The locus ceruleus norepinephrine system: Functional organization and potential clinical significance

ABSTRACTEnvironmental stimuli and drugs affect the norepinephrine (NE) system and may be linked to the manifestation and treatment of anxiety and affective disorders. The activity of locus ceruleus NE neurons in the brainstem can alter the function offorebrain structures associated with several psychiatric disorders. In particular, NE neurons send and receive projections from sensory afferents, limbic areas, and cortical areas implicated in higher-order brain malfunctions and the symptomatology of anxiety and affective disorders. In turn, anxiolytic and antidepressant drugs are able to offset perturbations of NE activity and forebrain structures with a time course congruent with their therapeutic action. All antide-pressants, even the agents selective for other biogenic amines or peptides, act on the NE system. In the present review, the effects of antidepressants on NE neurons are summarized and applied to the treatment of neuropsychiatric disorders, with emphasis placed on mechanisms of action.

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Presynaptic Inhibition of Diverse Afferents to the Locus Ceruleus by -Opiate Receptors: A Novel Mechanism for Regulating the Central Norepinephrine System

Journal of Neuroscience ◽

10.1523/jneurosci.0390-08.2008 ◽

2008 ◽

Vol 28 (25) ◽

pp. 6516-6525 ◽

Cited By ~ 63

Author(s):

A. Kreibich ◽

B. A. S. Reyes ◽

A. L. Curtis ◽

L. Ecke ◽

C. Chavkin ◽

...

Keyword(s):

Presynaptic Inhibition ◽

Opiate Receptors ◽

Locus Ceruleus ◽

Norepinephrine System

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Faculty Opinions recommendation of Presynaptic inhibition of diverse afferents to the locus ceruleus by kappa-opiate receptors: a novel mechanism for regulating the central norepinephrine system.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1115737.571817 ◽

2008 ◽

Author(s):

Yvette Taché

Keyword(s):

Presynaptic Inhibition ◽

Opiate Receptors ◽

Locus Ceruleus ◽

Norepinephrine System

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The locus coeruleus-norepinephrine system and fluid intelligence

10.31234/osf.io/eg3vw ◽

2020 ◽

Cited By ~ 1

Author(s):

Jason S. Tsukahara ◽

Randall W Engle

Keyword(s):

Working Memory ◽

Locus Coeruleus ◽

Resting State ◽

Pupil Size ◽

Fluid Intelligence ◽

Functional Organization ◽

Working Memory Capacity ◽

Memory Capacity ◽

Executive Attention ◽

Norepinephrine System

The locus coeruleus-norepinephrine system is uniquely situated to influence a wide-array of brain and cellular processes at all levels of brain functions. We review the literature on the locus-coeruleus-norepinephrine system in relation to fluid intelligence within the context of our executive attention theory. We discuss evidence suggesting the locus coeruleus-norepinephrine system plays an important role in the functional organization of the resting-state brain and that this can explain our finding from Tsukahara et al. (2016) that higher fluid intelligence and working memory capacity is associated with a larger baseline pupil size. However, other researchers have not been able to replicate our 2016 finding – though they only measured working memory capacity and not fluid intelligence. In a reanalysis of Tsukahara et al. (2016) we show that reduced variability on baseline pupil size will result in a higher probability of obtaining smaller and non-significant correlations with working memory capacity. In two large-scale studies, we demonstrated that reduced variability in baseline pupil size values down to minimal physiological limits can be obtained if the monitor is too bright. Additionally, fluid intelligence and working memory capacity do correlate with baseline pupil size except in the brightest lighting conditions. We also investigated the relationship of higher-order cognition to baseline pupil size within the context of our executive attention theory. Therefore, we conclude that fluid intelligence does correlate with baseline pupil size and that this is related to the functional organization of the resting-state brain through the locus coeruleus-norepinephrine system.

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Organization of transcription and pre-mRNA splicing within the mammalian cell nucleus

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010014021x ◽

1995 ◽

Vol 53 ◽

pp. 768-769

Author(s):

D.L. Spector ◽

S. Huang ◽

S. Kaurin

Keyword(s):

Rna Polymerase Ii ◽

Cell Nucleus ◽

Functional Organization ◽

Mrna Splicing ◽

Splicing Factors ◽

Interchromatin Granule Clusters ◽

Interchromatin Granule ◽

Nuclear Regions ◽

Relationship Of ◽

Perichromatin Fibrils

We have been interested in the organization of RNA polymerase II transcription and pre-mRNA splicing within the cell nucleus. Several models have been proposed for the functional organization of RNA within the eukaryotic nucleus and for the relationship of this organization to the distribution of pre-mRNA splicing factors. One model suggests that RNAs which must be spliced are capable of recruiting splicing factors to the sites of transcription from storage and/or reassembly sites. When one examines the organization of splicing factors in the nucleus in comparison to the sites of chromatin it is clear that splicing factors are not localized in coincidence with heterochromatin (Fig. 1). Instead, they are distributed in a speckled pattern which is composed of both perichromatin fibrils and interchromatin granule clusters. The perichromatin fibrils are distributed on the periphery of heterochromatin and on the periphery of interchromatin granule clusters as well as being diffusely distributed throughout the nucleoplasm. These nuclear regions have been previously shown to represent initial sites of incorporation of 3H-uridine.

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Immunolocalization of nuclear antigens in cryofixed cells which have been prepared by molecular distillation drying or freeze-substitution

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100162053 ◽

1990 ◽

Vol 48 (3) ◽

pp. 898-899

Author(s):

David L. Spector ◽

Robert J. Derby

Keyword(s):

Cell Nucleus ◽

Molecular Distillation ◽

Functional Organization ◽

Freeze Substitution ◽

3 Dimensional ◽

Small Nuclear Ribonucleoprotein ◽

Nuclear Antigens ◽

Dimensional Reconstruction ◽

Nuclear Regions ◽

Immunoperoxidase Labeling

Studies in our laboratory are involved in evaluating the structural and functional organization of the mammalian cell nucleus. Since several major classes (U1, U2, U4/U6, U5) of small nuclear ribonucleoprotein particles (snRNPs) play a crucial role in the processing of pre-mRNA molecules, we have been interested in the localization of these particles within the cell nucleus. Using pre-embedding immunoperoxidase labeling combined with 3-dimensional reconstruction, we have recently shown that nuclear regions enriched in snRNPs form a reticular network within the nucleoplasm which extends between the nucleolar surface and the nuclear envelope. In the present study we were inte rested in extending these nuclear localizations using cell preparation techniques which avoid slow penetration of fixatives, chemical crosslinking of potential antigens and solvent extraction. CHOC 400 cells were cryofixed using a CF 100 ultra rapid cooling device (LifeCell Corp.). After cryofixation cells were molecular distillation dried, vapor osmicated, in filtra ted in 100% Spurr resin in vacuo and polymerized in molds a t 60°C. Using this procedure we were able to evaluate the distribution of snRNPs in resin embedded cells which had not been chemically fixed, incubated in cryoprotectants or extracted with solvents.

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