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  • Antidepressant treatments are often selected on a trial-and-error basis, resulting in limited average treatment efficacy. Florian Holsboer argues that combining pharmacogenetic data with biomarkers identified using genomics, proteomics, metabolomics, neuroimaging and neuroendocrinological studies might lead to personalized antidepressant medications with superior efficacy and fewer adverse effects.

    • Florian Holsboer
  • A growing field of neuroscience aims to understand how immune responses can promote CNS repair. Popovich and Longbrake discuss current approaches to manipulate neuroimmune interactions and give their opinion on the challenges ahead.

    • Phillip G. Popovich
    • Erin E. Longbrake
  • In recent years the role of the cerebellum in the control of non-motor functions has been acknowledged. Here, Ito elaborates on his hypothesis of internal-model control of mental functions and describes recent findings that provide supporting evidence for the theory.

    • Masao Ito
  • Neuroscientists often refer to brain areas as being 'affective' or 'cognitive'. In this Opinion article, Luiz Pessoa argues that complex behaviours are based on dynamic coalitions of brain networks and that there are no specifically 'affective' or 'cognitive' brain areas.

    • Luiz Pessoa
  • The hippocampus has an undisputed role in memory and has been key in discovering synaptic plasticity as the basis for learning. Bliss and colleagues provide an update on unresolved problems that surround LTP and memory, and propose strategies for finding answers that centre on new technologies.

    • Guilherme Neves
    • Sam F. Cooke
    • Tim V. P. Bliss
  • 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.

    • William Rostène
    • Patrick Kitabgi
    • Stéphane Mélik Parsadaniantz
  • 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.

    • Stuart A. Lipton
  • Many neuroscientists are motivated by the hope that their research will ultimately benefit people with neurological and mental disorders. Steven Hyman asks whether neuroscience has progressed to the point that the diagnostic manuals for mental disorders can usefully incorporate its findings.

    • Steven E. Hyman
  • The mechanisms underlying the effects of repetitive transcranial magnetic stimulation (rTMS) are unclear. Ridding and Rothwell argue that a better understanding of these mechanisms and the conditions for which rTMS is used will reveal whether rTMS offers true therapeutic potential.

    • Michael C. Ridding
    • John C. Rothwell
  • It is widely accepted that adult neurogenesis occurs in the hippocampus and olfactory bulb in the mammalian brain, but whether it is restricted to these areas remains controversial. Gould discusses evidence for and against neocortical neurogenesis in the adult, emphasizing some key methodological issues.

    • Elizabeth Gould
  • Decades of research have not yet succeeded in definitively characterizing the neuroanatomy of speech processing. Hickok and Poeppel describe a dual-stream model of speech processing and discuss how this model can account for some of the field's paradoxical findings.

    • Gregory Hickok
    • David Poeppel
  • Loss of aligned glial pathways may contribute to the inability of axons to successfully regenerate following CNS injury. Raisman and Li discuss why transplantation of olfactory ensheathing cells might be a promising strategy to re-establish these pathways and restore function.

    • Geoffrey Raisman
    • Ying Li
  • 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.

    • Peter Redgrave
    • Kevin Gurney
  • 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.

    • Sidney A. Simon
    • Ivan E. de Araujo
    • Miguel A. L. Nicolelis
  • 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.

    • Andreas Meyer-Lindenberg
    • Daniel R. Weinberger
  • 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.

    • Elizabeth J. Bradbury
    • Stephen B. McMahon
  • 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.

    • Avshalom Caspi
    • Terrie E. Moffitt
  • 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.

    • Arvind Govindarajan
    • Raymond J. Kelleher
    • Susumu Tonegawa