Reviews & Analysis

Lipid rafts — specialized plasma membrane microdomains that are thought to regulate various signalling events — are the focus of intensive research into their roles in the nervous system. Here, Rasenick and colleagues review the evidence for their involvement in regulating neurotransmitter signalling.

Emerging evidence implicates members of a recently identified class of regulatory molecules, microRNAs, as having important roles in nervous system development and function. Kenneth Kosik reviews these findings and discusses the future challenges facing the field.

SLO channels comprise a family of high-conductance potassium channels with several distinctive features that give them the versatility to function in various cellular contexts. The authors describe the key properties and physiological roles of these channels in the nervous system.

Brain atlases have existed for centuries; however, these traditional atlases have many limitations, which promise to be overcome with new brain imaging techniques. Toga and colleagues highlight exciting advances in brain mapping technology and the ongoing progress towards integrative multimodal atlases.

Understanding the pathophysiological mechanisms that underlies neurological dysfunction in multiple sclerosis is essential for effective therapeutic intervention. Waxman reviews the evidence that aberrant Na⁺channel expression contributes to restoration of axonal conduction, axonal injury and cerebellar dysfunction in multiple sclerosis.

The cadherin superfamily has roles in the development and organization of complex neuronal circuits. Takeichi explores the evidence from invertebrate and vertebrate studies for the involvement in these processes of different cadherin subfamilies, including classic cadherins, Flamingo/CELSRs and the protocadherins.

The phasic dopamine response is traditionally thought to signal reward prediction errors. Redgrave and Gurney evaluate evidence from studies of basal ganglia circuitry and signal timing, and propose instead that the short-latency dopamine signal is important for discovering novel actions.

Mirror neurons are specialized cells that fire both when an animal performs an action and when it observes others performing that action. A role for these cells in social cognition is emerging, and their dysfunction is now implicated in autism.

The gustatory system is crucial for detecting and discriminating between foods and selecting nutritious diets. Simon and colleagues now propose that this system achieves its complex tasks through distributed neural codes that represent the sensory and postingestive properties of tastants.

Development of sensory epithelia in the inner ear involves the progressive restriction of epithelial progenitors to give rise to specific types of hair or supporting cells. Kelley reviews current knowledge about the factors that regulate these cell fate decisions.

Phantom limb pain frequently occurs following limb amputation or deafferentiation. Emerging evidence suggests that in addition to peripheral changes, plasticity in the CNS has an important role in the pathophysiological mechanisms of phantom pain, highlighting potential targets for therapeutic interventions.

A common apolipoprotein E (APOE) isoform confers risk for Alzheimer's disease. New evidence that APOE, cholesterol, reelin and APOE receptors are vital for synaptic plasticity in the adult brain might help to unravel some key pathological mechanisms in neurodegenerative disorders.

An enormous expansion in cortical surface area was crucial for the evolution of the primate gyrencephalic cortex. Kriegstein and colleagues evaluate models of progenitor cell division that might underlie cortical expansion during development and provide an insight into this evolutionary step.

Macular degeneration is a principal cause of visual loss in the Western world. Advances in imaging technologies, the identification of genes and the development of animal models are now paving the way for new therapeutic strategies for this disorder.

The role of sonic hedgehog as a morphogen involved in establishing ventral cell identity in the CNS is well known. Fishell and colleagues outline the current understanding of the molecular pathways involved in patterning and describe several recently identified and unrelated roles for hedgehog signalling.

Cancer induces pain, which often leads to the diagnosis of disease. Mantyh discusses how understanding the mechanisms involved in cancer pain and chemotherapy-induced sensory neuropathy, also associated with pain, might improve the survival and quality of life of cancer patients.

Voltage-gated ion channels are traditionally considered to solely mediate ion flux. New evidence is emerging that these channels also have important roles in various biological processes that are independent of ion conduction, including neuronal signalling, cell adhesion and gene transcription.

An important pathological feature of polyglutamine repeat diseases involves abnormal interactions between the mutant protein and histone-modifying enzymes, leading to transcriptional dysregulation. Inhibition of these enzymes is therefore a promising therapeutic strategy for Huntington's disease and other polyglutamine repeat disorders.

Using schizophrenia as an example, Meyer-Lindenberg and Weinberger review the effectiveness of the intermediate phenotype concept for characterizing the neural systems affected by risk gene variants, with a view to elucidating mechanistic aspects of brain function implicated in psychiatric disease.

Failure of neural tube closure leads to neural tube defects, such as spina bifida and anencephaly, and has been linked to insufficiency of folate. The genetic and molecular mechanisms that link folate metabolism to neural tube defects are now being unravelled.