Volume 15 Issue 2, February 2012

A study uses light-gated ion channels to control the activity of neurons in each eye, thereby revealing how the timing of neuronal firing dictates whether visual circuits segregate from one another or stay mixed.

Cell specification of olfactory receptor neurons in Drosophila is orchestrated by context-dependent response to Notch signaling mediated by Hamlet, which directs specific chromatin modifications in subsets of neurons.

A knock-in mouse mimicking a MeCP2 mutation found in human Rett syndrome recapitulates disease features, including progressive motor and cognitive impairments—and correlations emerge between MeCP2 dosage in mice and phenotype.

A mathematical model based on the dynamics of molecular signaling pathways predicts an optimal training regimen that enhances learning and memory.

This is a review of current advances in the genetics of substance use disorders (SUDs), discussing how both genetic and environmental sources of risk are required to develop a complete picture of SUD etiology.

The authors report that Rhes, a striatal-specific protein, activates mTOR. Rhes-depleted mice showed reduced dyskinesia, but maintained motor improvement following L-DOPA treatment.

This study uses computational modeling to demonstrate how a visual number sense might emerge. The results of the model successfully predict behavior from both non-human primates and human children.

The authors describe a new approach to glioblastoma multiforme (GBM) therapy using therapeutic stem cells encapsulated in biodegradable synthetic extracellular matrix in mouse models of human GBM resection.

The authors show that the transcription factor UNC-3 acts via a common cis element to regulate the battery of genes that confer cholinergic identity on a subset of motor neurons in the nematode. This study provides further insight into the mechanisms by which the coordination of genetic programs acts to specify neuronal subtypes.

In the striatum, direct pathway and indirect pathway medium spiny neurons (MSNs) receive both cortical and thalamic projections in an intermingled fashion. This study shows that a known axonal repulsive cue system—semaphorin 3E and its receptor Plexin-D1—acts as a determinant of thalamostriatal synapse development, specifically for direct pathway MSNs where presynaptic axons express the ligand and the receptor signals in the postsynaptic MSN target.

This study shows a new molecular mechanism governing olfactory receptor neuron (ORN) subtype diversification from a shared precursor cell. Selection of ORNs in Drosophila is mediated by Notch signaling. Chromatin modifications directed to specific genes targeted by Notch modify the responses to this signal and diversify ORN identity and circuitry.

In this study, the authors show that NAB-1 acts during synaptogenesis to link the F-actin network and the active zone proteins SYD-1 and SYD-2, thereby promoting presynapse assembly in Caenorhabditis elegans.

This study demonstrates a direct role for synaptotagmin I in the endocytosis of synaptic vesicles that is distinct from its role in exocytosis. In addition, the authors find that either of the C2 domains of syt1 can act as a calcium sensor during endocytosis.

Here, the authors show that chronic blockade of neuronal activity reduces the connectivity of recurrent CA3-CA3 neurons in the rodent hippocampus while the synaptic strength of the remaining recurrent connections increased approximately twofold. They also show that this homeostatic process is mediated by the changes in presynaptic release probability regulated by cyclin-dependent kinase 5.

The authors show that in rodents, NRG1-induced activation of ErbB4 in parvalbumin-expressing inhibitory interneurons may serve as a critical endogenous negative-feedback mechanism to suppress limbic epileptogenesis.

In mouse models, the authors find that NRG1–ErbB4 signaling contributes to epilepsy through regulating the excitability of fast-spiking parvalbumin interneurons. ErbB4 expression was also reduced in human epileptogenic tissue.

Rett syndrome (RTT) is caused by mutations in MeCP2. This study describes a new line of knock-in mutant mice that mimics a MeCP2 mutation found in individuals with RTT and recapitulates RTT-like phenotypes, including motor and cognitive impairments. These MeCP2 knock-in mice also have age-dependent abnormalities in audiogenic event-related neuronal information processing.

In a mouse model of cannabinoid tolerance, persistent activation of the eCB pathway impairs eCB-mediated long-term depression (LTD) preferentially at connections to striatopallidal neurons. This is associated with a shift in behavioral control from goal-directed action to habitual responding; both LTD and behavioral changes were rescued by modulating small-conductance Ca²⁺-activated K⁺ channels (SK channels).

The authors use computational modeling to design an optimized learning protocol that takes into account the precise timing of molecular signaling cascades that are necessary for synaptic facilitation. This study demonstrates how learning and memory can be enhanced by the coordination of biochemical mechanisms and training protocols.

Development of eye-specific segregation and binocularity in the superior colliculus, dorsal lateral geniculate nucleus and primary visual cortex is partly attributed to the timing of spontaneous retinal waves, in which bursts of activity are thought to act through a Hebbian learning rule to guide circuit refinement. This study uses the latest optogenetic tools to provide definitive evidence for the binocular activity timing rule—and the specific temporal features of activity—in dictating binocularity development in the mouse visual system.

The mediodorsal thalamus links the medial prefrontal cortex and the amygdala in associative learning process in primates. Using mouse models, this study finds that the dual firing modes of mediodorsal thalamus neurons, tonic and bursting, have opposite effects on fear extinction.

Neurons in the prefrontal cortex (PFC) and parietal cortex, including the lateral intraparietal area (LIP), can represent the category membership of stimuli. Category signals in LIP were thought to result from top-down feedback from the PFC. Here the authors show that category signals in the LIP are stronger, more reliable and occur earlier than those in the PFC.

The authors show that structural connectivity, as measured by diffusion-weighted imaging, can predict functional activation to faces in the fusiform gyrus. The structure–function correspondence developed in one group of subjects outperformed two other predictive models and was able to predict activation in a second group of subjects.

This study describes a microinjection technique that allows for the acute manipulation of individual neural stem cells in organotypic slice cultures via direct delivery of biologically active molecules.