Reviews & Analysis

Cell-surface receptors of the Dscam family are required for neuronal wiring inDrosophila. Schmucker discusses the homophilic-binding specificity and diversity of these receptors, their potential role in different aspects of neuronal wiring and key questions that remain unanswered.

Membrane phosphoinositides are important for generating key intracellular second messengers and are also able to directly regulate the activity of membrane proteins. Gamper and Shapiro discuss the regulatory actions of phosphoinositides on a range of neuronal ion channels and transporters.

Semantic memory is thought to be structured as a widely distributed brain network that contains information regarding modality-specific features. Here, Patterson and colleagues discuss the idea, based on neuropsychological and neuroimaging data and connectionist modelling, that conceptual knowledge also requires an amodal hub.

Darwin saw the evolution of the vertebrate eye as one of the biggest challenges for his theory. Lamb and colleagues integrate molecular and morphological evidence across different taxa and propose a sequence of evolutionary steps through which the vertebrate eye might have emerged.

It has become apparent that, in addition to removing excess extracellular glutamate, glutamate transporters can help to shape synaptic events. Tzingounis and Wadiche review the structural properties and regulation of glutamate transporters, highlighting their diverse roles in key brain regions.

Post-translational protein modification can modulate neuronal activity and function. Here, Henley and colleagues discuss the emerging data on the roles of protein SUMOylation in various aspects of nervous-system function and in the pathology of several neurological disorders.

Chemokines were discovered as cytokines that have chemotactic properties. They are receiving renewed attention, this time from neuroscientists, owing to the possibility that they might act as neurotransmitters or neuromodulators. In a provocative Opinion article, Rostène and colleages review the evidence for this possibility.

Drugs of abuse alter synaptic plasticity mechanisms in key brain circuits. Kauer and Malenka review the drug-induced synaptic modifications that take place in the mesolimbic dopamine system, which is central to reward processing and contributes to addiction.

During vertebrate development a transcription factor 'code' specifies the identity of motor neurons. In this article, Sarah Guthrie reviews the latest findings on the differentiation programmes of cranial motor neurons and highlights the importance of diffusible axon guidance molecules for the correct navigation of these neurons to the muscles that control the head and neck.

Debate continues regarding the neural substrates of recollection and familiarity, the two components of recognition memory. Squire and colleagues review the data and provide a new perspective, arguing against a neuroanatomical separation of these processes in the medial temporal lobe.

For some genes, the two alleles are differentially expressed depending on whether they are inherited from the mother or the father. Wilkinson and colleagues review how this intriguing phenomenon plays a part in brain development and function.

Alternative splicing generates much of the protein diversity that is required for many aspects of nervous system development and function. Black and colleagues describe the roles of alternative splicing in the nervous system and the mechanisms by which splicing is regulated.

The ability of retinoic acid to reactivate developmental programmes in the adult suggests that it could be important for the induction of regeneration and the treatment of neurodegenerative disorders. In this Review, Malcolm Maden discusses the roles of retinoic acid in the developing and mature nervous system, highlighting its potential therapeutic applications.

Nitric oxide (NO) has multiple physiological functions in the nervous system. Calabreseet al. focus on the neuroprotective and neurotoxic effects of NO and, based on our understanding of NO-mediated pathways, list potential therapeutic strategies for the prevention and treatment of neurodegenerative diseases.

Many neurons show daily rhythms in gene expression and electrical activity. Erik Herzog discusses the molecular and cellular events that underlie this rhythmicity, and shows how the robustness and plasticity of the circadian system allow the brain to adapt to environmental conditions.

Local protein synthesis in dendrites is thought to contribute to local changes in synaptic activity during development and learning. Bramham and Wells review what is known about the regulation of dendritic mRNAs and their function in activity-dependent plasticity.

The development of neuroprotective drugs has been hampered by the fact that many drugs interfere with normal brain functions. Stuart Lipton describes strategies for drug development that are based on the principle that drugs should interact with their target only during states of pathological activation.

Lipids function as both structural membrane components and signalling molecules. Piomelli and colleagues review the implications of lipids in neuronal function, discuss the technical challenges in the field and highlight the potential roles of lipid-mediated retrograde signalling at central synapses.

Several recent studies have indicated that common neural substrates are involved in remembering past events and imagining future events. Schacter and colleagues outline these findings and discuss the theoretical implications for our understanding of the adaptive functions of memory.

The subventricular zone (SVZ) is the major source of proliferative cells in the adult brain. In this Review, Curtis, Faull and Eriksson describe how the SVZ responds to neurodegenerative disease and discuss possible therapeutic strategies to harness its neurogenic potential.