoregulatory mechanisms, including the balance between heat loss and heat gain mechanisms through autonomic control of peripheral blood flow and metabolic factors. While analytical methods have been established to assess skin temperature variability (STV), the potential applications of STV analysis remain an emerging and primarily exploratory field. This systematic review aims to synthesize current evidence on the prognostic role of STV metrics, including short-term fluctuations, circadian patterns, and entropy in predicting clinical outcomes such as mortality. It also seeks to characterise the technical heterogeneity in measurement sites and analytical approaches, and to identify future research directions.

Methods:
Following PRISMA guidelines, a systematic search was conducted across Ovid MEDLINE, EMBASE, and AMED from inception to July 2025. Studies were eligible if they included human participants in any clinical setting and linked dynamic STV measurements to prognostic outcomes. The quality of the included studies was assessed using the QualSyst tool. As this study is a systematic review of previously published data and did not involve new data collection from human participants or animals, no ethical approval was required.

Results:
Of 123 papers screened, a total of 8 studies met the inclusion criteria. Preliminary evidence suggests an association between altered STV and patient prognosis, although the findings are limited by methodological heterogeneity:

1. Population-Level Findings: Large-scale data from the UK Biobank (n=91,462) identified that blunted circadian temperature amplitudes are independent predictors of long-term incident diseases, including Non-alcoholic Fatty Liver Disease (HR: 1.91) and Type 2 Diabetes (HR: 1.69).

2. Clinical Cohort Findings: Seven smaller observational cohorts (n=21 to 66) demonstrated that reduced signal complexity (entropy), loss of short-term variability, and increased thermal instability were associated with higher mortality risks (OR: 1.41) and lower event-free survival across acute and chronic conditions, including sepsis, cirrhosis, and ischaemic heart disease.

3. Methodological Heterogeneity: Significant variability was observed across studies regarding measurement sites (e.g., axilla, wrist, hypochondrium), sampling frequencies (ranging from every 10 seconds to three times daily), and analytical approaches, including amplitude, entropy, and short- and long-term variability.

A process-based logic model was developed to map the conceptual relationships between patient populations, measurement sites, STV metrics, and clinical outcomes (Figure 1).

Conclusion:
STV analysis shows promise as a non-invasive tool for identifying physiological vulnerability across a wide spectrum of clinical conditions. However, the current evidence is predominantly exploratory and constrained by small sample sizes and high methodological heterogeneity. Future research should focus on large-scale validation studies and standardizing STV metrics to facilitate their integration into wearable technology and real-time clinical monitoring systems.

Membership category	Early registration rate until 16 May 2026	Standard registration rate until 16 June 2026
Member	£0	£0
Non-member	£0	£0

Registration opens	24 March 2026
Abstract submission opens	24 March 2026
Abstract submission closes	26 May 2026
Early bird registration deadline	16 May 2026
Conference Attendance Award deadline	30 April 2026
Registration deadline	16 June 2026
Meeting dates	30 June – 1 July 2026

Become a member

Check out our Training Hub

What is physiology?

Meet our members

Advancing Physiology Together: Showcasing Research, Enhancing Careers, and Building Communities

Celebrating Physiology in London

Date

Location

Member fee

Non-member fee

09:30 SA01 Synaptic signaling in the human hippocampal CA3 network

10:00 C01 Presynaptic ultrastructure and vesicle mobility at cerebellar and hippocampal mossy fibre boutons support their functional divergence

10:15 C02 Physiological constraints and ultrasonic hearing in the mammalian cochlea

10:30 C03 Four phases and a temporal threshold of population calcium response in cortical astrocytes during locomotion

10:45 C04 The Rhythm of drinking: Two hierarchically organized signals govern swallow timing in mice

11:30 PL04 Structural synaptic plasticity during long-term potentiation (LTP)

13:30 SA02 Nanostructural regulation of synaptic transmission

14:00 C05 The neonatal brain at birth: Region-specific neuronal loss and parallel innate immune responses following intrauterine escherichia coli K1 infection

14:15 C06 A perineurial cell-mediated leptin-sympathetic axis protects against Obesity

14:30 C07 Betaine ameliorates doxorubicin-induced cardiorenal toxicity in rats

14:45 C08 Investigating the effect of oxytocin on the inner and outer layers of the pregnant and non-pregnant human myometrium

15:30 SA03 Location-dependent cholinergic biased signalling regulates axonal intrinsic plasticity in hippocampal neurons

16:00 C10 The prognostic value of skin temperature variability analysis in humans: A systematic review

Registration

Member registration

Non-member registration

Applying for a visa

Abstracts

Key Information

Key dates

Venue

Support to Attend

Grants for Carers

Conference Attendance Award

Site search

Filter

Content Type