Reviews & Analysis

The conservation of processes associated with normal ageing across species suggests that model systems can contribute to our understanding of human brain ageing. In this Perspective article the authors review the insights into longevity emerging from model organisms and highlight the need for the new paradigms in gerontology to be applied to the CNS.

The experience of social rejection, exclusion or loss is often described as 'painful'. Naomi Eisenberger here outlines the evidence that the processing of these forms of 'social pain' share many underlying neural substrates with physical pain mechanisms and considers the implications of this convergent neural circuitry.

A growing body of evidence suggests that many psychiatric illnesses are associated with impaired mitochondrial function. Manji and colleagues review evidence from studies in animal models and humans and discuss strategies for therapeutics aimed at enhancing mitochondrial function in patients with psychiatric disorders.

Local mRNA translation provides an efficient mechanism by which highly polarized cells such as neurons can respond to extrinsic signals. Holt and colleagues describe the growing evidence for the importance of local axonal mRNA translation and protein synthesis in various aspects of nervous system development and function.

On the basis of data from brain network science, Bullmore and Sporns propose that brain organization is shaped by an economical trade-off between minimizing wiring cost and maximizing the efficiency of information transfer between neuronal populations and discuss this idea in the context of psychiatric and neurological disorders.

Optogenetics enables the precise and targeted manipulation of the activity of specific neurons and is a powerful tool for the dissection of neural circuits. Tye and Deisseroth describe the latest refinements in optogenetic technology and show how this approach is being used to investigate the circuits involved in psychiatric and neurological disorders.

The brain is a major target of insulin and insulin-like growth factors (IGFs). Fernandez and Torres-Alemán describe how these peptides enter the CNS to reach specific brain areas and review their actions in the developing and adult brain. They propose that insulin and IGFs regulate diverse processes that are all ultimately involved in energy homeostasis.

A growing field of research aims to examine the potential overlap between the characteristics and underlying mechanisms of drug addiction and obesity. Here, Fletcher and colleagues argue that there is not yet sufficient evidence to support a 'food addiction' model and call for caution in the application of this model to clinical and policy recommendations.

Normal ageing is associated with impairments in cognitive function, including memory, and with specific and relatively subtle synaptic alterations in the hippocampus and prefrontal cortex. The authors describe these structural changes reported in monkeys and rodents, how they might affect age-associated cognitive decline and potential strategies to limit their impact.

Dysfunction of the circadian clock contributes to the age-associated decline of brain functions. Here, the authors examine the evidence for this link and the potential underlying molecular mechanisms such as the circadian control of brain metabolism and hormone secretion.

Hypothermia has neuroprotective effects in certain clinical conditions and in animal models of brain insult. Yenari and Han review the mechanisms that underlie these effects. Focusing on animal models of ischaemia, they describe how cooling influences multiple aspects of brain physiology in the acute, subacute and chronic stages of ischaemia.

In recent decades, advances in technology have enabled the structure of the nervous system to be dissected in greater detail than ever before. In this Opinion article, Denk and colleagues outline why structural information is so important for our understanding of the function of neural circuits and describe new tools and approaches that are improving the structural information that we can acquire.

Adult mammalian CNS axons show little regenerative capacity following injury, in part because they fail to assemble functional growth cones at their tips. However, axons from the mammalian peripheral nervous system and non-mammalian species show more regenerative potential. Here, Bradkeet al. examine the process of growth cone assembly after axonal injury. Understanding why this process does not always succeed may facilitate the development of treatments for CNS-damage-related disability.

Long-term potentiation (LTP) describes the long-lasting increase in the strength of synaptic transmission between two neurons, a process that may be integral to learning and memory. In this Review, Lisman and colleagues examine the central role that calcium/calmodulin-dependent protein kinase II (CaMKII) has in this form of synaptic plasticity. Focusing on postsynaptic mechanisms, the authors discuss CaMKII in the context of both the early and late stages of LTP.

There is increasing evidence of widespread Ca²⁺waves and localized spark-like events in neurons, particularly in dendrites; however, their origin and function is still poorly understood. This article reviews emerging data on the nature of these signals, their spatial distribution and potential roles.

Processing within neural circuits in the retina extracts information about the direction of motion of images projected onto the retina. Vaney and colleagues describe the cellular components of this circuitry and outline our current understanding of the mechanisms that are involved in generating direction-selective responses in the retina.

The notion that the disruption of inhibitory circuits might underlie certain clinical features — notably cognitive impairment — in various neuropsychiatric disorders, including schizophrenia and autism, is receiving considerable attention. Focusing heavily on studies in animal models, Oscar Marín reviews the evidence indicating that the basis of such disruption is linked to specific defects in interneuron development and function.

The neurotransmitters expressed by neurons were thought to be fixed, but recent evidence suggests that during development, and also in the mature nervous system, neurotransmitter expression can be respecified by activity. This respecification seems to have a homeostatic role at synapses and influences behaviour.

Cognition results from large-scale interactions among widely distributed brain regions. Siegel and colleagues review studies showing that these interactions are reflected by correlated neuronal oscillations. They propose that correlated oscillations in large-scale cortical networks may be 'fingerprints' of canonical neuronal computations underlying cognitive processes.

The distribution of mitochondria to regions of the neuron that have the greatest requirement for ATP supply maintenance and sequestration of Ca²⁺is essential for neuronal function. Sheng and Cai describe the molecular mechanisms regulating mitochondrial transport in neurons and discuss its contribution to aspects of neuronal function.