Reviews & Analysis

Mutations in proteins essential for certain cellular processes have been implicated in motor neuron degeneration in ALS. Pasinelli and Brown review how genetic analyses of these effects are unravelling the diverse molecular pathways involved in ALS pathogenesis.

Enhanced novelty and complexity in the environment can have impressive effects on experience-dependent plasticity under normal conditions. Moreover, such enriched environments can delay the onset and progression of a range of CNS disorders, with important implications for therapeutic strategies.

The ability to directly image alterations in brain function has been highly influential for cognitive neuroscience. Functional MRI is now emerging as a promising clinical tool for informing diagnosis and therapy for a range of disorders of the nervous system.

Interneurons are a diverse set of neurons that comprise various morphological, physiological and chemical characteristics. Recent work has shed light on the origins and specification of distinct subtypes of cortical interneurons, which could drive new discoveries on cortical function.

There is no known cure for spinal cord injury, although numerous promising cellular, molecular and rehabilitative strategies are being tested in animal models and clinical trials. Emerging findings suggest that a combination of therapies will lead to optimal functional outcome.

During development, precisely coordinated processes allow the formation of complex neural circuitry, but after CNS injury in adult mammals, functional circuits fail to reform. Recent work indicates that the recapitulation of developmental processes will be advantageous for successful functional recovery.

The human left and right hemispheres have distinct functions. Sun and Walsh discuss recent genetic, imaging and neurological studies in an attempt to unravel the molecular mechanisms of brain asymmetry and handedness and to understand their evolutionary underpinning.

Mammals keep track of relative position and orientation by integrating self-motion cues. McNaughton and colleagues discuss the neurobiological evidence for a synaptic matrix capable of performing this task, and propose a model for how this neuronal network might arise developmentally.

Glial inhibition — involving myelin inhibitors and astroglial scarring — represents one of the major barriers to regeneration after CNS injury. Knowledge of the molecular mechanisms of these processes could be crucial for developing therapies to promote axon regeneration and plasticity.

Although potential therapeutic strategies for spinal cord injury are emerging, the mechanisms underlying functional recovery are unclear. Recent work emphasizes the contribution of axon regeneration and plasticity, yet their involvement, and that of less well-explored processes, remains to be established.

Many neuronal and network behaviours are surprisingly stable in the face of ongoing fluctuations in channels and receptors. The authors discuss issues relevant to the homeostatic regulation of synaptic and intrinsic currents necessary for stable neuronal and network activity.

Recent evidence suggests that the primate cerebellum contributes not only to motor control, but also to higher cognitive function. Ramnani suggests that the uniform cellular organization of the cerebellum enables established models for motor information processing to be extended to information processing of a far more abstract nature.

The appropriate targeting of voltage-gated ion channels is essential for the normal functioning of neurons. Lai and Jan review the mechanisms involved in the trafficking and retention of these channels, and discuss how their localization affects neuronal activity.

Itch and pain are distinct sensations processed by different but overlapping neural pathways. Ikomaet al. review recent evidence on the molecular mechanisms that underlie itch sensation, highlighting the complex interaction with pain processing, and discuss the therapeutic implications.

In mental health, the perennial debate about nature versus nurture is giving way to an appreciation that nature and nurture work together. Caspi and Moffitt discuss the opportunities and challenges in the collaboration between psychiatry, epidemiology and neuroscience, and our understanding of gene-environment interactions.

To understand and decode human consciousness is the holy grail in cognitive neuroscience. Haynes and Rees review emerging approaches to reconstruct mental states from non-invasive measurements of brain activity in humans, and discuss the practical and ethical implications.

Long-term memory formation is associated with bidirectional changes in synaptic strength that require enhanced protein synthesis. Govindarajan, Kelleher and Tonegawa describe a model by which translation-dependent plasticity at synapses that are clustered in a dendritic branch facilitates the formation of long-term memory engrams.

Purinergic signalling is one of the most pervasive mechanisms of intercellular communication in the nervous system. Fields and Burnstock review the history and recent development of neuron–glia signalling and the important role of extracellular ATP in these interactions.

Misgeld and Kerschensteiner review howin vivooptical imaging techniques can be used to study the aetiology and therapeutics of neurological disorders. They discuss the challenges of integrating real-time observations with the molecular mechanisms and clinical manifestation of neurological diseases.

Recent work has shed light on how goal-directed actions are transformed into habitual responses. Yin and Knowlton outline a framework for our understanding of habit formation based on behavioural studies and the anatomy and physiology of the basal ganglia circuitry.