Temporal relations between peripheral and central arousals in good and poor sleepers.

Good sleepers and patients with insomnia symptoms (poor sleepers) were tracked with two measures of arousal; conventional polysomnography (PSG) for electroencephalogram (EEG) assessed cortical arousals, and a peripheral arterial tonometry device was used for the detection of peripheral nervous system (PNS) arousals associated with vasoconstrictions. The relationship between central (cortical) and peripheral (autonomic) arousals was examined by evaluating their close temporal dynamics. Cortical arousals almost invariably were preceded and followed by peripheral activations, while large peripheral autonomic arousals were followed by cortical arousals only half of the time.

Immunofluorescent Verification of Silencing Estrogen Receptor α with siRNA in the Intact Rodent Brain.

The ability to silence the expression of gene products in a chemically, spatially, and temporally specific manner in the brains of animals has enabled key breakthroughs in the field of behavioral neuroscience. Using this technique, estrogen receptor alpha (ERα) has been specifically implicated in a multitude of behaviors in mice, including sexual, aggressive, locomotor, and maternal behaviors, in a variety of brain regions, including the medial preoptic area, ventromedial hypothalamus, and amygdala. In this chapter, we describe the techniques involved in the generation of the small hairpin RNAs (shRNAs) specifically designed to silence ERα, the construction of the adeno-associated viral (AAV) vector for delivery of the shRNA, the procedures to confirm the silencing of ERα (in vitro and in vivo) and in vivo delivery of the shRNAs to the brains of animals.

Kv2.1 expression in giant reticular neurons of the postnatal mouse brain.

Previous experiments charted the development of behavioral arousal in postnatal mice. From Postnatal Day 3 (P3) to Postnatal Day 6 (P6) mice (a) become significantly more active, "arousable"; and (b) in large reticular neurons, nucleus gigantocellularis (NGC), patch clamp recordings reveal a significantly increased ability to fire high frequency trains of action potentials as are associated with elevated cortical arousal. These action potential trains depend on delayed rectifiers such as Kv2.

Potassium channels and the development of arousal-relevant action potential trains in primary hindbrain neurons.

Neurons in nucleus gigantocellularis (NGC) have been shown by many lines of evidence to be important for regulating generalized CNS arousal. Our previous study on mouse pups suggested that the development of NGC neurons' capability to fire action potential (AP) trains may both lead to the development of behavioral arousal and may itself depend on an increase in delayed rectifier currents. Here with whole-cell patch clamp we studied delayed rectifier currents in two stages.

Fish as a model in social neuroscience: conservation and diversity in the social brain network.

Mechanisms for fish social behaviours involve a social brain network (SBN) which is evolutionarily conserved among vertebrates. However, considerable diversity is observed in the actual behaviour patterns amongst nearly 30000 fish species. The huge variation found in socio-sexual behaviours and strategies is likely generated by a morphologically and genetically well-conserved small forebrain system.

Equation representing the dark-entrained transition from inaction to action in male and female mice.

The activation of behaviour in a daily rhythm governed by the light cycle is a universal phenomenon among humans, laboratory mammals and other vertebrates. For mice, the active period is during the dark. We have quantified the increase in activity when the lights shut off (Light to Dark, L to D) using a generalized CNS arousal assay with 20 ms resolution, rather than traditional running wheels.

Triphenyl phosphate permeates the blood brain barrier and induces neurotoxicity in mouse brain.

Concerns have been raised over the neurotoxicity of triphenyl phosphate (TPP), but there have been few studies of the neurotoxic effects of TPP on mammals and the underlying mechanisms. In this study, weaned male mice (C57/BL6) were used and exposed to 0, 50, or 150 mg/kg TPP daily by oral gavage for 30 days. The blood brain barrier (BBB) permeability of TPP and its metabolite diphenyl phosphate (DPP) in the brain, and TPP induced metabolomic and transcriptomic changes of the brain were investigated.

Sexual motivation: problem solved and new problems introduced.

Background During the past 50 years, motivational studies have evolved from the logical inference of logically required "intervening variables" to explain behavioral change, to electrophysiological and molecular analyses of the mechanisms causing such changes. Aim The purpose of this review article is two-fold: first to describe the logic of sexual motivation in a way that applies to laboratory animals as well as humans, and the second is to address some of the problems of sexual motivation experienced by men. Results When problems of motivational mechanisms are stripped down to their essentials, as performed in the laboratory animal models and are available for reductionistic studies, then the problems can be solved with certainty, as illustrated in the first part of this review.

Maternal diabetes induces autism-like behavior by hyperglycemia-mediated persistent oxidative stress and suppression of superoxide dismutase 2.

Epidemiological studies show that maternal diabetes is associated with an increased risk of autism spectrum disorders (ASDs), although the detailed mechanisms remain unclear. The present study aims to investigate the potential effect of maternal diabetes on autism-like behavior in offspring. The results of in vitro study showed that transient hyperglycemia induces persistent reactive oxygen species (ROS) generation with suppressed superoxide dismutase 2 (SOD2) expression.

Hindbrain V2a Neurons Pattern Rhythmic Activity of Motor Neurons in a Reticulospinal Coculture.

As the capacity to isolate distinct neuronal cell types has advanced over the past several decades, new two- and three-dimensional models of the interactions between different brain regions have expanded our understanding of human neurobiology and the origins of disease. These cultures develop distinctive patterns of activity, but the extent that these patterns are determined by the molecular identity of individual cell types versus the specific pattern of network connectivity is unclear. To address the question of how individual cell types interact , we developed a simplified culture using two excitatory neuronal subtypes known to participate in the reticulospinal circuit: HB9 spinal motor neurons and Chx10 hindbrain V2a neurons.

Mechanisms for the Approach/Avoidance Decision Applied to Autism.

As a neurodevelopmental disorder with serious lifelong consequences, autism has received considerable attention from neuroscientists and geneticists. We present a hypothesis of mechanisms plausibly affected during brain development in autism, based on neural pathways that are associated with social behavior and connect the prefrontal cortex (PFC) to the basal ganglia (BG). We consider failure of social approach in autism as a special case of imbalance in the fundamental dichotomy between behavioral approach and avoidance.

Tinbergen's challenge for the neuroscience of behavior.

Nobel laureate Nikolaas Tinbergen provided clear criteria for declaring a neuroscience problem solved, criteria which despite the passage of more than 50 years and vastly expanded neuroscience tool kits remain applicable today. Tinbergen said for neuroscientists to claim that a behavior is understood, they must correspondingly understand its () development and its () mechanisms and its () function and its () evolution. Now, all four of these domains represent hotbeds of current experimental work, each using arrays of new techniques which overlap only partly.

The Feasibility of Encapsulated Embryonic Medullary Reticular Cells to Grow and Differentiate Into Neurons in Functionalized Gelatin-Based Hydrogels.

The study of the behavior of embryonic neurons in controlled conditions require methodologies that take advantage of advanced tissue engineering approaches to replicate elements of the developing brain extracellular matrix. We report here a series of experiments that explore the potential of photo-polymerized gelatin hydrogels to culture primary embryonic neurons. We employed large medullary reticular neurons whose activity is essential for brain arousal as well as a library of gelatin hydrogels that span a range of mechanical properties, inclusion of brain-mimetic hyaluronic acid, and adhesion peptides.

Molecular profiling of reticular gigantocellularis neurons indicates that eNOS modulates environmentally dependent levels of arousal.

Neurons of the medullary reticular nucleus gigantocellularis (NGC) and their targets have recently been a focus of research on mechanisms supporting generalized CNS arousal (GA) required for proper cognitive functions. Using the retro-TRAP method, we characterized transcripts enriched in NGC neurons which have projections to the thalamus. The unique expression and activation of the endothelial nitric oxide (eNOS) signaling pathway in these cells and their intimate connections with blood vessels indicate that these neurons exert direct neurovascular coupling.

Can distinctly different rapid estrogen actions share a common mechanistic step?

Contribution to Special Issue on Fast effects of steroids. This paper reviews early evidence for the existence of rapid, non-genomic effects of estrogens on neurons, and, further, proposes that these rapid effects are often synergistic with later, genomic effects. Finally, suggestions about potential molecular mechanisms underlying the rapid effects of estrogens are offered.

Reproducibility and replicability of rodent phenotyping in preclinical studies.

The scientific community is increasingly concerned with the proportion of published "discoveries" that are not replicated in subsequent studies. The field of rodent behavioral phenotyping was one of the first to raise this concern, and to relate it to other methodological issues: the complex interaction between genotype and environment; the definitions of behavioral constructs; and the use of laboratory mice and rats as model species for investigating human health and disease mechanisms. In January 2015, researchers from various disciplines gathered at Tel Aviv University to discuss these issues.

Building Bridges through Science.

Science is ideally suited to connect people from different cultures and thereby foster mutual understanding. To promote international life science collaboration, we have launched "The Science Bridge" initiative. Our current project focuses on partnership between Western and Middle Eastern neuroscience communities.

Hormone-dependent medial preoptic/lumbar spinal cord/autonomic coordination supporting male sexual behaviors.

Testosterone (T) can act directly through neural androgen receptors (AR) to facilitate male sexual behavior; however, T's metabolites also can play complicated and interesting roles in the control of mating. One metabolite, dihydrotestosterone (DHT) binds to AR with significantly greater affinity than that of T. Is that important behaviorally? Another metabolite, estradiol (E), offers a potential alternative route of facilitating male mating behavior by acting through estradiol receptors (ER).

Sex-specific gene-environment interactions underlying ASD-like behaviors.

The male bias in the incidence of autism spectrum disorders (ASDs) is one of the most notable characteristics of this group of neurodevelopmental disorders. The etiology of this sex bias is far from known, but pivotal for understanding the etiology of ASDs in general. Here we investigate whether a "three-hit" (genetic load × environmental factor × sex) theory of autism may help explain the male predominance.

Development of Electrophysiological Properties of Nucleus Gigantocellularis Neurons Correlated with Increased CNS Arousal.

Many types of data have suggested that neurons in the nucleus gigantocellularis (NGC) in the medullary reticular formation are critically important for CNS arousal and behavioral responsiveness. To extend this topic to a developmental framework, whole-cell patch-recorded characteristics of NGC neurons in brainstem slices and measures of arousal-dependent locomotion of postnatal day 3 (P3) to P6 mouse pups were measured and compared. These neuronal characteristics developed in an orderly, statistically significant monotonic manner over the course of P3-P6: (1) proportion of neurons capable of firing action potential (AP) trains, (2) AP amplitude, (3) AP threshold, (4) amplitude of inward and outward currents, (5) amplitude of negative peak currents, and (6) steady state currents (in I-V plot).

Phase-Amplitude Coupling in Spontaneous Mouse Behavior.

The level of activity of many animals including humans rises and falls with a period of ~ 24 hours. The intrinsic biological oscillator that gives rise to this circadian oscillation is driven by a molecular feedback loop with an approximately 24 hour cycle period and is influenced by the environment, most notably the light:dark cycle. In addition to the circadian oscillations, behavior of many animals is influenced by multiple oscillations occurring at faster-ultradian-time scales.

Stress and corticosteroids regulate rat hippocampal mitochondrial DNA gene expression via the glucocorticoid receptor.

Glucocorticoids (GCs) are involved in stress and circadian regulation, and produce many actions via the GC receptor (GR), which is classically understood to function as a nuclear transcription factor. However, the nuclear genome is not the only genome in eukaryotic cells. The mitochondria also contain a small circular genome, the mitochondrial DNA (mtDNA), that encodes 13 polypeptides.

Analyses of rapid estrogen actions on rat ventromedial hypothalamic neurons.

Rapid estrogen actions are widely diverse across many cell types. We conducted a series of electrophysiological studies on single rat hypothalamic neurons and found that estradiol (E2) could rapidly and independently potentiate neuronal excitation/depolarizations induced by histamine (HA) and N-Methyl-d-Aspartate (NMDA). Now, the present whole-cell patch study was designed to determine whether E2 potentiates HA and NMDA depolarizations - mediated by distinctly different types of receptors - by the same or by different mechanisms.

Rapid estrogen actions on ion channels: A survey in search for mechanisms.

A survey of nearly two hundred reports shows that rapid estrogenic actions can be detected across a range of kinds of estrogens, a range of doses, on a wide range of tissue, cell and ion channel types. Striking is the fact that preparations of estrogenic agents that do not permeate the cell membrane almost always mimic the actions of the estrogenic agents that do permeate the membrane. All kinds of estrogens, ranging from natural ones, through receptor modulators, endocrine disruptors, phytoestrogens, agonists, and antagonists to novel G-1 and STX, have been reported to be effective.