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Nature Reviews. Neuroscience Nov 2020The locus coeruleus (LC), or 'blue spot', is a small nucleus located deep in the brainstem that provides the far-reaching noradrenergic neurotransmitter system of the... (Review)
Review
The locus coeruleus (LC), or 'blue spot', is a small nucleus located deep in the brainstem that provides the far-reaching noradrenergic neurotransmitter system of the brain. This phylogenetically conserved nucleus has proved relatively intractable to full characterization, despite more than 60 years of concerted efforts by investigators. Recently, an array of powerful new neuroscience tools have provided unprecedented access to this elusive nucleus, revealing new levels of organization and function. We are currently at the threshold of major discoveries regarding how this tiny brainstem structure exerts such varied and significant influences over brain function and behaviour. All LC neurons receive inputs related to autonomic arousal, but distinct subpopulations of those neurons can encode specific cognitive processes, presumably through more specific inputs from the forebrain areas. This ability, combined with specific patterns of innervation of target areas and heterogeneity in receptor distributions, suggests that activation of the LC has more specific influences on target networks than had initially been imagined.
Topics: Animals; Cognition; Humans; Locus Coeruleus; Neural Pathways; Neuronal Plasticity; Neurons; Nucleus Accumbens
PubMed: 32943779
DOI: 10.1038/s41583-020-0360-9 -
Optics Express Apr 2022In this paper, directly following from Gage [J. Opt. Soc. Am.23, 46(1993)10.1364/JOSA.23.000046], we study the design of a particular theoretical filter for photography,...
In this paper, directly following from Gage [J. Opt. Soc. Am.23, 46(1993)10.1364/JOSA.23.000046], we study the design of a particular theoretical filter for photography, that we call the locus filter. It is built in such a way that a Wien-Planckian light (of any temperature) is spectrally mapped to another Wien-Planckian light. We provide a physical basis for designing such a filter based on the Wien approximation of Planck's law, and we prove that there exists a unique set of filters that have the desired property. While locus filtered Wien-Planckian lights are on the locus, the amount they shift depends both on the locus filter used and on the color temperature of the light. In experiments, we analyze the nature of temperature change when applying different locus filters and we show that real lights shift more or less as if they were Planckians in terms of the changes in their correlated color temperatures. We also study the quality of the filtered light in terms of distance from the Planckian locus and color rendering index.
PubMed: 35472916
DOI: 10.1364/OE.448160 -
Brain : a Journal of Neurology Mar 2022There is strong comorbidity between chronic pain and depression, although the neural circuits and mechanisms underlying this association remain unclear. By combining...
There is strong comorbidity between chronic pain and depression, although the neural circuits and mechanisms underlying this association remain unclear. By combining immunohistochemistry, tracing studies and western blotting, with the use of different DREADDS (designer receptor exclusively activated by designer drugs) and behavioural approaches in a rat model of neuropathic pain (chronic constriction injury), we explore how this comorbidity arises. To this end, we evaluated the time-dependent plasticity of noradrenergic locus coeruleus neurons relative to the site of injury: ipsilateral (LCipsi) or contralateral (LCcontra) locus coeruleus at three different time points: short (2 days), mid (7 days) and long term (30-35 days from nerve injury). Nerve injury led to sensorial hypersensitivity from the onset of injury, whereas depressive-like behaviour was only evident following long-term pain. Global chemogenetic blockade of the LCipsi system alone increased short-term pain sensitivity while the blockade of the LCipsi or LCcontra relieved pain-induced depression. The asymmetric contribution of locus coeruleus modules was also evident as neuropathy develops. Hence, chemogenetic blockade of the LCipsi→spinal cord projection, increased pain-related behaviours in the short term. However, this lateralized circuit is not universal as the bilateral chemogenetic inactivation of the locus coeruleus-rostral anterior cingulate cortex pathway or the intra-rostral anterior cingulate cortex antagonism of alpha1- and alpha2-adrenoreceptors reversed long-term pain-induced depression. Furthermore, chemogenetic locus coeruleus to spinal cord activation, mainly through LCipsi, reduced sensorial hypersensitivity irrespective of the time post-injury. Our results indicate that asymmetric activation of specific locus coeruleus modules promotes early restorative analgesia, as well as late depressive-like behaviour in chronic pain and depression comorbidity.
Topics: Animals; Comorbidity; Depression; Humans; Locus Coeruleus; Neuralgia; Neurons; Rats
PubMed: 34373893
DOI: 10.1093/brain/awab239 -
Annual Review of Vision Science Sep 2021In healthy vision, the fovea provides high acuity and serves as the locus for fixation achieved through saccadic eye movements. Bilateral loss of the foveal regions in... (Review)
Review
In healthy vision, the fovea provides high acuity and serves as the locus for fixation achieved through saccadic eye movements. Bilateral loss of the foveal regions in both eyes causes individuals to adopt an eccentric locus for fixation. This review deals with the eye movement consequences of the loss of the foveal oculomotor reference and the ability of individuals to use an eccentric fixation locus as the new oculomotor reference. Eye movements are an integral part of everyday activities, such as reading, searching for an item of interest, eye-hand coordination, navigation, or tracking an approaching car. We consider how these tasks are impacted by the need to use an eccentric locus for fixation and as a reference for eye movements, specifically saccadic and smooth pursuit eye movements.
Topics: Eye Movements; Humans; Macular Degeneration; Pursuit, Smooth; Saccades; Vision, Ocular
PubMed: 34038144
DOI: 10.1146/annurev-vision-100119-125555 -
Frontiers in Neuroscience 2022Genome-wide association studies have consistently shown that the alpha-synuclein locus is significantly associated with Parkinson's disease. The mechanism by which this... (Review)
Review
Genome-wide association studies have consistently shown that the alpha-synuclein locus is significantly associated with Parkinson's disease. The mechanism by which this locus modulates the disease pathology and etiology remains largely under-investigated. This is due to the assumption that is the only driver of the functional aspects of several single nucleotide polymorphism (SNP) risk-signals at this locus. Recent evidence has shown that the risk associated with the top GWAS-identified variant within this locus is independent of expression, calling into question the validity of assigning function to the nearest gene, . In this review, we examine additional genes and risk variants present at the locus and how they may contribute to Parkinson's disease. Using the locus as an example, we hope to demonstrate that deeper and detailed functional validations are required for high impact disease-linked variants.
PubMed: 35898413
DOI: 10.3389/fnins.2022.889802 -
Annual Review of Vision Science Sep 2023This review examines the concept of the preferred retinal locus (PRL) in patients with macular diseases. Considering monocular and binocular viewing, we () explain how... (Review)
Review
This review examines the concept of the preferred retinal locus (PRL) in patients with macular diseases. Considering monocular and binocular viewing, we () explain how to identify the PRL and discuss the pitfalls associated with its measurement, () review the current hypotheses for PRL development, () assess whether the PRL is the new reference point of the ocular motor system, and discuss () the functional and () the clinical implications of the PRL. We conclude that the current definition of the PRL is probably incomplete and should incorporate the need to evaluate the PRL in the framework of binocular viewing. We emphasize the need for more research.
Topics: Humans; Retina; Retinal Diseases
PubMed: 36944313
DOI: 10.1146/annurev-vision-111022-123909 -
Frontiers in Endocrinology 2023is a complex locus characterized by multiple transcripts and an imprinting effect. It orchestrates a variety of physiological processes via numerous signaling pathways.... (Review)
Review
is a complex locus characterized by multiple transcripts and an imprinting effect. It orchestrates a variety of physiological processes via numerous signaling pathways. Human diseases associated with the gene encompass fibrous dysplasia (FD), Albright's Hereditary Osteodystrophy (AHO), parathyroid hormone(PTH) resistance, and Progressive Osseous Heteroplasia (POH), among others. To facilitate the study of the locus and its associated diseases, researchers have developed a range of mouse models. In this review, we will systematically explore the locus, its related signaling pathways, the bone diseases associated with it, and the mouse models pertinent to these bone diseases.
Topics: Animals; Mice; Humans; GTP-Binding Protein alpha Subunits, Gs; Chromogranins; Pseudohypoparathyroidism; Bone Diseases, Metabolic; Ossification, Heterotopic
PubMed: 37920253
DOI: 10.3389/fendo.2023.1255864 -
Proceedings of the National Academy of... Nov 2021The last decade has seen significant progress identifying genetic and brain differences related to intelligence. However, there remain considerable gaps in our... (Review)
Review
The last decade has seen significant progress identifying genetic and brain differences related to intelligence. However, there remain considerable gaps in our understanding of how cognitive mechanisms that underpin intelligence map onto various brain functions. In this article, we argue that the locus coeruleus-norepinephrine system is essential for understanding the biological basis of intelligence. We review evidence suggesting that the locus coeruleus-norepinephrine system plays a central role at all levels of brain function, from metabolic processes to the organization of large-scale brain networks. We connect this evidence with our executive attention view of working-memory capacity and fluid intelligence and present analyses on baseline pupil size, an indicator of locus coeruleus activity. Using a latent variable approach, our analyses showed that a common executive attention factor predicted baseline pupil size. Additionally, the executive attention function of disengagement--not maintenance--uniquely predicted baseline pupil size. These findings suggest that the ability to control attention may be important for understanding how cognitive mechanisms of fluid intelligence map onto the locus coeruleus-norepinephrine system. We discuss how further research is needed to better understand the relationships between fluid intelligence, the locus coeruleus-norepinephrine system, and functionally organized brain networks.
Topics: Animals; Attention; Brain; Executive Function; Humans; Individuality; Intelligence; Locus Coeruleus; Memory, Short-Term; Norepinephrine; Pupil
PubMed: 34764223
DOI: 10.1073/pnas.2110630118 -
Brain : a Journal of Neurology Sep 2021Many aspects of cognition and behaviour are regulated by noradrenergic projections to the forebrain originating from the locus coeruleus, acting through alpha and beta... (Review)
Review
Many aspects of cognition and behaviour are regulated by noradrenergic projections to the forebrain originating from the locus coeruleus, acting through alpha and beta adrenoreceptors. Loss of these projections is common in neurodegenerative diseases and contributes to their cognitive and behavioural deficits. We review the evidence for a noradrenergic modulation of cognition in its contribution to Alzheimer's disease, Parkinson's disease and other cognitive disorders. We discuss the advances in human imaging and computational methods that quantify the locus coeruleus and its function in humans, and highlight the potential for new noradrenergic treatment strategies.
Topics: Cognition; Cognition Disorders; Humans; Locus Coeruleus; Norepinephrine
PubMed: 33725122
DOI: 10.1093/brain/awab111