Reviews & Analysis

Central nervous system (CNS) neurons and glial cells are generated by both direct and indirect neurogenesis. In this Review, Thor outlines the landscape of indirect neurogenesis during CNS development in key species, including humans, and describes the main genetic mechanisms that contribute to its region-specific, neural progenitor cell-specific and temporal control.

There are a number of models that have attempted to explain why people with Parkinson disease move slowly. In this Perspective, Williams identifies the inconsistencies in these models and suggests that these may be addressed by a different model that considers disordered information transmission as fundamental to slow movement development.

The prefrontal cortex is critical for working memory, over a timescale of seconds. In this Review, Miller and Constantinidis examine how the prefrontal cortex facilitates the integration of memory systems across other timescales as well. In this framework of prefrontal learning, short-term memory and long-term memory interact to serve goal-directed behaviour.

Recent advances in the development of gene therapy tools provide hope that these approaches might modulate the altered gene expression that characterizes many CNS disorders. Gao et al. provide an overview of current gene therapy strategies, highlighting the interdependence of therapeutic modality, delivery vehicle and administration route for translational success.

The detection, discrimination and categorization of odours are essential for survival across the animal kingdom. In this Review, Datta and co-workers describe and compare the neural circuits that mediate the processing of olfactory information and the key principles of olfactory coding in insects and mammals.

Slowing neurodegeneration is the most pressing clinical need for multiple sclerosis (MS). In this Review, Woo, Engler and Friese provide a neuron-centric view on inflammation-induced neurodegeneration in MS and discuss key pathways and molecules that can be therapeutically targeted.

At early developmental stages, spontaneous activity in the mammalian cortex is characterized by the occurrence of highly synchronous network events. Portera-Cailliau and colleagues describe these activity patterns, their underlying mechanisms and function, and their transition to the desynchronized activity observed in adult individuals.

A clinically viable speech neuroprosthesis could restore natural speech to individuals with vocal-tract paralysis. In this Review, Silva et al. discuss rapid progress in neural interfaces and computational algorithms for decoding speech from cortical activity and propose evaluation metrics to help standardize speech neuroprostheses.

The location-specific firing of hippocampal place cells changes when an animal enters a new environment, a phenomenon known as ‘remapping’. In this Perspective, André A. Fenton challenges standard models of place cell remapping and proposes a key role for the ‘re-registration’ of internally organized place cell population dynamics in the encoding of distinct environments.

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.