Volume 15 Issue 6, June 2012

By bringing mGluR1/5 and proline-directed kinases together, the scaffold protein Preso1 stabilizes the interaction between mGluR1/5 and Homer. This mechanism may attenuate calcium influx into spinal neurons and reduce pain.

How do outcomes affect future behavior? A study using precise optogenetic stimulation finds that learning from positive reinforcement is mediated by striatal pathways distinct from those that mediate learning from punishment.

A long-standing puzzle has been the seeming inconsistency between neuronal responses in primary visual cortex to colored stimuli and the elementary perceptual attributes of color vision. Nonlinear analysis resolves this paradox.

As long-awaited advances in psychiatric genetics begin to materialize in force, promising to steer us safely to the best of times in psychiatric disease research, many pharmaceutical companies pull away from the challenge of drug development, threatening to bring us to the worst of times for the field. There is a real danger of missed opportunities and a sense of urgency for defining a clear path forward.

Using high-fidelity imaging of pHluorin-tagged vesicular monoamine transporter 2, the authors report differences in coupling of calcium entry and exocytosis between different populations of dopamine neurons. In ventral tegmental area neurons, exocytosis is controlled by calbindin-D28k, and this maintains a lower vesicular release probability as compared with substantia nigra neurons.

Cell type–specific expression and activation of channelrhodopsin-2 in the dorsomedial striatum shows that stimulation of dopamine D1 receptor–expressing direct pathway medium spiny neurons (MSNs) can reinforce operant behavior in awake behaving mice, whereas activation of D2 receptor–expressing indirect pathway MSNs punishes operant behavior.

In this study, the authors show that TopBP1 is critical for preventing replication-induced DNA damage accumulation in early-born neural progenitors, thereby maintaining genomic integrity in these cells.

In addition to their function in gene regulation, certain microRNAs can be secreted by cells. Here, the authors show that the microRNA let-7 can cause neurodegeneration by directly activating Toll-like receptor 7 and that individuals with Alzheimer's disease have more let-7b in their cerebrospinal fluid.

The authors show that Preso1 acts as a scaffolding protein that binds mGluR, Homer and proline-directed kinases. Deletion of Preso1 prevents phosphorylation of mGluR at the Homer binding site and leads to an increase in mGluR5-dependent inflammatory pain.

Phosphorylation and SUMOylation of the kainate receptor (KAR) subunit GluK2 have both individually been shown to regulate KAR surface expression. Here the authors find that KAR synaptic plasticity and transmission are regulated by the dynamic interaction of GluK2 phosphorylation and SUMOylation.

The authors studied AMPAR-mediated currents in cerebellar stellate cells from stargazer mice, which lack the prototypical TARP stargazin (γ-2). They report that calcium-permeable AMPARS can localize at synapses in the absence of stargazin; moreover, mEPSCs mediated by TARPless AMPARs were also detected in these cells following knockdown of their only other TARP, γ-7.

The authors show that conditioned medium from human mesenchymal stem cells reduces functional deficits in an animal model of multiple sclerosis and promotes the development of oligodendrocytes and neurons. They identify hepatocyte growth factor and its receptor cMet as critical for this effect.

The authors find that the Fic domain–containing protein Fic is necessary for vision in Drosophila. Fic expression is required in the capitate projections of glial cells, where it may be involved in histamine recycling, thus supporting neurotransmission in photoreceptors.

Exposure to rival males increases mating duration in Drosophila melanogaster. The authors show that visual stimuli are sufficient to induce longer mating duration (LMD). LMD requires the circadian clock genes timeless and period, and involves visual memory circuits and a subset of pigment dispersing factor–expressing neurons in the circadian circuit.

This study uses a new analysis method for magnetoencephalography measurements of the human brain to show brain-wide and frequency-specific functional coupling of spontaneous oscillatory activities during resting state.

Repeated exposure to cocaine increases dendritic spine density on nucleus accumbens (NAc) neurons. Here the authors show that the small GTPase Rac1 is necessary and sufficient for cocaine-induced behavior and spine changes in NAc neurons, adding support for a causal role for structural plasticity in cocaine-induced behavior.

Using optogenetic activation of adult-born neurons in the mouse olfactory bulb, the authors find that selective stimulation of new interneurons generated during adulthood, but not earlier, accelerates learning in a two-odor discrimination task and improves olfactory memory.

It has generally been thought that the primary visual cortex (V1) receives its driving input via the lateral geniculate nucleus and is modulated by input from the lateral pulvinar nucleus. Using several different techniques to manipulate lateral pulvinar activity, the authors report that the lateral pulvinar is able to gate information outflow from V1.

Understanding color vision requires knowing how signals from the cone photoreceptors are combined in the cortex. Here the authors record from V1 neurons while an automated system identified stimuli that differed in cone contrast, but evoked the same response. They report that many V1 neurons combine cone signals nonlinearly and provide a new framework for color processing in V1.

Impulsivity is a multi-dimensional construct, and it is plausible that distinct brain networks contribute to its different aspects. Here the authors identify distinct cortical and subcortical networks underlying cognitive, clinical and genetic dimensions of impulsivity in a large sample of adolescents.