Impaired reversal learning in the Dlg2+/- rat model of genetic risk for psychiatric disorder: Important questions regarding the neuro-behavioral mechanisms of reversal learning.

In this issue, Griesius et al report that heterozygous Dlg2+/- rats showed a reversal learning impairment on a specific bowl-digging task, whereas other reversal tasks were unaffected. The study suggests that Dlg2 gene disruption, which has been linked to neuropsychiatric disorders, including schizophrenia, may cause relatively specific impairments in reversal learning, an important aspect of cognitive flexibility. The study draws attention to two important issues regarding the neuro-behavioral mechanisms of reversal learning, namely that hippocampal dysfunction, which is prominent in Dlg2+/- rats, may contribute to reversal learning impairments and that, depending on the task and previous experience, brain and behavioral mechanisms of reversal learning may differ.

Improved cognitive performance in trace amine-associated receptor 5 (TAAR5) knock-out mice.

Trace amine-associated receptors (TAARs) are a family of G protein-coupled receptors present in mammals in the brain and several peripheral organs. Apart from its olfactory role, TAAR5 is expressed in the major limbic brain areas and regulates brain serotonin functions and emotional behaviours. However, most of its functions remain undiscovered.

Activity Subspaces in Medial Prefrontal Cortex Distinguish States of the World.

Medial prefrontal cortex (mPfC) activity represents information about the state of the world, including present behavior, such as decisions, and the immediate past, such as short-term memory. Unknown is whether information about different states of the world are represented in the same mPfC neural population and, if so, how they are kept distinct. To address this, we analyze here mPfC population activity of male rats learning rules in a Y-maze, with self-initiated choice trials to an arm end followed by a self-paced return during the intertrial interval (ITI).

Spectral estimation for detecting low-dimensional structure in networks using arbitrary null models.

Discovering low-dimensional structure in real-world networks requires a suitable null model that defines the absence of meaningful structure. Here we introduce a spectral approach for detecting a network's low-dimensional structure, and the nodes that participate in it, using any null model. We use generative models to estimate the expected eigenvalue distribution under a specified null model, and then detect where the data network's eigenspectra exceed the estimated bounds.

An ensemble code in medial prefrontal cortex links prior events to outcomes during learning.

The prefrontal cortex is implicated in learning the rules of an environment through trial and error. But it is unclear how such learning is related to the prefrontal cortex's role in short-term memory. Here we ask if the encoding of short-term memory in prefrontal cortex is used by rats learning decision rules in a Y-maze task.

The after-hours circadian mutant has reduced phenotypic plasticity in behaviors at multiple timescales and in sleep homeostasis.

Circadian clock is known to adapt to environmental changes and can significantly influence cognitive and physiological functions. In this work, we report specific behavioral, cognitive, and sleep homeostatic defects in the after hours (Afh) circadian mouse mutant, which is characterized by lengthened circadian period. We found that the circadian timing irregularities in Afh mice resulted in higher interval timing uncertainty and suboptimal decisions due to incapability of processing probabilities.

Working-for-Food Behaviors: A Preclinical Study in Prader-Willi Mutant Mice.

Abnormal feeding behavior is one of the main symptoms of Prader-Willi syndrome (PWS). By studying a PWS mouse mutant line, which carries a paternally inherited deletion of the small nucleolar RNA 116 (Snord116), we observed significant changes in working-for-food behavioral responses at various timescales. In particular, we report that PWS mutant mice show a significant delay compared to wild-type littermate controls in responding to both hour-scale and seconds-to-minutes-scale time intervals.

The Zfhx3-Mediated Axis Regulates Sleep and Interval Timing in Mice.

An AT motif-dependent axis, modulated by the transcription factor Zfhx3, influences the circadian clock in mice. In particular, gain of function of Zfhx3 significantly shortens circadian rhythms and alters the transcriptional activity of an important class of neuropeptides that controls intercellular signaling in the suprachiasmatic nucleus (SCN) of the hypothalamus. The ZFHX3/AT axis revealed an important, largely cell-nonautonomous control of the circadian clock.

Deletion of the Snord116/SNORD116 Alters Sleep in Mice and Patients with Prader-Willi Syndrome.

Study Objectives: Sleep-wake disturbances are often reported in Prader-Willi syndrome (PWS), a rare neurodevelopmental syndrome that is associated with paternally-expressed genomic imprinting defects within the human chromosome region 15q11-13. One of the candidate genes, prevalently expressed in the brain, is the small nucleolar ribonucleic acid-116 (SNORD116). Here we conducted a translational study into the sleep abnormalities of PWS, testing the hypothesis that SNORD116 is responsible for sleep defects that characterize the syndrome.

TAAR1 Modulates Cortical Glutamate NMDA Receptor Function.

Trace Amine-Associated Receptor 1 (TAAR1) is a G protein-coupled receptor expressed in the mammalian brain and known to influence subcortical monoaminergic transmission. Monoamines, such as dopamine, also play an important role within the prefrontal cortex (PFC) circuitry, which is critically involved in high-o5rder cognitive processes. TAAR1-selective ligands have shown potential antipsychotic, antidepressant, and pro-cognitive effects in experimental animal models; however, it remains unclear whether TAAR1 can affect PFC-related processes and functions.

Dominant β-catenin mutations cause intellectual disability with recognizable syndromic features.

The recent identification of multiple dominant mutations in the gene encoding β-catenin in both humans and mice has enabled exploration of the molecular and cellular basis of β-catenin function in cognitive impairment. In humans, β-catenin mutations that cause a spectrum of neurodevelopmental disorders have been identified. We identified de novo β-catenin mutations in patients with intellectual disability, carefully characterized their phenotypes, and were able to define a recognizable intellectual disability syndrome.

Dynamics of action potential firing in electrically connected striatal fast-spiking interneurons.

Fast-spiking interneurons (FSIs) play a central role in organizing the output of striatal neural circuits, yet functional interactions between these cells are still largely unknown. Here we investigated the interplay of action potential (AP) firing between electrically connected pairs of identified FSIs in mouse striatal slices. In addition to a loose coordination of firing activity mediated by membrane potential coupling, gap junctions (GJ) induced a frequency-dependent inhibition of spike discharge in coupled cells.

Division protein interaction web: identification of a phylogenetically conserved common interactome between Streptococcus pneumoniae and Escherichia coli.

The ability of each of the 11 Streptococcus pneumoniae division proteins to interact with itself and with each of the remaining proteins was studied in 66 combinations of protein pairs, using a bacterial two-hybrid system. Interactions (homo- or hetero-dimerizations) were detected between 37 protein pairs, whereas 29 protein pairs did not interact. In some cases, positive interactions of the S.