bioRxiv Subject Collection: Neuroscience's Journal
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Wednesday, September 24th, 2025
| Time |
Event |
| 9:17a |
Emergence of Functional Heart-Brain Circuits in a Vertebrate
The early formation of sensorimotor circuits is essential for survival. While the development and function of exteroceptive circuits and their associated motor pathways are well characterized, far less is known about the circuits that convey viscerosensory inputs to the brain and transmit visceromotor commands from the central nervous system to internal organs. Technical limitations, such as the in utero development of viscerosensory and visceromotor circuits and the invasiveness of procedures required to access them, have hindered studies of their functional development in mammals. Using larval zebrafish, which are genetically accessible and optically transparent, we tracked, in vivo, how cardiosensory and cardiomotor neural circuits assemble and begin to function. We uncovered a staged program. First, a minimal efferent circuit suffices for heart-rate control: direct brain-to-heart vagal motor innervation is required, intracardiac neurons are not, and heart rate is governed exclusively by the motor vagus nerve. Within the hindbrain, we functionally localize a vagal premotor population that drives this early efferent control. Second, sympathetic innervation arrives and enhances the dynamics and amplitude of cardiac responses, as neurons in the most anterior sympathetic ganglia acquire the ability to drive cardiac acceleration. These neurons exhibit proportional, integral, and derivative-like relationships to heart rate, consistent with controller motifs that shape gain and dynamics. Third, vagal sensory neurons innervate the heart. Distinct subsets increase activity when heart rate falls or rises, and across spontaneous fluctuations, responses to aversive stimuli, and optogenetically evoked cardiac perturbations, their dynamics are captured by a single canonical temporal kernel with neuron-specific phase offsets, supporting a population code for heart rate. This temporally segregated maturation isolates three experimentally tractable regimes, unidirectional brain-to-heart communication, dual efferent control, and closed-loop control after sensory feedback engages, providing a framework for mechanistic dissection of organism-wide heart-brain circuits. | | 10:31a |
A mechanistic theory of planning in prefrontal cortex
Planning is critical for adaptive behaviour in a changing world, because it lets us anticipate the future and adjust our actions accordingly. While prefrontal cortex is crucial for this process, it remains unknown how planning is implemented in neural circuits. Prefrontal representations were recently discovered in simpler sequence memory tasks, where different populations of neurons represent different future time points. We demonstrate that combining such representations with the ubiquitous principle of neural attractor dynamics allows circuits to solve much richer problems including planning. This is achieved by embedding the environment structure directly in synaptic connections to implement an attractor network that infers desirable futures. The resulting 'spacetime attractor' excels at planning in challenging tasks known to depend on prefrontal cortex. Recurrent neural networks trained by gradient descent on such tasks learn a solution that precisely recapitulates the spacetime attractor - in representation, in dynamics, and in connectivity. Analyses of networks trained across different environment structures reveal a generalisation mechanism that rapidly reconfigures the world model used for planning, without the need for synaptic plasticity. The spacetime attractor is a testable mechanistic theory of planning. If true, it would provide a path towards detailed mechanistic understanding of how prefrontal cortex structures adaptive behaviour. | | 10:31a |
Exploring the impact of social relevance on the cortical tracking of speech: viability and temporal response characterisation
Human speech is inherently social. Yet our understanding of the neural substrates underlying continuous speech perception relies largely on neural responses to monologues, leaving substantial uncertainty about how social interactions shape the neural encoding of speech. Here, we bridge this gap by studying how EEG responses to speech change when the input includes a social element. Specifically, we compared the neural encoding of synthesised undirected monologues, directed monologues, and dialogues in Experiment 1. In Experiment 2, we extended this by using podcasts, addressing the additional challenges of real speech dialogue, such as dysfluencies. Using temporal response function analyses, we show that the presence of a social component strengthens envelope tracking - despite identical acoustic properties - indicating heightened listener engagement. Neural responses to synthesised speech showed a strong correlation with those for real speech podcasts, with a stronger alignment emerging for more socially-relevant speech material. In addition, we demonstrate that robust neural indices of sound and lexical-level processing can be derived using real podcast recordings despite the presence of dysfluencies. Finally, we discuss the importance of dysfluency in social speech experiments, presenting a simulation quantifying the potential impact of dysfluency on lexical level analyses. Together, these findings advance our understanding of continuous speech neurophysiology by highlighting the impact of social elements in shaping auditory neural processing in a controlled manner and providing a framework for future investigation and analysis of social speech listening and speech interaction. | | 12:32p |
Inferring systemic metabolic and oxidative stress susceptibility in normal-tension glaucoma through targeted skin fibroblast analysis
Aim: Enhance the understanding of intrinsic metabolic and oxidative stress vulnerability in normal-tension glaucoma (NTG) pathophysiology by targeted profiling of skin fibroblasts from NTG and control donors. Background: NTG is a primary open-angle glaucoma subtype characterised by glaucomatous neurodegeneration without elevated intraocular pressure. Increasing evidence links systemic metabolic and oxidative stress vulnerability to NTG pathophysiology, making non-ocular, somatic cells promising surrogate systems for assessing neurodegenerative predisposing mechanisms. Methods: Skin fibroblast cultures were obtained from four female NTG and four age- and gender-matched control donors. Targeted metabolic profiling of mitochondrial function, glycolytic capacity, and glucose and amino acid metabolism was performed using the seahorse assay, gas chromatography-mass spectrometry, and high-performance liquid chromatography. Oxidative stress resilience to hydrogen peroxide was assessed employing the lactate dehydrogenase release assay. Results: Pure skin fibroblast cultures were obtained for all included donors. NTG and control fibroblast exhibited similar mitochondrial and glycolytic function. No group difference was demonstrated in relative glucose metabolism and absolute amino acid profile. Control and NTG fibroblasts exhibited similar susceptibility to oxidative stress. Conclusion: NTG skin fibroblasts exhibit similar mitochondrial and glycolytic function, glucose metabolisation, amino acid profile, and oxidative stress resiliency compared to controls. Future studies should focus on mapping cell- and tissue-specific differences through combined genetic and transcriptomic profiling to guide and stratify the functional assessment of different endotypes within the NTG disease spectrum. Cell-specific dysregulation and the need for individual mechanistic grouping diminish the applicability of skin fibroblasts as a model system for exploiting NTG pathophysiology. | | 5:35p |
Improving the learning curve in monoportal endoscopic lumbar surgery: development and validation of a porcine training model.
Study design Experimental animal study. Purpose Endoscopic spine surgery (ESS) has gained substantial traction globally. Proficiency in ESS demands a steep learning curve and rigorous technical training. This study aims to develop and validate a porcine model as a high-fidelity, reproducible platform for hands-on training in lumbar endoscopic procedures. Methods Thirteen skeletally mature Landrace x Large white pigs underwent lumbar endoscopic decompression via a transforaminal approach at L4-L5 and an interlaminar approach at L5-L6. Specific procedural modifications were introduced to optimize anatomical correlation and surgical ergonomics. Following a seven-day postoperative period, necropsies were performed to evaluate procedural outcomes and adverse events. Operative times, intraoperative events, and postoperative outcomes were systematically recorded. Results Endoscopic decompression was successfully completed in all specimens. Mean operative time was 134.7 {+/-} 32.3 minutes. Intraoperative complications occurred in 4 animals (30.8%): uncontrollable epidural bleeding (case 1), dural tear (case 7), technically difficult transforaminal access in a low-weight pig (33.8 kg, case 8), and a complex interlaminar approach leading to spinal cord injury (case 13). One additional animal (case 4) developed paraplegia without structural findings at necropsy, attributed to intraoperative positioning. Necropsy revealed asymptomatic epidural hematomas in three cases (9, 11, 12). Three animals (23.1%) required early euthanasia based on humane criteria. A significant learning curve effect was demonstrated, with operative time decreasing over the series ({rho} = -0.73, p = 0.004). Conclusions The porcine lumbar spine provides a reliable and anatomically valid model for ESS training. Awareness of species-specific anatomy, specimen size, and positioning is essential to maximize reproducibility and safety. | | 6:47p |
Neuronal detection of social actions directs collective escape behavior
Animals in groups obtain information from their social partners to engage in collective behavior. Social information transmission has been observed amongst individuals in fish schools, bird flocks, and human groups, but the neural mechanisms for detecting socially transmitted information are poorly understood. By studying the schooling glassfish Danionella cerebrum, here we demonstrate that escape from danger is enhanced by visual perception of other escaping fish. We found that neural populations in the midbrain optic tectum and dorsal thalamus are activated by the rapid escape of social partners. These neurons are also driven by the sudden disappearance of virtual social partners, yet unaffected by disappearing stimuli without social relevance. Virtual fish schools that escape or disappear were sufficient to cause observers to escape, even in the absence of direct threats. These results demonstrate that rapid social-off detection in visual circuits enables the detection of socially transmitted threat information, which may be a particularly effective strategy for animals capable of rapid movement but limited visual range. These results show how neural computations in individuals enables rapid information sharing in animal collectives. | | 6:47p |
Perceiving less or perceiving unreliably? Disentangling thermosensory sensitivity and precision in the contexts of ageing and neuropathy
Thermal perception is determined not only by sensitivity but also by precision, yet the latter is often overlooked in thermosensation and pain research. This study examined how ageing and diabetic polyneuropathy (DPN) affect the sensitivity and precision of thermal perception and whether combining these parameters can aid in distinguishing patients from healthy controls. Using a Bayesian hierarchical modelling approach, we estimated psychometric function thresholds (sensitivity) and slopes (precision) for cold detection, warm detection, cold pain, and heat pain in 86 healthy adults (aged 21-80) and 34 patients with DPN. We assessed age- and neuropathy-related effects on these parameters. Using simulated classification analyses, we also tested their utility in discriminating patients from controls. Ageing was associated with elevated detection and cold pain thresholds and reduced precision of cold detection. Patients with DPN showed similar patterns: higher detection thresholds and lower cold detection slopes while pain-related parameters were largely unaffected. These findings indicate that ageing and neuropathy produce qualitatively similar changes in thermosensory function, particularly affecting cold detection sensitivity and precision. Classification based on detection thresholds and cold detection slope successfully discriminated patients from controls, with cold detection slope offering the best performance. Combining threshold and slope parameters did not significantly improve classification accuracy. Accurate classification was not possible based on pain thresholds and slopes. Modelling both thresholds and slopes provides a more comprehensive view of sensory decline and may enhance the detection of early or subtle sensory dysfunction. | | 6:47p |
Cortex-Wide Substrates for Body Schema and Action Awareness
The body schema, an internal model of the body's configuration in space, is essential for embodied perception and voluntary action. Cortical lesions can disrupt the body schema; however, it remains unclear how the cortex efficiently represents the vast repertoire of body postures during natural behavior. Here, we unveil the representational format underlying the body schema by combining large-scale electrophysiology with 3D full-body motion capture in freely moving mice. Across posterior parietal (PPC) and sensorimotor cortices (SMC), neurons encoded diverse postural features in distinct reference frames: PPC neurons emphasize midline-referenced features related to left-right turning, whereas SMC neurons encode body elevation and pitch relative to the ground, revealing a gravicentric reference frame. Strikingly, beyond static posture encoding, we identified neural ensembles selectively activated during stereotyped actions such as walking, rearing, and grooming. These action ensembles fire in phase-locked sequences that tile the entire action cycle, providing a substrate for action awareness. A network model recapitulated these dynamics, showing that population activity clustered into action-specific subspaces. Together, these findings demonstrate that the cortex organizes the body schema around actions, compressing high-dimensional kinematics into an efficient, gravity-anchored, and action-aware neural code. | | 8:47p |
A neural circuit for female-specific defensive homeostasis in risk assessment
Risk assessment in defensive behavior is an adaptive mechanism shaped by natural selection, enabling individuals to evaluate potential threats and thereby maintain defensive homeostasis. Although risk assessment is essential for survival, it remains unknown whether specific neural circuits maintain their behavioral homeostasis in a sex-specific manner. Here, we show that visual survival threats activated cannabinoid 1 receptor (CB1R)-expressing neurons in the superior colliculus (SC), initiating consistent risk assessment in both sexes. Deletion of CB1R in SC GABAergic neurons female-specifically impairs risk assessment by disinhibiting GABA release in SC-lateral habenula (LHb) projections, resulting in abnormally shortened risk assessment. Furthermore, loss of CB1R in SC GABAergic neurons increases the occurrence of abnormal spontaneous behavior following chronic stress exclusively in females. Our findings revealed a female-specific CB1R-modulated SC-LHb GABAergic circuit crucial for maintaining defensive homeostasis in risk assessment, highlighting how disruptions in this circuit underlie deficits in risk assessment and adaptive stress coping. | | 8:47p |
Prolonged oscillating kisspeptin neuron activity underlies the preovulatory luteinizing hormone surge in mice
The population of kisspeptin neurons located in the rostral periventricular area of the third ventricle (RP3V) is thought to have a key role in generating the GnRH surge that triggers ovulation. Using a modified GCaMP fibre photometry procedure, we have been able to record the in vivo population activity of RP3VKISS neurons across the estrous cycle of female mice. A marked increase in GCaMP activity was detected beginning on the afternoon of proestrus that lasted in total for 13{+/-}1 hours. This was comprised of slow baseline oscillations with a period of 91{+/-}4 min and associated with high frequency rapid transients. Very little oscillating baseline or transient activity was detected at other stages of the estrous cycle. Concurrent blood sampling showed that the peak of the LH surge occurred 3.5{+/-}1.1 h after the first baseline RP3VKISS neuron baseline oscillation on the afternoon of proestrus. The time of onset of RP3VKISS neuron oscillations varied between mice and across subsequent proestrous stages in the same mice. To assess the impact of estradiol on RP3VKISS neuron activity, mice were ovariectomized and given an incremental estradiol replacement regimen. Minimal patterned GCaMP activity was found in OVX mice, and this was not changed acutely by any of the estradiol treatments. However, on the afternoon of the expected LH surge, the same oscillating baseline activity with associated transients occurred for 7.1{+/-}0.5 h. These observations reveal an unexpected prolonged oscillatory pattern of RP3VKISS neuron activity that is dependent on estrogen and underlies the preovulatory LH surge as well as potentially other facets of reproductive behavior. | | 9:20p |
Blood-derived dietary protein promotes sleep in the mosquito Aedes aegypti
Sleep is a ubiquitous, yet highly variable, behavior across species. The duration and timing of sleep are influenced by ecological demands and dietary context. In the mosquito Aedes aegypti, a blood feeding insect with specialized nutritional requirements, the relationship between feeding and sleep remains poorly understood. Here, we investigate how blood derived dietary protein influences sleep regulation. Using postural analysis, videography, and arousal threshold assays, we establish that immobility bouts of greater than 10 minutes reliably define sleep in Ae. aegypti. Infrared activity monitoring revealed that blood-fed females exhibit a marked increase in sleep beginning immediately after feeding and persisting for several days, accompanied by reduced locomotor activity. Notably, this sleep elevation lasts well beyond the cessation of host-seeking behavior, suggesting distinct phases of opportunistic versus determined host pursuit. To determine the dietary basis of this effect, we tested mosquitoes fed a bovine serum albumin (BSA) based diet. BSA feeding alone was sufficient to mimic the sleep-promoting and hypoactive effects of blood, identifying dietary protein as the key nutritional regulator. Moreover, RNAi mediated knockdown of the leucokinin receptor (lkr), previously implicated in fluid regulation and feeding, enhanced sleep and reduced activity, implicating LK signaling in postprandial sleep modulation. Together, these findings demonstrate that blood-derived proteins drive sustained increases in sleep and reduced locomotion in Ae. aegypti. This work positions Ae. aegypti as a model for dissecting nutrient-specific regulation of sleep and highlights potential adaptive functions of protein-induced quiescence, such as energy conservation and predator avoidance. More broadly, it provides insight into how specialized diets shape the neural and behavioral architecture of sleep. | | 10:32p |
Context rescales a social action code in a hormone-sensitive network
Deciding whether and when to engage in social interaction depends on external factors including the location of the interaction and the identity of the social partner (the social context) as well as internal factors such as an individual's hormonal state. However, we lack a mechanistic understanding of how external and internal variables coordinate social action through networks of hormone-sensitive neurons. In particular, while gonadal hormones have long been suggested to coordinate territorial behaviors, direct evidence of how this coordination occurs has been lacking. To answer this, we combined large-scale neural recordings with large-scale unsupervised behavioral quantification to track neural activity longitudinally across a hormonal perturbation. We recorded neural population activity from neurons expressing the hormone receptor estrogen receptor alpha (esr1+) as well as from local esr1- neurons across the subcortical Social Behavior Network (SBN) and compared neural responses and behavior across social contexts with varied partners and territories. Using a comprehensive behavioral quantification strategy, we observe that patterns of social action and their underlying neural dynamics differentiate social partner and territory in both sexes. We find that each context has a unique behavioral action code, and that territory naturally rescales the partner-specific social action code in the hormonally intact state. However, when levels of circulating gonadal hormones are reduced, we observe that patterns of behavior during interactions in the home territory in males are disrupted, and that these changes can be rescued by testosterone replacement. Critically, hormonal perturbation disrupts territorial rescaling in a population-specific manner. Together, these data demonstrate how a loss of circulating hormones alters the relationship between social context and social action to disrupt context-specific social decision making. |
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