scholarly journals Learning naturalistic temporal structure in the posterior medial network

2017 ◽  
Author(s):  
Mariam Aly ◽  
Janice Chen ◽  
Nicholas B. Turk-Browne ◽  
Uri Hasson
Keyword(s):  
De Novo ◽  
Temporal Structure ◽  
Temporal Integration ◽  
Functional Coupling ◽  
Relative Role ◽  
Dynamics And Function ◽  
And Function ◽  
The Brain ◽  
Event Schemas

AbstractThe posterior medial network is at the apex of a temporal integration hierarchy in the brain, integrating information over many seconds of viewing intact, but not scrambled, movies. This has been interpreted as an effect of temporal structure. Such structure in movies depends on pre-existing event schemas, but temporal structure can also arise de novo from learning. Here we examined the relative role of schema-consistent temporal structure and arbitrary but consistent temporal structure on the human posterior medial network. We tested whether, with repeated viewing, the network becomes engaged by scrambled movies with temporal structure. Replicating prior studies, posterior medial regions were immediately locked to stimulus structure upon exposure to intact but not scrambled movies. However, for temporally structured scrambled movies, functional coupling within the network increased across stimulus repetitions, rising to the level of intact movies. Thus, temporal structure is a key determinant of network dynamics and function.

scholarly journals Learning Naturalistic Temporal Structure in the Posterior Medial Network

2018 ◽  
Vol 30 (9) ◽  
pp. 1345-1365 ◽  
Author(s):  
Mariam Aly ◽  
Janice Chen ◽  
Nicholas B. Turk-Browne ◽  
Uri Hasson
Keyword(s):  
De Novo ◽  
Temporal Structure ◽  
Temporal Integration ◽  
Functional Coupling ◽  
Relative Role ◽  
Dynamics And Function ◽  
And Function ◽  
The Brain ◽  
Event Schemas

The posterior medial network is at the apex of a temporal integration hierarchy in the brain, integrating information over many seconds of viewing intact, but not scrambled, movies. This has been interpreted as an effect of temporal structure. Such structure in movies depends on preexisting event schemas, but temporal structure can also arise de novo from learning. Here, we examined the relative role of schema-consistent temporal structure and arbitrary but consistent temporal structure on the human posterior medial network. We tested whether, with repeated viewing, the network becomes engaged by scrambled movies with temporal structure. Replicating prior studies, activity in posterior medial regions was immediately locked to stimulus structure upon exposure to intact, but not scrambled, movies. However, for temporally structured scrambled movies, functional coupling within the network increased across stimulus repetitions, rising to the level of intact movies. Thus, temporal structure is a key determinant of network dynamics and function in the posterior medial network.

scholarly journals The Role of the Proteasome in Platelet Function

2021 ◽  
Vol 22 (8) ◽  
pp. 3999
Author(s):  
Abed El-Hakim El-Kadiry ◽  
Yahye Merhi
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
De Novo ◽  
Functional Coupling ◽  
Platelet Activity ◽  
Vascular Integrity ◽  
Primary Hemostasis ◽  
Limited Protein ◽  
And Function

Platelets are megakaryocyte-derived acellular fragments prepped to maintain primary hemostasis and thrombosis by preserving vascular integrity. Although they lack nuclei, platelets harbor functional genomic mediators that bolster platelet activity in a signal-specific manner by performing limited de novo protein synthesis. Furthermore, despite their limited protein synthesis, platelets are equipped with multiple protein degradation mechanisms, such as the proteasome. In nucleated cells, the functions of the proteasome are well established and primarily include proteostasis among a myriad of other signaling processes. However, the role of proteasome-mediated protein degradation in platelets remains elusive. In this review article, we recapitulate the developing literature on the functions of the proteasome in platelets, discussing its emerging regulatory role in platelet viability and function and highlighting how its functional coupling with the transcription factor NF-κB constitutes a novel potential therapeutic target in atherothrombotic diseases.

scholarly journals Synthesis and Function of Hypothalamic Neuroprogesterone in Reproduction

Endocrinology ◽  
2008 ◽  
Vol 149 (6) ◽  
pp. 2739-2742 ◽  
Author(s):  
Paul Micevych ◽  
Kevin Sinchak
Keyword(s):  
Metabotropic Glutamate Receptor ◽  
De Novo ◽  
Progesterone Receptors ◽  
Calcium Stores ◽  
Steroid Synthesis ◽  
Metabotropic Glutamate ◽  
And Function ◽  
The Brain ◽  
Peripheral Origin

The physiology and regulation of steroid synthesis in the brain have emerged as important for understanding brain function. Neurosteroids, those steroids synthesized de novo in nervous tissue, have been associated with numerous central nervous system functions, including myelination, mental retardation, and epilepsy. Central regulation of reproduction was thought to depend on steroids of peripheral origin. Only recently has the role of neurosteroids in reproduction been appreciated. This minireview describes our work trying to understand how circulating estradiol modulates the synthesis of neuroprogesterone. The synthesis of neuroprogesterone occurs primarily in astrocytes, and requires the interaction of membrane-associated estrogen receptor with metabotropic glutamate receptor and the release of intracellular calcium stores. The newly synthesized neuroprogesterone acts on estradiol-induced progesterone receptors in nearby neurons to initiate the LH surge.

The role of GABAA receptor biogenesis, structure and function in epilepsy

2006 ◽  
Vol 34 (5) ◽  
pp. 863-867 ◽  
Author(s):  
S. Mizielinska ◽  
S. Greenwood ◽  
C.N. Connolly
Keyword(s):  
Gabaa Receptor ◽  
Structure And Function ◽  
Inhibitory Synapses ◽  
Normal Brain ◽  
Synaptic Targeting ◽  
Acid Type ◽  
Normal Brain Function ◽  
And Function ◽  
The Brain

Maintaining the correct balance in neuronal activation is of paramount importance to normal brain function. Imbalances due to changes in excitation or inhibition can lead to a variety of disorders ranging from the clinically extreme (e.g. epilepsy) to the more subtle (e.g. anxiety). In the brain, the most common inhibitory synapses are regulated by GABAA (γ-aminobutyric acid type A) receptors, a role commensurate with their importance as therapeutic targets. Remarkably, we still know relatively little about GABAA receptor biogenesis. Receptors are constructed as pentameric ion channels, with α and β subunits being the minimal requirement, and the incorporation of a γ subunit being necessary for benzodiazepine modulation and synaptic targeting. Insights have been provided by the discovery of several specific assembly signals within different GABAA receptor subunits. Moreover, a number of recent studies on GABAA receptor mutations associated with epilepsy have further enhanced our understanding of GABAA receptor biogenesis, structure and function.

scholarly journals Sex Differences and the Influence of Sex Hormones on Cognition through Adulthood and the Aging Process

2018 ◽  
Vol 8 (9) ◽  
pp. 163 ◽  
Author(s):  
Caroline Gurvich ◽  
Kate Hoy ◽  
Natalie Thomas ◽  
Jayashri Kulkarni
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Differences ◽  
Cognitive Functioning ◽  
Sex Hormones ◽  
Reproductive Function ◽  
Health And Disease ◽  
And Function ◽  
The Brain

Hormones of the hypothalamic-pituitary-gonadal (HPG) axis that regulate reproductive function have multiple effects on the development, maintenance and function of the brain. Sex differences in cognitive functioning have been reported in both health and disease, which may be partly attributed to sex hormones. The aim of the current paper was to provide a theoretical review of how sex hormones influence cognitive functioning across the lifespan as well as provide an overview of the literature on sex differences and the role of sex hormones in cognitive decline, specifically in relation to Alzheimer’s disease (AD). A summary of current hormone and sex-based interventions for enhancing cognitive functioning and/or reducing the risk of Alzheimer’s disease is also provided.

Brain structure and function related to headache: Brainstem structure and function in headache

Cephalalgia ◽  
2018 ◽  
Vol 39 (13) ◽  
pp. 1635-1660 ◽  
Author(s):  
Marta Vila-Pueyo ◽  
Jan Hoffmann ◽  
Marcela Romero-Reyes ◽  
Simon Akerman
Keyword(s):  
Primary Headache ◽  
Structure And Function ◽  
Affective Processing ◽  
Primary Headaches ◽  
Headache Disorders ◽  
Primary Headache Disorders ◽  
Brain Structure And Function ◽  
And Function ◽  
The Brain

Objective To review and discuss the literature relevant to the role of brainstem structure and function in headache. Background Primary headache disorders, such as migraine and cluster headache, are considered disorders of the brain. As well as head-related pain, these headache disorders are also associated with other neurological symptoms, such as those related to sensory, homeostatic, autonomic, cognitive and affective processing that can all occur before, during or even after headache has ceased. Many imaging studies demonstrate activation in brainstem areas that appear specifically associated with headache disorders, especially migraine, which may be related to the mechanisms of many of these symptoms. This is further supported by preclinical studies, which demonstrate that modulation of specific brainstem nuclei alters sensory processing relevant to these symptoms, including headache, cranial autonomic responses and homeostatic mechanisms. Review focus This review will specifically focus on the role of brainstem structures relevant to primary headaches, including medullary, pontine, and midbrain, and describe their functional role and how they relate to mechanisms of primary headaches, especially migraine.

scholarly journals The Role of Adrenoceptors in the Retina

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2594
Author(s):  
Yue Ruan ◽  
Tobias Böhmer ◽  
Subao Jiang ◽  
Adrian Gericke
Keyword(s):  
Visual Information ◽  
Vision Loss ◽  
Retinal Diseases ◽  
System A ◽  
The Central Nervous System ◽  
The Individual ◽  
And Function ◽  
The Brain

The retina is a part of the central nervous system, a thin multilayer with neuronal lamination, responsible for detecting, preprocessing, and sending visual information to the brain. Many retinal diseases are characterized by hemodynamic perturbations and neurodegeneration leading to vision loss and reduced quality of life. Since catecholamines and respective bindings sites have been characterized in the retina, we systematically reviewed the literature with regard to retinal expression, distribution and function of alpha1 (α1)-, alpha2 (α2)-, and beta (β)-adrenoceptors (ARs). Moreover, we discuss the role of the individual adrenoceptors as targets for the treatment of retinal diseases.

scholarly journals A sart1 Zebrafish Mutant Results in Developmental Defects in the Central Nervous System

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2340
Author(s):  
Hannah E. Henson ◽  
Michael R. Taylor
Keyword(s):  
Central Nervous System ◽  
Cell Death ◽  
Nervous System ◽  
Developmental Defects ◽  
Whole Exome ◽  
The Central Nervous System ◽  
And Function ◽  
Upregulated Genes ◽  
The Brain

The spliceosome consists of accessory proteins and small nuclear ribonucleoproteins (snRNPs) that remove introns from RNA. As splicing defects are associated with degenerative conditions, a better understanding of spliceosome formation and function is essential. We provide insight into the role of a spliceosome protein U4/U6.U5 tri-snRNP-associated protein 1, or Squamous cell carcinoma antigen recognized by T-cells (Sart1). Sart1 recruits the U4.U6/U5 tri-snRNP complex to nuclear RNA. The complex then associates with U1 and U2 snRNPs to form the spliceosome. A forward genetic screen identifying defects in choroid plexus development and whole-exome sequencing (WES) identified a point mutation in exon 12 of sart1 in Danio rerio (zebrafish). This mutation caused an up-regulation of sart1. Using RNA-Seq analysis, we identified additional upregulated genes, including those involved in apoptosis. We also observed increased activated caspase 3 in the brain and eye and down-regulation of vision-related genes. Although splicing occurs in numerous cells types, sart1 expression in zebrafish was restricted to the brain. By identifying sart1 expression in the brain and cell death within the central nervous system (CNS), we provide additional insights into the role of sart1 in specific tissues. We also characterized sart1’s involvement in cell death and vision-related pathways.

scholarly journals P-glycoprotein (ABCB1) and Oxidative Stress: Focus on Alzheimer’s Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Giulia Sita ◽  
Patrizia Hrelia ◽  
Andrea Tarozzi ◽  
Fabiana Morroni
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Drug ◽  
Amyloid A ◽  
P Glycoprotein ◽  
And Function ◽  
The Brain ◽  
Brain Homeostasis

ATP-binding cassette (ABC) transporters, in particular P-glycoprotein (encoded by ABCB1), are important and selective elements of the blood-brain barrier (BBB), and they actively contribute to brain homeostasis. Changes in ABCB1 expression and/or function at the BBB may not only alter the expression and function of other molecules at the BBB but also affect brain environment. Over the last decade, a number of reports have shown that ABCB1 actively mediates the transport of beta amyloid (Aβ) peptide. This finding has opened up an entirely new line of research in the field of Alzheimer’s disease (AD). Indeed, despite intense research efforts, AD remains an unsolved pathology and effective therapies are still unavailable. Here, we review the crucial role of ABCB1 in the Aβtransport and how oxidative stress may interfere with this process. A detailed understanding of ABCB1 regulation can provide the basis for improved neuroprotection in AD and also enhanced therapeutic drug delivery to the brain.

scholarly journals Heterozygous variants in KCNC2 cause a broad spectrum of epilepsy phenotypes associated with characteristic functional alterations

2021 ◽  
Author(s):  
Niklas Schwarz ◽  
Simone Seiffert ◽  
Manuela Pendziwiat ◽  
Annika Rademacher ◽  
Tobias Bruenger ◽  
...  
Keyword(s):  
Functional Analysis ◽  
De Novo ◽  
Critical Role ◽  
Specific Response ◽  
Loss Of Function ◽  
Causative Gene ◽  
Characteristic Functional ◽  
Research Collaborations ◽  
The Brain

Background KCNC2 encodes a member of the shaw-related voltage-gated potassium channel family (KV3.2), which are important for sustained high-frequency firing and optimized energy efficiency of action potentials in the brain. Methods Individuals with KCNC2 variants detected by exome sequencing were selected for clinical, further genetic and functional analysis. The cases were referred through clinical and research collaborations in our study. Four de novo variants were examined electrophysiologically in Xenopus laevis oocytes. Results We identified novel KCNC2 variants in 27 patients with various forms of epilepsy. Functional analysis demonstrated gain-of-function in severe and loss-of-function in milder phenotypes as the underlying pathomechanisms with specific response to valproic acid. Conclusion These findings implicate KCNC2 as a novel causative gene for epilepsy emphasizing the critical role of KV3.2 in the regulation of brain excitability with an interesting genotype-phenotype correlation and a potential concept for precision medicine.

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