Articles in 2014

The authors show that leucine-rich repeat kinase 2 (Lrrk2) binds protein kinase A (PKA) regulatory subunit IIβ to decrease PKA activity in striatal projection neurons (SPNs). Lrrk2 regulation of PKA prevents its synaptic translocation, altering synaptogenesis and transmission in developing SPNs. A Parkinson's disease–associated mutant of Lrrk2 prevented its interaction with PKARIIβ.

This study shows that the memory deficit caused by amyloid fibrils in rodents is mediated, in part, by neuroinflammation leading to histone modification via alteration of the interaction between HDAC2 and methyl-CpG-binding protein 2 (MeCP2) and resulting epigenetic modification of the neuroligin 1 promoter, causing a reduction in neuroligin 1 expression in neurons.

The authors show that mice lacking one copy of gene encoding the transcription factor T-box brain 1 (TBR1) show deficient axonal projections from amygdala neurons, as well as social and cognitive behavioral deficits. Tbr1 haploinsufficiency alters expression of multiple Tbr1 target genes, and restoring their expression restores axon outgrowth defects in vivo.

The authors show that dopamine receptor 1 (D1)-expressing neurons in the medial prefrontal cortex (mPFC) of mice show increased activity in response to food intake. Using optogenetic stimulation and inhibition, they show that mPFC D1 neuron projections to the medial basolateral amygdala can increase or decrease food intake, respectively.

The mechanism behind lateral inhibition that establishes the receptive fields of retinal neurons has remained elusive. Here the authors show that synaptic proton concentration mediates horizontal cell negative feedback in the retina and that this transmission depends on activity of a proton pump and proton-permeant ion channel.

Here the authors report that higher levels of task-relevant motor variability predict faster learning both across individuals and across tasks in two different paradigms and that training can reshape the temporal structure of motor variability, aligning it with the trained task to improve learning. These results support the importance of action exploration, a key idea from reinforcement learning theory.

μ-opioid receptor (MOR) was previously shown to be necessary for opiate reward, analgesia and dependence. To better understand the specific anatomical and cell type loci of MOR action in opiate reward and reinforcement learning, the authors use cell-specific rescue expression of MOR in subtypes of neurons in the mouse brain that lack MOR globally and show that MOR in the striatal direct-pathway medium spiny neurons is sufficient to rescue the reward action of opioids without affecting opioid analgesia or withdrawal in MOR knockout mice.

Inhibition sculpts neural activity through various cell types and circuits, but, unlike excitation, it is not self-propagating and must be locally recruited with a temporal delay. Here the authors show a fast, feedforward inhibitory mechanism that bypasses synaptic delay through ephaptic coupling of an interneuron to the axon initial segment of a projection cell.

Current models of how animals estimate motion involve correlations between pairs of points in space and time. Here the authors show that both fly and human visual systems can encode the direction and contrast polarity of moving edges using three-point correlations, and that this enhances motion estimation accuracy.

The authors show that a nonpsychoactive cannabinoid, DH-CBD, can rescue exaggerated acoustic startle phenotypes caused by startle disease–causing point mutations in the glycine receptor (GlyR) α1 subunit. Homomeric and presynaptic GlyRs showed significant impairment as a result of these mutations, which was selectively rescued by DH-CBD.