Reviews & Analysis

Enhancers of endocannabinoid signaling are potential analgesics, but they cause unacceptable psychiatric side effects. A new study reports an inhibitor of endocannabinoid breakdown that has analgesic activity and cannot enter the CNS.

Stress primes the hypothalamic-pituitary-adrenal axis response to subsequent stressors. A new study finds that acute stress modifies the properties of excitatory synapses impinging on parvocellular neurons of the paraventricular nucleus.

Variation in neuronal properties is often thought of as noise that interferes with information processing. A study now suggests that neuronal diversity may actually improve the coding capacity of neural ensembles.

This review discusses the promises and pitfalls of animal models of psychiatric illnesses such as schizophrenia, bipolar disorder and depression. The authors propose guidelines for reporting and interpreting results from such models.

A new study examines the contribution of DNA methylation to long-term behavioral and morphological changes produced by cocaine exposure or chronic social defeat stress.

Two studies in this issue show that the protein MeCP2, which is implicated in Rett syndrome, also critically regulates behavioral responses to psychostimulants. Although the two studies highlight different mechanisms of MeCP2 in regulating these behaviors, both underscore the importance of epigenetic mechanisms in establishing drug addiction.

A study in this issue finds that under conditions of intense activity at specific inhibitory synapses, the voltage gated Cl⁻ channel CIC-2 is vital for allowing efflux of accumulated internal Cl⁻.

An examination of the micro-organization of visual cortex using two-photon calcium imaging provides a new level of insight into retinotopic maps, finding that retinotopy is scrambled on fine scales in mouse primary visual cortex.

How do we estimate the duration of a temporal interval in a familiar context? A new study finds that it is appropriate, perhaps even advantageous, to tolerate a small bias in our estimate to reduce the overall temporal uncertainty.

A study shows that spatial learning is accompanied by the reorganization of place fields of hippocampal CA1 neurons, and that this reorganization is subsequently reactivated in an NMDA-dependent manner for memory consolidation.

Narrowing down the genetic basis of Down syndrome, in which hundreds of genes are triplicated, has been difficult. A new study finds that the expression of two affected genes, Olig1 and Olig2, is critical for maintaining the balance of inhibitory and excitatory signaling in a mouse model of Down syndrome.

A new study finds that neurons in the ferret frontal cortex typically respond to sound only during trained auditory tasks and that these neurons depict the task-related meaning rather than the acoustical properties of stimuli.

A study reports a new method for wholesale labeling of neuronal proteins in situ that can visualize newly synthesized protein in a manner compatible with standard immunostaining techniques.

Melanocortin signaling in the CNS, which crucially regulates feeding and energy expenditure, also regulates the expression of a hepatic cholesterol re-uptake receptor. Thus, the brain in rodents directly controls the levels of circulating high-density cholesterol species. The relevance to human cholesterol metabolism remains unknown.

Acupuncture entails stimulating discrete points on the body with needles to alleviate pain. A study in this issue finds that local activation of adenosine A₁ receptors in mice contributes to the anti-nociceptive effects of acupuncture.

High Na⁺ channel density is thought to underlie the axon initial segment's (AIS's) low action potential initiation threshold, but a new study estimates functional Na⁺ channel density in the AIS is only threefold higher than in the soma.

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.