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Bidirectional Anticipation of Future Osmotic Challenges by Vasopressin Neurons.

ABSTRACT: Ingestion of water and food are major hypo- and hyperosmotic challenges. To protect the body from osmotic stress, posterior pituitary-projecting, vasopressin-secreting neurons (VPpp neurons) counter osmotic perturbations by altering their release of vasopressin, which controls renal water excretion. Vasopressin levels begin to fall within minutes of water consumption, even prior to changes in blood osmolality. To ascertain the precise temporal dynamics by which water or food ingestion affect VPpp neuron activity, we directly recorded the spiking and calcium activity of genetically defined VPpp neurons. In states of elevated osmolality, water availability rapidly decreased VPpp neuron activity within seconds, beginning prior to water ingestion, upon presentation of water-predicting cues. In contrast, food availability following food restriction rapidly increased VPpp neuron activity within seconds, but only following feeding onset. These rapid and distinct changes in activity during drinking and feeding suggest diverse neural mechanisms underlying anticipatory regulation of VPpp neurons.

SUBMITTER: Mandelblat-Cerf Y

PROVIDER: S-EPMC5215952 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Bidirectional Anticipation of Future Osmotic Challenges by Vasopressin Neurons.

Mandelblat-Cerf Yael Y Kim Angela A Burgess Christian R CR Subramanian Siva S Tannous Bakhos A BA Lowell Bradford B BB Andermann Mark L ML

Neuron 20161215 1

Ingestion of water and food are major hypo- and hyperosmotic challenges. To protect the body from osmotic stress, posterior pituitary-projecting, vasopressin-secreting neurons (VP<sub>pp</sub> neurons) counter osmotic perturbations by altering their release of vasopressin, which controls renal water excretion. Vasopressin levels begin to fall within minutes of water consumption, even prior to changes in blood osmolality. To ascertain the precise temporal dynamics by which water or food ingestion ...[more]

PMID: 27989461

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Project description:Neurons that synthesize melanin-concentrating hormone (MCH) colocalize GABA, regulate energy homeostasis, modulate water intake, and influence anxiety, stress, and social interaction. Similarly, vasopressin and oxytocin can influence the same behaviors and states, suggesting that these neuropeptides may exert part of their effect by modulating MCH neurons. Using whole cell recording in MCH-green fluorescent protein (GFP) transgenic mouse hypothalamic brain slices, we found that both vasopressin and oxytocin evoked a substantial excitatory effect. Both peptides reversibly increased spike frequency and depolarized the membrane potential in a concentration-dependent and tetrodotoxin-resistant manner, indicating a direct effect. Substitution of lithium for extracellular sodium, Na(+)/Ca(2+) exchanger blockers KB-R7943 and SN-6, and intracellular calcium chelator BAPTA, all substantially reduced the vasopressin-mediated depolarization, suggesting activation of the Na(+)/Ca(2+) exchanger. Vasopressin reduced input resistance, and the vasopressin-mediated depolarization was attenuated by SKF-96265, suggesting a second mechanism based on opening nonselective cation channels. Neither vasopressin nor oxytocin showed substantial excitatory actions on lateral hypothalamic inhibitory neurons identified in a glutamate decarboxylase 67 (GAD67)-GFP mouse. The primary vasopressin receptor was vasopressin receptor 1a (V1aR), as suggested by the excitation by V1aR agonist [Arg(8)]vasotocin, the selective V1aR agonist [Phe(2)]OVT and by the presence of V1aR mRNA in MCH cells, but not in other nearby GABA cells, as detected with single-cell RT-PCR. Oxytocin receptor mRNA was also detected in MCH neurons. Together, these data suggest that vasopressin or oxytocin exert a minimal effect on most GABA neurons in the lateral hypothalamus but exert a robust excitatory effect on presumptive GABA cells that contain MCH. Thus, some of the central actions of vasopressin and oxytocin may be mediated through MCH cells.

Project description:In 2011, one of the authors (DJB) published a report of nine experiments in the Journal of Personality and Social Psychology purporting to demonstrate that an individual's cognitive and affective responses can be influenced by randomly selected stimulus events that do not occur until after his or her responses have already been made and recorded, a generalized variant of the phenomenon traditionally denoted by the term precognition. To encourage replications, all materials needed to conduct them were made available on request. We here report a meta-analysis of 90 experiments from 33 laboratories in 14 countries which yielded an overall effect greater than 6 sigma, z = 6.40, p = 1.2 × 10 (-10 ) with an effect size (Hedges' g) of 0.09. A Bayesian analysis yielded a Bayes Factor of 5.1 × 10 (9), greatly exceeding the criterion value of 100 for "decisive evidence" in support of the experimental hypothesis. When DJB's original experiments are excluded, the combined effect size for replications by independent investigators is 0.06, z = 4.16, p = 1.1 × 10 (-5), and the BF value is 3,853, again exceeding the criterion for "decisive evidence." The number of potentially unretrieved experiments required to reduce the overall effect size of the complete database to a trivial value of 0.01 is 544, and seven of eight additional statistical tests support the conclusion that the database is not significantly compromised by either selection bias or by intense " p-hacking"-the selective suppression of findings or analyses that failed to yield statistical significance. P-curve analysis, a recently introduced statistical technique, estimates the true effect size of the experiments to be 0.20 for the complete database and 0.24 for the independent replications, virtually identical to the effect size of DJB's original experiments (0.22) and the closely related "presentiment" experiments (0.21). We discuss the controversial status of precognition and other anomalous effects collectively known as psi.

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Bidirectional Anticipation of Future Osmotic Challenges by Vasopressin Neurons.

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Bidirectional Anticipation of Future Osmotic Challenges by Vasopressin Neurons.

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