Perspectives

Multiple sclerosis is a debilitating inflammatory demyelinating disease of the CNS. In this perspective, the author examines the strengths and weaknesses of the numerous animal models that are currently being used to analyze the pathogenesis of this disease with an eye toward the precise pathological aspect that each model recapitulates.

Neuropathic pain often results from trauma or insult to peripheral nerves. In this Perspective, the authors examine recent evidence that implicates the microglia-expressed purinergic receptor P2X4 in the induction of neuropathic pain and suggest that this pathway marks a spinal mechanism distinct from those that mediate acute or inflammatory pain.

In this perspective, the authors review new developments that suggest that many diseases share features with prion infections. They also highlight some of the critical open questions in prion biology, including how prions damage their hosts and how hosts attempt to neutralize invading prions.

Although the relationship between social factors and physical health outcomes is well-recognized, the modulatory role of neural processing in this link is less well understood. This perspective describes the way in which neurophysiological processes respond to social connection and disconnection to influence health outcomes.

This review discusses how social factors modulate risks for mental disorders, and the neural systems that implement this modulation.

In this perspective, the authors critically evaluate the research on the neural systems supporting empathy.

This perspective describes how neural oscillations are likely to play an important role in speech processing, particularly in creating a discrete neural code.

This perspective discusses newly discovered mechanisms leading to cellular ionic imbalances, as well as underappreciated signaling cascades that mediate cell death and that may add to the traditional glutamatergic mechanisms to which ischemic brain injury is ascribed. An integrated consideration of such new mechanisms may aid in formulating better therapies.

There remains an urgent need to develop new strategies and therapies to help protect the brain from ischemic cell death. In this perspective, the authors suggest that learning more about the mechanisms that underlie brain self-preservation and developing multifaceted approaches that act on multiple pathways involved in both cell death and neuroprotection may advance our efforts to treat stroke.

The authors analyze a large corpus of the neuroscience literature and demonstrate that nearly half of the published studies considered incorrectly compared effect sizes by comparing their significance levels.

The immediate early gene product Arc has been broadly implicated in synaptic and experience-dependent plasticity. In this perspective, the authors synthesize disparate views of Arc in molecular signaling and its relevance to neurological disorders.

Parietal cortex has been implicated as a locus for decision making, and it has been suggested that decision encoding in this area is based on the movement used to report the decision. Here the authors discuss a complementary view that decisions represent more abstract information not linked to movements per se.

Progress in neural recording techniques has allowed the number of simultaneously recorded neurons to double approximately every 7 years, mimicking Moore's law. Emerging data analysis techniques should consider both the computational costs and the potential for more accurate models associated with this exponential growth of the number of recorded neurons.

Experimental work suggests that synaptic and intrinsic neuronal properties vary considerably across identified neurons in different animals. The authors propose that instead of building a single model that captures the average behavior of a neuron or circuit, one could construct a population of models with different underlying structure and similar behaviors, as a way of investigating compensatory mechanisms that contribute to neuron and network function.

This Perspective discusses concepts in endocannabinoid signaling that have come to light with the recent development of pharmacological and genetic tools for the study of biosynthetic enzymes. It also highlights caveats for interpreting data, given the cross-talk between biosynthetic pathways, and outlines future directions for the field.

Disruption of DNA methylation in the brain can impair learning and memory in rodents. In this Perspective, Day and Sweatt provide an overview of evidence that implicates this epigenetic mechanism in memory processes and discuss how past controversies can be explained in light of recent findings.

This perspective discusses the role of epigenetic mechanisms in regulating circadian rhythms, and emphasizes that the role of peripheral machinery is key for a fuller understanding of this regulation.

A genome-wide association study (GWAS) allows for unbiased discovery of genetic bases for various diseases in both familial and sporadic forms. Using two recent GWASs of Alzheimer's disease and Parkinson's disease as examples, Wood and Gandhi discuss the underlying principles of the GWAS and highlight the progress of these studies of neurodegenerative disease and the road lying ahead.

Spinal muscular atrophy (SMA) is a form of childhood neurodegenerative disease due to the lack of SMA protein in motor neurons. This Perspective article discusses the recent progress in our understanding of pathological mechanisms, past efforts in SMA therapy developments, and future directions for translational research.

Przedborski and Wichterle discuss various ways in which stem cells may be used to facilitate research in neurodegeneration. Particularly, this Perspective highlights the use of induced pluripotent stem cells derived from affected individuals as a potential tool to better dissect disease mechanism of neurodegenerative diseases and to aid in restorative therapy.