A unified survival theory of the functioning of the hypocretinergic system

2013 ◽  
Vol 115 (7) ◽  
pp. 954-971 ◽  
Author(s):  
Michael H. Chase
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Food Consumption ◽  
Lateral Hypothalamus ◽  
Basic Science ◽  
A Priori ◽  
Behavioral Data ◽  
Control Survival

This article advances the theory that the hypocretinergic (orexinergic) system initiates, coordinates, and maintains survival behaviors and survival-related processes (i.e., the Unified Survival Theory of the Functioning of the Hypocretinergic System or “Unified Hypocretinergic Survival Theory”). A priori presumptive support for the Unified Hypocretinergic Survival Theory emanates from the fact that neurons that contain hypocretin are located in the key executive central nervous system (CNS) site, the lateral hypothalamus, that for decades has been well-documented to govern core survival behaviors such as fight, flight, and food consumption. In addition, the hypocretinergic system exhibits the requisite morphological and electrophysiological capabilities to control survival behaviors and related processes. Complementary behavioral data demonstrate that all facets of “survival” are coordinated by the hypocretinergic system and that hypocretinergic directives are not promulgated except during survival behaviors. Importantly, it has been shown that survival behaviors are selectively impacted when the hypocretinergic system is impaired or rendered nonfunctional, whereas other behaviors are relatively unaffected. The Unified Hypocretinergic Survival Theory resolves the disparate, perplexing, and often paradoxical-appearing results of previous studies; it also provides a foundation for future hypothesis-driven basic science and clinical explorations of the hypocretinergic system.

scholarly journals Manifold reaching paradigm: how do we handle target redundancy?

2011 ◽  
Vol 106 (4) ◽  
pp. 2086-2102 ◽  
Author(s):  
Bastien Berret ◽  
Enrico Chiovetto ◽  
Francesco Nori ◽  
Thierry Pozzo
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Degrees Of Freedom ◽  
A Priori ◽  
Movement Planning ◽  
Optimal Feedback Control ◽  
Target Redundancy ◽  
The Central Nervous System ◽  
Point To Point ◽  
Muscle Activations

How the central nervous system coordinates the many intrinsic degrees of freedom of the musculoskeletal system is a recurrent question in motor control. Numerous studies addressed it by considering redundant reaching tasks such as point-to-point arm movements, for which many joint trajectories and muscle activations are usually compatible with a single goal. There exists, however, a different, extrinsic kind of redundancy that is target redundancy. Many times, indeed, the final point to reach is neither specified nor unique. In this study, we aim to understand how the central nervous system tackles such an extrinsic redundancy by considering a reaching-to-a-manifold paradigm, more specifically an arm pointing to a long vertical bar. In this case, the endpoint is not defined a priori and, therefore, subjects are free to choose any point on the bar to successfully achieve the task. We investigated the strategies used by subjects to handle this presented choice. Our results indicate both intersubject and intertrial consistency with respect to the freedom provided by the task. However, the subjects' behavior is found to be more variable than during classical point-to-point reaches. Interestingly, the average arm trajectories to the bar and the structure of intertrial endpoint variations could be explained via stochastic optimal control with an energy/smoothness expected cost and signal-dependent motor noise. We conclude that target redundancy is first overcome during movement planning and then exploited during movement execution, in agreement with stochastic optimal feedback control principles, which illustrates how the complementary problems of goal and movement selection may be resolved at once.

scholarly journals Analysis of novel domain-specific mutations in the zebrafish ndr2/cyclops gene generated using CRISPR-Cas9 RNPs

2018 ◽  
Author(s):  
Ashley N. Turner ◽  
Reagan S. Andersen ◽  
Ivy E. Bookout ◽  
Lauren N. Brashear ◽  
James C. Davis ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Transforming Growth Factor ◽  
A Priori ◽  
Chemical Mutagenesis ◽  
Sequence Information ◽  
Small Indels ◽  
Domain Specific

AbstractNodal-related protein (ndr2) is a member of the transforming growth factor type β superfamily of factors and is required for ventral midline patterning of the embryonic central nervous system in zebrafish. In humans, mutations in the gene encoding nodal cause holoprosencephaly and heterotaxy. Mutations in the ndr2 gene in the zebrafish (Danio rerio) lead to similar phenotypes, including loss of the medial floor plate, severe deficits in ventral forebrain development, and cyclopia. Alleles of the ndr2 gene have been useful in studying patterning of ventral structures of the central nervous system. Fifteen different ndr2 alleles have been reported in zebrafish, of which eight were generated using chemical mutagenesis, four were radiation-induced, and the remaining alleles were obtained via random insertion, gene targeting (TALEN), or unknown methods. Therefore, most mutation sites were random and could not be predicted a priori. Using the CRISPR-Cas9 system from Streptococcus pyogenes, we targeted distinct regions in all three exons of zebrafish ndr2 and observed cyclopia in the injected (G0) embryos. We show that the use of sgRNA-Cas9 ribonucleoprotein (RNP) complexes can cause penetrant cyclopic phenotypes in injected (G0) embryos. Targeted PCR amplicon analysis using Sanger sequencing showed that most of the alleles had small indels resulting in frameshifts. The sequence information correlates with the loss of ndr2 activity. In this study, we validate multiple CRISPR targets using an in vitro nuclease assay and in vivo analysis using embryos. We describe one specific mutant allele resulting in loss of conserved terminal cysteine-coding sequences. This study is another demonstration of the utility of the CRISPR-Cas9 system in generating domain- specific mutations and provides further insights into the structure-function of the ndr2 gene.

scholarly journals The orexins/hypocretins: hypothalamic peptides linked to sleep and appetite

2002 ◽  
Vol 32 (6) ◽  
pp. 955-958 ◽  
Author(s):  
SHAHRAD TAHERI ◽  
SEPEHR HAFIZI
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Sleep Disorder ◽  
Psychiatric Disorders ◽  
Lateral Hypothalamus ◽  
Scientific Knowledge ◽  
State Of The Art ◽  
Molecular Techniques ◽  
Medical Community ◽  
The Central Nervous System

The orexins/hypocretins are novel neuropeptides synthesized by neurons whose cell bodies are located in the lateral hypothalamus. Although these neurons are few in number, they send projections widely throughout the central nervous system (Kilduff & Peyron, 2000). There has been great excitement about the orexins/hypocretins from both the scientific and medical community. These peptides are remarkable in that they were discovered using state-of-the-art molecular techniques before their physiological actions were studied. Furthermore, there has been an exponential progress in our scientific knowledge of these peptides culminating in the orexins/hypocretins being linked to the sleep disorder, narcolepsy. With the importance of the orexins/hypocretins in sleep and arousal being increasingly recognized, it is likely that these peptides are altered by or contribute to several medical and psychiatric disorders.

Brain-Immune Interactions in Neuropsychiatry: Highlights of the Basic Science and Relevance to Pathogenic Factors and Epiphenomena

CNS Spectrums ◽  
2001 ◽  
Vol 6 (5) ◽  
pp. 383-391 ◽  
Author(s):  
John M. Petitto ◽  
Martin J. Repetto ◽  
David A. Hartemink
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Basic Science ◽  
Clinical Implications ◽  
Potential Treatment ◽  
Considerable Research ◽  
Pathogenic Factors ◽  
Treatment Considerations ◽  
Immunological Changes ◽  
Basic Studies

AbstractUnraveling the significant complexity of brain-immune interactions could provide essential new insights and potential treatment considerations for the clinical neurosciences. Despite considerable research relating immunological changes to major neuropsychiatric disorders, it has been difficult to establish that immunological processes are involved in the development of central nervous system pathology associated with these disorders. This brief article highlights some of the landmark basic studies and seeks to convey essential principles guiding research in brain-immune interactions. Research in this area often incorporates several disciplines, ranging from psychology and neuroscience to immunology and molecular genetics. The clinical implications of this area of research are discussed, with emphasis on the challenge of disentangling pathogenic factors and valid markers of disease from epiphenomena.

scholarly journals Central Nervous System and Peripheral Hormone Responses to a Meal in Children

2018 ◽  
Vol 104 (5) ◽  
pp. 1471-1483 ◽  
Author(s):  
Christian L Roth ◽  
Susan J Melhorn ◽  
Clinton T Elfers ◽  
Kelley Scholz ◽  
Mary Rosalynn B De Leon ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
A Priori ◽  
Puget Sound ◽  
Brain Activation ◽  
Healthy Weight ◽  
Hormone Response ◽  
Food Cues ◽  
Gut Hormone ◽  
High Calorie

Abstract Context Behavioral studies suggest that responses to food consumption are altered in children with obesity (OB). Objective To test central nervous system and peripheral hormone response by functional MRI and satiety-regulating hormone levels before and after a meal. Design and Setting Cross-sectional study comparing children with OB and children of healthy weight (HW) recruited from across the Puget Sound region of Washington. Participants Children (9 to 11 years old; OB, n = 54; HW, n = 22), matched for age and sex. Intervention and Outcome Measures Neural activation to images of high- and low-calorie food and objects was evaluated across a set of a priori appetite-processing regions that included the ventral and dorsal striatum, amygdala, substantia nigra/ventral tegmental area, insula, and medial orbitofrontal cortex. Premeal and postmeal hormones (insulin, peptide YY, glucagon-like peptide-1, active ghrelin) were measured. Results In response to a meal, average brain activation by high-calorie food cues vs objects in a priori regions was reduced after meals in children of HW (Z = −3.5, P < 0.0001), but not in children with OB (z = 0.28, P = 0.78) despite appropriate meal responses by gut hormones. Although premeal average brain activation by high-calorie food cues was lower in children with OB vs children of HW, postmeal activation was higher in children with OB (Z = −2.1, P = 0.04 and Z = 2.3, P = 0.02, respectively). An attenuated central response to a meal was associated with greater degree of insulin resistance. Conclusions Our data suggest that children with OB exhibit an attenuated central, as opposed to gut hormone, response to a meal, which may predispose them to overconsumption of food or difficulty with weight loss.

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