Reviews & Analysis

Many cognitive functions rely on the ability to link distinct but related memories, while retaining the capacity to recall the individual details of the linked memories. Inokuchi and colleagues describe evidence that memory linking involves engram overlap and discuss the mechanisms that regulate this process.

The developmental colonization of the brain by microglial progenitors and establishment of microglial cell identity set the stage for microglial function in the adult. Barry-Carroll and Gomez-Nicola describe the mechanisms that regulate the development of microglia, including their origins, infiltration and colonization of the brain, proliferation and fate determination.

Many brain areas support complex language processing behaviours. In this Review, Fedorenko et al. disentangle the ‘core’ language system as functionally distinct from the perceptual and motor brain areas and knowledge and reasoning systems it closely interacts with during language comprehension and production.

Parkinson disease (PD) has been linked to dysfunction in a number of key intracellular signalling pathways that contribute to disease pathology. Coukos and Krainc describe the physiological functions of a selection of PD-linked proteins and their convergent effects on mitochondrial, lysosomal and synaptic dysfunction in PD.

Pathological compulsive behaviour is a potential transdiagnostic symptom of several neuropsychiatric disorders. In this Review, Robbins et al. examine the psychological basis of compulsions and compulsivity and their underlying neural circuitry, focused on fronto-striatal systems implicated in goal-directed behaviour and habits.

Selective vulnerability of particular neuronal cell types is a characteristic of neurodegenerative diseases. Martin Kampmann explores our current understanding of the cellular and molecular mechanisms that lead to selective vulnerability in different diseases.

There is a pressing need for drugs that effectively control pharmaco-resistant seizures and prevent their generation. In this Review, Vezzani and co-workers discuss the interconnected roles of mTOR signalling and neuroinflammatory processes in epileptogenesis, and how targeting these pathways might prove useful therapeutically.

How does motor-cortex activity well before movement not drive motor outputs? In this Review, Churchland and Shenoy detail how searching for answers transitioned the understanding of neural activity during movement from single-neuron tuning towards population-level factors and revealed an essential computational role of output-null factors.

Sleep is an active state during which the synaptic connections that form memories are remodelled. In this Perspective, Wassing and colleagues discuss how failures in sleep-dependent adaptation to emotionally distressing experiences might be a key contributor to post-traumatic stress disorder and related conditions.

Altered network activity during sleep is observed in some individuals with Alzheimer disease and in mouse models of the disorder. In this Perspective, Inna Slutsky proposes that hyperexcitability and sleep disturbances in Alzheimer disease result from disruption of the mechanisms that maintain activity homeostasis in the brain.

Sub-additive responses to simultaneously presented stimuli and quenching of variability in responses to repeated presentations of a stimulus are characteristics of neurons in the primary visual cortex. In this Perspective, Goris et al. argue that these phenomena often co-occur and may have common mechanistic and computational origins.

Exposure to acute and long-term exposure to cold temperatures results in the activation of thermoregulatory mechanisms that are under CNS control. In this Review, Mota and Madden discuss long-term physiological adaptations to cold exposure, with an emphasis on the specific states of hibernation, torpor and obesity.

A direct influence of light exposure on cognition and behaviour, beyond that associated with circadian rhythms, has been reported. Mahoney and Schmidt consider the evidence for light’s effects on aspects of cognitive neurobehavioural performance, summarize current understanding of the underlying cellular and circuit mechanisms and point to future directions for this field of research.

Animals frequently engage in curiosity-related behaviours that appear to provide them with no immediate benefits. Monosov discusses the neural circuits in the primate brain that are involved in these non-instrumental information-seeking behaviours, focusing on those that mediate the exploration of novel objects and the pursuit of information to reduce future uncertainties.

During adolescence, we acquire skills and behavioural patterns that support our future survival through goal-directed learning. Wilbrecht and Davidow describe the neural and cognitive systems that support goal-directed learning in adolescence, as well as our growing understanding of the influence of context on this process.

‘Mechanism’ is a frequently used causal concept in neuroscience but can have different meanings that are often not specified. In this Review, Ross and Bassett explore these different meanings and the challenges associated with the variable usage of this term before discussing how these challenges may be met.

Within the CNS, APOE4 — a risk factor for late-onset Alzheimer disease — is produced by a variety of cell types. Blumenfeld, Yip, Kim and Huang discuss recent scientific advances that have begun to unravel the cell type-specific roles of APOE4 and outline a corresponding cell type-specific APOE4 cascade model of Alzheimer disease.

Data-driven disease progression models are computational tools that infer long-term disease timelines from short-term biomarker data and may provide insights into disease processes. In this Review, Young, Oxtoby et al. provide an overview of such models, with a focus on how they have been used in the context of neurodegenerative diseases, notably Alzheimer disease.

Synaptic engineering involves the synthetic insertion of new synapses between neurons in vivo. In this Perspective, Rabinowitch, Colón-Ramos and Krieg explore this emerging approach for studying neural circuits, describing the different methods that have been used and how they have been implemented.

SARS-CoV-2 infection is associated with various neurological effects both during and after infection. In this Review, Meinhardt and colleagues discuss the possible impact of SARS-CoV-2 infection on different cell populations of the nervous system and the neurological alterations that result, thus facilitating the development of treatment options.