Volume 18 Issue 7, July 2015

Epidemiological studies and anecdotal evidence show overlap between psychiatric disorders and creativity, but why? A new study uses genome-wide association data from schizophrenia and bipolar disorder to show that genetics are part of the explanation.

Discovering the environmental factors that control microglia is key to understanding and managing brain health. A new study finds that microbiota in the gut are essential to the regulation of microglial maturation and activation.

Schizophrenia-linked single nucleotide polymorphisms in MIR137 alter expression of miR-137 in neurons. Abnormal expression of miR-137 affects vesicle release at presynaptic terminals and in turn alters hippocampal functioning.

In a bidirectional relationship, the sleep/wake cycle regulates amyloid-β (Aβ) levels and Aβ accumulation then disrupts sleep. A quantitative three-way model now suggests that Aβ impairs memory via its effect on sleep.

In this Review, Schneggenburger and Rosenmund discuss the molecular mechanisms that control the Ca²⁺ dependence of synaptic vesicle fusion during spontaneous and evoked modes of release at mammalian brain synapses. They argue that the same pool of vesicles is recruited during spontaneous and evoked release but at drastically different rates.

This Review article by Baljit Khakh and Michael Sofroniew discusses the latest progress in demonstration of molecular, cellular and functional heterogeneity of astrocytes in the central nervous system. The article highlights the way in which this diversity within and across astrocytes can affect normal function of the brain differently, and discusses pathological conditions where astrocyte heterogeneity is instrumental in manifesting various aspects of CNS dysfunction.

Genetic risk scores derived from GWAS of psychotic disorders are greater in creative professionals unaffected by psychosis. This association cannot be explained by shared environment or education. Thus, a shared genetic architecture underlies the propensity for creativity and psychosis.

This study shows that ocular dominance plasticity (ODP) is accompanied by changes to DNA methylation at specific genes in the mouse visual cortex. The authors also show that pharmacological inhibition of the DNA methylation process can alter the functional consequence of ODP.

Gancarz et al. identify Activin-receptor signaling—including the downstream transcription factor Smad3—as an intracellular signaling pathway that is regulated in the nucleus accumbens following abstinence from cocaine. The authors demonstrate that altering Activin-receptor signaling bi-directionally regulates relapse behavior and dendritic spine plasticity.

Chronic social stress has adverse behavioral consequences and can result in the development of depression in humans. Using a rodent social stress model, we report increased synaptic connectivity between the thalamus and striatum in susceptible mice that controls behavioral coping mechanisms relevant to depression.

In this study, the authors show that host microbiota play a key role in modulating microglia homeostasis. Germ-free mice or mice with only limited microbiota complexity displayed defects in microglial cell proportions and maturation, leading to impaired innate immune responses. The authors find that short-chain fatty acid signaling regulates these effects in vivo.

Zhao et al. report that brain vessels have a major role in clearing Alzheimer's disease–related toxin Aβ from brain and show that PICALM gene product and its variant associated with an increased risk for Alzheimer's disease inactivate an Aβ clearance system in blood vessels, leading to Aβ brain accumulation and cognitive impairment.

The Q390X mutation in the GABA_A receptor GABRG2 has been associated with Dravet syndrome in humans. In this study, the authors generated a new genetic epileptic encephalopathy animal model, the Gabrg2^+/Q390X knock-in mouse, and show that expression of this mutant protein leads to seizures, chronic accumulation and aggregation of mutant subunit protein and age-dependent neurodegeneration.

Neurexins are essential presynaptic cell-adhesion molecules whose biological significance is poorly understood. Here, the authors interrogate Nrxn3 function in two brain regions, using two types of preparations and in three mutant mouse lines, and find that Nrxn3 plays mechanistically distinct, brain region-specific functions to regulate either presynaptic release or AMPA receptor stability.

Neurodevelopmental disorders are frequently associated with synaptic dysfunction. Recent genome-wide association studies associate the gene encoding microRNA-137 with an increased risk for schizophrenia. Using mouse and human models, the authors show that dysregulation of this miRNA leads to presynaptic defects and, consequently, to impaired synaptic plasticity and cognitive dysfunction.

The authors showed that mGluR5 can upregulate the expression of ΔFosB, a resilience molecule, in the nucleus accumbens. In stress-induced animal models of depression, mGluR5-induced upregulation of ΔFosB in the nucleus accumbens enhances resilience to stress.

How motor cortical activity relates to muscle movement is still unclear. Here the authors trained neural networks to reproduce muscle activity of reaching monkeys. The optimal solutions produced by these networks resembled the single-neuron and population level neural activity seen in the motor cortex of the same monkeys.

The cortical activity patterns associated with individual finger movements are highly variable across participants, with each person showing a distinct "cortical fingerprint". The idiosyncratic representations are subject to an invariant organization principle: the overlap between activation patterns is tightly shaped by how frequently fingers move together in everyday life.

The authors show that memory-selective neurons in the human medial temporal lobe signal memory retrieval confidence. Using a balance-of-evidence model, the authors demonstrate that the signals provided by these neurons are sufficient to determine the choice certainty of declarative memory-based decision in single trials.

The mechanisms through which β-amyloid impairs human memory remain unclear. This study shows that regional-specific β-amyloid load in cognitively normal older adults impairs NREM slow wave oscillations, thereby compromising overnight hippocampus-dependent memory consolidation. NREM sleep disruption therefore represents a novel mechanistic pathway through which β-amyloid contributes to hippocampus-dependent memory dysfunction in later life.