Reviews & Analysis

Despite rapid exploitation of the opportunities that contextualization of brain maps affords, potential limitations have received little attention. In this Roadmap, Royer et al. provide practical guidelines operating at the level of study design, analysis pipelines and interpretation of findings to encourage the development of best practices in data contextualization in neuroscience.

Astrocytic Ca²⁺ signalling is a fundamental and highly spatiotemporally nuanced mechanism for maintaining brain homeostasis. In this Review, Bacskai and colleagues discuss how astrocytic Ca²⁺ homeostasis is altered in ageing and neurodegenerative diseases and plays a central role in neurodegenerative pathophysiology.

Appeals to representation are widespread, despite neuroscientists’ uncertainty about what kind of findings count as evidence for such claims. In this Perspective, Pohl and colleagues develop a unified framework that distinguishes four conceptual dimensions relevant to representation, illustrating them in information-theoretic terms to explicitly characterize representation in neuroscience.

Mitochondria make essential contributions to neural development. Zhao and colleagues provide an overview of the mechanisms that regulate mitochondrial biogenesis, degradation, remodelling and transport, the importance of these processes for neural development and the proposed links between altered mitochondrial dynamics and neurodevelopmental disorders.

The neuronal circuits that comprise the spinal cord central pattern generator (CPG) orchestrate the rhythmic and coordinated motor activity that underlies locomotion. El Manira describes recent advances in our understanding of the organization and operation of the CPG, highlighting findings that have revealed its distributed, modular and adaptable nature.

Brain activity in regions traditionally linked to social cognition in primates also supports analogous computational demands in non-social contexts. In this Perspective, Mahmoodi and Rushworth examine the computations required to navigate the social lives of human and non-human primates, arguing how shared neural mechanisms carrying out similar computations in non-social contexts indicate computational rather than contextual specialization in the ‘social brain’.

Guidance is lacking on how to best integrate sex, gender and social and structural determinants of health into neuroscience research on brain resilience in ageing and dementia. In this Roadmap article, Rajah et al. propose a way forward for conducting more inclusive research in this field.

The dynamic and versatile architecture of the neuronal endoplasmic reticulum (ER) enables it to support a wide range of functions. In this Review, Carvalhais, Kole and Kuijpers describe the mechanisms that shape ER morphology and its contributions to specific local functions within neuronal subcellular domains.

Connectome reconstructions across multiple species reveal that the morphology of axonal projections is highly variable, even between neurons of the same location or subtype. In this Review, Richards et al. discuss the implications of this for interareal communication and for functional network plasticity in both the healthy brain and following brain injury.

Recent evidence suggests that astrocytes, through coordinated activation in sparse ensembles, contribute to memory traces — termed ‘astro-neuronal engrams’. In this Perspective, Sánchez Romero and Navarrete discuss supporting evidence for astro-neuronal engrams and how these findings challenge traditional neurocentric models of memory.

Maladaptive central autonomic remodelling that occurs in response to heart failure and hypertension drives sympathetic overactivity and cardiac dysfunction. In this Review, van Weperen and Vaseghi discuss the neural, glial and molecular mechanisms underlying these changes, as well as emerging neuromodulatory strategies aimed at restoring autonomic balance.

Neural decoding remains constrained by methods that miss the brain’s chemical signalling dimension. In this Review, Kim and Park discuss hybrid and transformative neurochemical interfaces that provide real-time access to the brain’s dynamic molecular activity.

Connectomics has delivered on its promise to map neuronal circuits at scale and at synaptic resolution. In this Review, Helmstaedter describes recent methodological achievements and remaining challenges in synaptic-resolution connectomics while synthesizing expanding connectomic mapping ambitions that include resolving local circuits of larger brains and screening of connectomes.

The thermosensory system across insects and mammals has shared principles of neuronal wiring and encoding. In this Review, Carta, Vestergaard and Poulet discuss how the nervous systems of insects and mammals process the thermal information that underlies thermal perception.

Both localized and distributed views on the functional organization of the brain have been put forward. In this Perspective, Rosen and Freedman examine the degree to which these two views account for abstract cognition.

Artificial intelligence is rapidly advancing our mechanistic understanding of the shared structure between the brain and higher-order behaviours. In this Review, Mathis and Mathis synthesize state-of-the-art methods in joint modelling of neural activity and behaviour, emphasizing both the technical innovations and the conceptual frameworks driving progress in this rapidly evolving field.

The importance of peripheral immunity in Alzheimer disease has gained much traction in recent years, mainly due to multiple genome-wide association studies identifying risk loci associated with genes expressed predominantly in the periphery. This review discusses the importance of peripheral immune cells in shaping brain physiology and their role in Alzheimer disease.

Methodological shortcomings have constrained studies describing the complex dynamics of interpersonal coordination, which is essential to human sociality. In this Perspective, Chidichimo et al. advance the case for the formal introduction of information-theoretic quantities and methods to overcome existing limitations in studies of naturalistic human interactions.

In this Review, Saef Izzy and colleagues examine the therapeutic potential of stem cells in stroke, with a focus on neural and mesenchymal stem cells. They explore how these stem cells interact with brain immune cells to modulate the inflammatory microenvironment, restore blood–brain barrier integrity and promote tissue repair following a stroke.

Programmed axon degeneration (PAxD) is activated by axotomy to execute the self-destruction of a severed distal axon. It may also be activated by some non-axotomy insults, suggesting it has a role in some neurodegenerative diseases. Here, Loreto and Neukomm review the molecular mechanisms of PAxD, its involvement in disease and its potential as a therapeutic target.