The neural circuits processing thermal information play a key role in shaping somatosensory perception, regulating core body temperature and avoiding harm. The circuits underlying thermal perception are less understood than for other sensory systems, but recent research has shed light on the wiring, cellular encoding principles and their link to perception. While thermosensation was traditionally viewed as a slower, modulatory sense, it is now recognized as a fast and sensitive sensory system that exhibits complex features such as multisensory integration and sensory illusions. Here, we highlight recent progress in the understanding of innocuous thermal processing and perception and attempt to identify the principles of wiring of the thermal system and cellular encoding of temperature across mammals and insects. Intriguingly, while warm and cool reflect the same physical property, there are notable differences in their perception and encoding in the nervous system. We argue that the thermal system is an ideal model to advance our understanding of the neural mechanisms of sensory perception and sensory-guided behaviours.

Artificial intelligence has created tremendous advances for many scientific and engineering applications. In this Review, we synthesize recent advances in joint brain-behaviour modelling of neural and behavioural data, with a focus on methodological innovations, scientific and technical motivations, and key areas for future innovation. We discuss how these tools reveal the shared structure between the brain and behaviour and how they can be used for both science and engineering aims. We highlight how three broad classes with differing aims - discriminative, generative and contrastive - are shaping joint modelling approaches. We also discuss recent advances in behavioural analysis approaches, including pose estimation, hierarchical behaviour analysis and multimodal-language models, which could influence the next generation of joint models. Finally, we argue that considering not only the performance of models but also their trustworthiness and interpretability metrics can help to advance the development of joint modelling approaches.

Half a century of neurophysiological recordings from single electrodes established a 'localized' viewpoint on function in the brain - that complex behaviour results from computations that are carried out and representations that occur across distinct brain areas, each of which has a specialized role. Data generated from new techniques for specific, high-throughput measurement of neuronal activity and behaviour in rodents have prompted an alternative viewpoint, which posits that neural encoding of behavioural variables is distributed across a wide range of areas: 'everything, everywhere, all at once'. After briefly introducing these paradigms, we evaluate which of them better describes cognition - the manipulation of internal variables that enables flexible behaviour. Measurements of neuronal activity in both rodents and primates suggest that cognitive variables are reflected broadly but not ubiquitously across the brain, including, to a surprising degree, in regions engaged in controlling movement. We close by discussing why cognitive signals may appear in such areas, as well as the factors that affect the breadth of the brain-wide network that is recruited for cognition.

Programmed axon degeneration (PAxD) is an evolutionarily conserved mechanism in the nervous system that is activated by axonal injury (axotomy) to execute the self-destruction of a severed distal axon. It can also be triggered by non-axotomy insults, resulting in the loss of axons connected to their cell bodies. PAxD is therefore a promising target for therapeutic intervention and drugs that inhibit it are currently being tested in clinical trials. In this Review, we summarize the molecular mechanism of PAxD, focusing on its regulation by nicotinamide adenine dinucleotide (NAD) metabolism and how it dictates Ca-mediated axonal demise. We examine its involvement in human disease and its potential as a therapeutic target by dissecting its role in various non-axotomy disease models. Finally, we address key challenges for its clinical translation, including the need for relevant biomarkers and safety considerations. Further advancements in understanding PAxD will pave the way for new therapeutic strategies targeting human axonopathies.

Time and space are crucial concepts in neuroscience, because our personal memories are tied to specific events that occur 'in' a particular space and on a 'timeline'. Thus, we seek to understand how the brain constructs time and space and how these are related to episodic memory. Place cells and time cells have been identified in the brain and have been proposed to 'represent' space and time via single-neuron or population coding, thus acting as hypothetical coordinates within a Newtonian framework of space and time. However, there is a fundamental tension between the linear and unidirectional flow of physical time and the variable nature of experienced time. Moreover, modern physics no longer views space as a fixed container and time as something in which events occur. Here, I articulate an alternative view: that time (physical and experienced) is an abstracted relational measure of change. Physical time is measured using arbitrary units and artificial clocks, whereas experienced time is linked to a hierarchy of brain-body rhythms that provide a range of reference scales that reflect the full span of experienced time. Changes in body and brain circuits, tied to these rhythms, may be the source of our subjective feeling of time.

Stroke remains a leading cause of disability owing to the irreversible neuronal loss that it causes and the limited regenerative capacity of the CNS. Although reperfusion therapies such as thrombolysis and mechanical thrombectomy can restore blood flow after stroke, their stringent eligibility criteria leave many patients without treatment options. The immune response, involving complex interactions between brain-resident and peripheral immune cells, has a critical role in stroke recovery. Stem cell-based therapies, particularly those involving neural stem cells and mesenchymal stem cells, may be able to reshape the inflammatory microenvironment after stroke, mitigating secondary injury and promoting tissue repair. However, the precise mechanisms driving their effects remain incompletely understood, hindering clinical translation. In this Review, we highlight the bidirectional crosstalk between stem cells and immune cells (including microglia, T cells and peripheral immune cells) and discuss how these interactions influence neuroinflammation, neural plasticity and circuit remodelling in stroke recovery. We examine key determinants of stem cell therapy efficacy, emphasizing the role of stem cell-immune cell interactions, and discuss targeted strategies to enhance immune modulation and neuroprotection.

Emerging evidence highlights the crucial role of peripheral immune cells in maintaining brain homeostasis and their influence on the pathology of Alzheimer disease (AD). Genome-wide association studies have identified numerous AD risk variants in genes expressed by immune cells, implicating innate and adaptive immune pathways in disease progression. Advances in neuroimmunology have revealed that immune cell crosstalk involving T cells, B cells, monocytes and/or macrophages and neutrophils can modulate the hallmark features of AD, including amyloid plaque accumulation, tau pathology and chronic neuroinflammation. Mechanistic insights suggest that chronic peripheral inflammation, immune exhaustion, metabolic dysfunction and epigenetic reprogramming exacerbate neurodegeneration in AD by promoting toxic inflammation and impairing protein clearance in the brain. These findings may catalyse the development of novel immunomodulatory strategies, such as immune checkpoint inhibition and cytokine targeting, among others, for AD. This Review examines peripheral immune alterations in AD, evaluates related therapeutic opportunities and highlights key knowledge gaps, particularly the need for human-derived data to advance translational progress. Future research should prioritize personalized approaches that integrate genetic risk, immune profiling and ageing to inform next-generation therapies for AD.

Human sociality is grounded in the dynamic coordination of individuals as they interact with one another. Indeed, various levels of interpersonal coordination - neural, behavioural, physiological, affective, linguistic - are hallmarks of successful social communication and cooperation. However, describing these complex, interdependent dynamics has been limited by current methodological approaches, owing to a restrictive repertoire of tools and the absence of a unified, standardized methodological framework. Here, we identify information theory - the mathematical theory of communication - as a particularly well-suited conceptual framework to address this shortfall, given its appropriate sensitivity to complex dynamics, including potential nonlinearity and higher-order interactions, and its data-driven, model-agnostic foundations. With deep roots in computational, cognitive and systems neuroscience, the formal introduction of information-theoretic quantities and methods into the study of interpersonal coordination is perhaps overdue. In this Perspective, we advance the case for a unified information-theoretic framework for the field while paving the way for a new generation of empirically testable, theoretically grounded research questions.