Volume 14 Issue 12, December 2011

Reward signals are widespread in the brain, but why? A study now identifies an important difference in the reward signals encoded by the neurons in the primate anterior cingulate and orbitofrontal cortices during decision making, suggesting that reward-related activity in these areas is shaped by different contextual factors.

Orchestration of gene expression enables coordination between the nucleus and synapses. A report now uncovers a function for the fragile X mental retardation protein in RNA editing necessary for synaptic development.

A study now reports the genome-wide profiling of 5-hydroxymethylcytosine, an alternate epigenetic state of DNA modification, of the mouse brain across development, aging and in a neurodevelopmental disease model.

Variations in the arginine vasopressin receptor gene, AVPR1A, are shown to be associated with pain sensitivity in a stress- and sex-specific manner in both mice and men.

This review addresses the issues that attend gene discovery in autism spectrum disorders (ASDs). It summarizes recent findings in human genetics and their relevance to models of pathology, highlights the issues raised by the apparent convergence of ASD genetic risks with distinct psychiatric disorders, and considers the interaction of neurobiology and genetics in our understanding of social disability syndromes.

Reversal learning requires cognitive flexibility and is mediated by multiple brain regions, including the prefrontal cortex and the dorsal striatum. This study examines how environmental factors such as stress can affect prefrontal cortex–dorsal striatum interactions and reversal learning.

Deficits in prefrontal cholinergic function have been implicated in cognitive impairment in many neuropsychiatric diseases. Here, the authors report that monkeys with lesions of cholinergic input to prefrontal cortex were impaired on a spatial working memory task, but not on other tests of cognitive function that also require intact prefrontal cortex.

In this behavioral study, the authors demonstrate how increased attention can sometimes lead to lower subject confidence, leading subjects to become more conservative in making decisions during a visual perception task.

Loss of FMR1 gene function results in fragile X syndrome. Here, the authors demonstrate that the Drosophila fragile X homolog dFMR1 is involved in the RNA editing pathway via interaction with the enzyme dADAR and suggest that proper NMJ synaptic architecture requires modulation of dADAR activity by dFMR1.

Polarization of a neuron begins with the appearance of the first neurite. The authors study Drosophila neurons in vivo and find that the mechanisms of polarization appear to be defined at the precursor stage.

The authors show that the Drosophila gustatory receptor Gr64e is necessary and sufficient for neuronal and behavioral response to glycerol. They find that species of Drosophila that are predicted to carry pseudogenes of Gr64e have reduced glycerol sensitivity.

The authors report that, in the extended amygdala, 2-arachidonoylglycerol and anandamide mediate retrograde short-term depression and long-term depression, respectively, via different signaling pathways. In contrast, in the striatum, 2-arachidonoylglycerol and cannabinoid receptor 1–mediated retrograde signaling mediated both forms of plasticity.

The authors report that GABA transporter 1 (GAT-1) cation currents directly increase GABAergic neuronal excitability and synaptic GABA release in the periaqueductal gray (PAG), and that these GAT-1 changes contribute to PAG-mediated signs of opioid withdrawal.

The authors show that synapses between rod bipolar cells and AII amacrine cells in the retina can encode luminance and compute contrast in the sustained and transient components of vesicle release, respectively. A release/replenishment model shows that a single, homogenous pool of vesicles is sufficient to generate this behavior.

The authors developed an assay using optogenetic stimulation of dopaminergic neurons as a reference stimulus to measure the reward value of nutrients. They found that fasting increases and leptin decreases the reward value of sucrose.

The authors find that the Avpr1a gene, encoding the vasopressin-1A receptor, is responsible for strain-dependent pain sensitivity of mice to formalin and capsaicin. In humans, a single nucleotide polymorphism in AVPR1A was found to affect capsaicin pain and desmopressin analgesia. In both species, the effects were male specific and dependent on stress levels at the time of testing.

Patches in primary visual cortex (V1) rich in cytochrome oxidase were thought to contain unoriented, color-opponent neurons. Here the authors measure orientation tuning in V1 neurons using acutely implanted 100-electrode arrays. Patch cells were nearly as well tuned as those in interpatches, suggesting that processing of form and color is not strictly segregated in primate V1. Patch cells had higher mean discharge rates, consistent with their enhanced metabolism.

This study reports a double dissociation in the neuronal correlates of value-based decision making in monkey prefrontal cortex, with orbitofrontal cortex neurons encoding choice value relative to recent choice values, while anterior cingulate cortex neurons flexibly encode multiple decision parameters and reward prediction errors using a 'common valuation currency'.

The orbitofrontal cortex (OFC) has been hypothesized to carry information regarding the value of expected rewards. Such information could be used for generating instructive error signals conveyed by dopamine neurons. Here the authors report that this is indeed the case. However, contrary to the simplest hypothesis, OFC lesions did not result in the loss of all value information. Instead, lesions caused the loss of value information derived from model-based representations.

This technical report describes a 360-channel flexible multi-electrode array with high spatial resolution, wide coverage area and minimal damage to the recorded neural tissue. Among other descriptions of multiunit in vivo neuronal recording in cats, the authors also use the electrode array to show spiral-patterned spread of epileptic neural activity in the neocortex.

DNA methylation in the context of epigenetics occurs on the 5' position of cytosine, which can be further oxidized by enzymes from the Ten-eleven translocation (Tet) family, resulting in 5-hydroxymethylcytosine (5-hmC). In the context of embryonic stem cells, Tet and 5-hmC DNA act in an alternate epigenetic state that regulates epigenetic programming and stem cell differentiation. Here, the authors describe the epigenomic profiling of 5-hmC in mouse and human brain across different time periods during development and aging.