A nonoscillatory, millisecond-scale embedding of brain state provides insight into behavior.

The most robust and reliable signatures of brain states are enriched in rhythms between 0.1 and 20 Hz. Here we address the possibility that the fundamental unit of brain state could be at the scale of milliseconds and micrometers.

A non-oscillatory, millisecond-scale embedding of brain state provides insight into behavior.

Sleep and wake are understood to be slow, long-lasting processes that span the entire brain. Brain states correlate with many neurophysiological changes, yet the most robust and reliable signature of state is enriched in rhythms between 0.1 and 20 Hz.

A discrete parasubthalamic nucleus subpopulation plays a critical role in appetite suppression.

Food intake behavior is regulated by a network of appetite-inducing and appetite-suppressing neuronal populations throughout the brain. The parasubthalamic nucleus (PSTN), a relatively unexplored population of neurons in the posterior hypothalamus, has been hypothesized to regulate appetite due to its connectivity with other anorexigenic neuronal populations and because these neurons express Fos, a marker of neuronal activation, following a meal. However, the individual cell types that make up the PSTN are not well characterized, nor are their functional roles in food intake behavior.

MCH Regulates SIRT1/FoxO1 and Reduces POMC Neuronal Activity to Induce Hyperphagia, Adiposity, and Glucose Intolerance.

Melanin-concentrating hormone (MCH) is an important regulator of food intake, glucose metabolism, and adiposity. However, the mechanisms mediating these actions remain largely unknown. We used pharmacological and genetic approaches to show that the sirtuin 1 (SIRT1)/FoxO1 signaling pathway in the hypothalamic arcuate nucleus (ARC) mediates MCH-induced feeding, adiposity, and glucose intolerance.

Need-based prioritization of behavior.

When presented with a choice, organisms need to assimilate internal information with external stimuli and past experiences to rapidly and flexibly optimize decisions on a moment-to-moment basis. We hypothesized that increasing hunger intensity would curb expression of social behaviors such as mating or territorial aggression; we further hypothesized social interactions, reciprocally, would influence food consumption. We assessed competition between these motivations from both perspectives of mice within a resident-intruder paradigm.

Defined Paraventricular Hypothalamic Populations Exhibit Differential Responses to Food Contingent on Caloric State.

Understanding the neural framework behind appetite control is fundamental to developing effective therapies to combat the obesity epidemic. The paraventricular hypothalamus (PVH) is critical for appetite regulation, yet, the real-time, physiological response properties of PVH neurons to nutrients are unknown. Using a combination of fiber photometry, electrophysiology, immunohistochemistry, and neural manipulation strategies, we determined the population dynamics of four molecularly delineated PVH subsets implicated in feeding behavior: glucagon-like peptide 1 receptor (PVH), melanocortin-4 receptor (PVH), oxytocin (PVH), and corticotropin-releasing hormone (PVH).

A GABAergic Projection from the Centromedial Nuclei of the Amygdala to Ventromedial Prefrontal Cortex Modulates Reward Behavior.

Unlabelled: The neural circuitry underlying mammalian reward behaviors involves several distinct nuclei throughout the brain. It is widely accepted that the midbrain dopamine (DA) neurons are critical for the reward-related behaviors. Recent studies have shown that the centromedial nucleus of the amygdala (CeMA) has a distinct role in regulating reward-related behaviors.

Neuroendocrinology: Electromagnetic control of neural activity - prospective physics for physicians.

Rapid, minimally invasive control of explicit neural activity would be a major advance for basic and clinical research in the neuroscience and neuroendocrinology fields, and could have applications for the potential treatment of neurological disorders. A new study by Stanley . brings us closer to this goal.

Spatiotemporal control of opioid signaling and behavior.

Optogenetics is now a widely accepted tool for spatiotemporal manipulation of neuronal activity. However, a majority of optogenetic approaches use binary on/off control schemes. Here, we extend the optogenetic toolset by developing a neuromodulatory approach using a rationale-based design to generate a Gi-coupled, optically sensitive, mu-opioid-like receptor, which we term opto-MOR.

Toxic and non-toxic aggregates from the SBMA and normal forms of androgen receptor have distinct oligomeric structures.

Hormone-dependent aggregation of the androgen receptor (AR) with a polyglutamine (polyQ) stretch amplification (>38) is considered to be the causative agent of the neurodegenerative disorder spinal and bulbar muscular atrophy (SBMA), consistent with related neurodegenerative diseases involving polyQ-extended proteins. In spite of the widespread acceptance of this common causal hypothesis, little attention has been paid to its apparent incompatibility with the observation of AR aggregation in healthy individuals with no polyQ stretch amplification. Here we used atomic force microscopy (AFM) to characterize sub-micrometer scale aggregates of the wild-type (22 glutamines) and the SBMA form (65 glutamines), as well as a polyQ deletion mutant (1 glutamine) and a variant with a normal length polyQ stretch but with a serine to alanine double mutation elsewhere in the protein.

Imperfect interface of Beclin1 coiled-coil domain regulates homodimer and heterodimer formation with Atg14L and UVRAG.

Beclin 1 is a core component of the Class III Phosphatidylinositol 3-Kinase VPS34 complex. The coiled coil domain of Beclin 1 serves as an interaction platform for assembly of distinct Atg14L- and UVRAG-containing complexes to modulate VPS34 activity. Here we report the crystal structure of the coiled coil domain that forms an antiparallel dimer and is rendered metastable by a series of 'imperfect' a-d' pairings at its coiled coil interface.

The Beclin 1-VPS34 complex--at the crossroads of autophagy and beyond.

An increasing body of research on autophagy provides overwhelming evidence for its connection to diverse biological functions and human diseases. Beclin 1, the first mammalian autophagy protein to be described, appears to act as a nexus point between autophagy, endosomal, and perhaps also cell death pathways. Beclin 1 performs these roles as part of a core complex that contains vacuolar sorting protein 34 (VPS34), a class III phosphatidylinositol-3 kinase.

Cell "self-eating" (autophagy) mechanism in Alzheimer's disease.

The autophagy pathway is the major degradation pathway of the cell for long-lived proteins and organelles. Dysfunction of autophagy has been linked to several neurodegenerative disorders that are associated with an accumulation of misfolded protein aggregates. Alzheimer's disease, the most common neurodegenerative disorder, is characterized by 2 aggregate forms, tau tangles and amyloid-beta plaques.

Broiler embryo bone development is influenced by incubator temperature, oxygen concentration and eggshell conductance at the plateau stage in oxygen consumption.

1. Four experiments were conducted to evaluate the effects of temperature (TEM) and oxygen (O(2)) concentrations during the last 4 d of incubation on bone development. Fertile eggs from two strains were obtained that either exhibited Low or High eggshell conductance (G).

Effects of incubator temperature and oxygen concentration during the plateau stage of oxygen consumption on Turkey embryo long bone development.

Temperature (TEM) and O(2) concentrations during the plateau stage of oxygen consumption are known to affect yolk utilization, tissue development, and thyroid metabolism in turkey embryos. Three experiments were conducted to evaluate these incubation effects on long bone development. Fertile eggs of Nicholas turkeys were used.

Specific N-terminal mutations in the human androgen receptor induce cytotoxicity.

Polyglutamine (polyQ) stretch amplification in different proteins causes neurodegenerative disease. These proteins form intracellular aggregates thought to be cytotoxic but differ in pathology and tissue specificity. Here, we demonstrate that specific sequences outside the polyQ stretch of the human androgen receptor contribute to polyQ pathology.

Receptor internalization-independent activation of Smad2 in activin signaling.

Activin, a member of the TGFbeta family of cytokines, signals through heteromeric transmembrane complexes composed of type I and type II Ser/Thr kinase receptors. Activated by type II receptors, the type I receptor phosphorylates, thereby activating its effectors Smad2 and Smad3. It has been shown that the ligand-bound TGFbeta receptors endocytose to early endosomes, where they phosphorylate Smads.

Structural organization and DNA methylation patterning within the mouse L1 family.

We have studied stable differences in patterns of DNA methylation seen in the repeated sequences of mouse cells. A cloned 1330-base pair fragment of mouse repetitive DNA (pFS-13) was used as a probe in Southern blotting experiments. Mouse spleen and L1210 lymphoma DNA appeared to be normally methylated at HpaII sites probed by this sequence.

Primate evolution of a dispersed human repetitive DNA sequence.

A dispersed middle repetitive DNA sequence isolated originally from human chromosome 12 did not show homology with rodent DNA under standard conditions of Southern DNA blot analysis. The evolutionary relationship of this human repetitive DNA to that of other primates was investigated using three hybridization methods: DNA dot blot, Southern DNA blot analysis, and chromosome in situ hybridization. Homology with the human repetitive DNA was found throughout the suborder Anthropoidea, in fourteen ape and New and Old World monkey species.

Chromosome deletion mapping of interspersed low-copy repetitive DNA.

A cloned 2.2 Eco RI segment of interspersed repetitive DNA was hybridized to genomic DNA from a mentally retarded patient with an interstitial deletion in the long arm of one chromosome 12 (12q-). Under hybridization conditions of high stringency, one prominent 2.

Y chromosome length related to fetal loss.

The Y/20 ratio (length of Y chromosome/length of chromosome 20) was examined among 216 males, 108 of whose wives had a history of repeated abortions (study group), and 108 who were mentally retarded (controls). There was no significant difference in frequency of long Y (Y/20 equal to or greater than 1) between the study group and controls. Also, there was the expected male: female ratio among normal living children of couples in the study group, and the Y/20 ratio was not significantly increased among fathers with abnormal male offspring.