Article
Behavioral Sciences
F. Krohn, E. Lancini, M. Ludwig, M. Leiman, G. Guruprasath, L. Haag, J. Panczyszyn, E. Duezel, D. Haemmerer, M. Betts
Summary: The locus coeruleus (LC), a small structure in the brainstem, is the main source of noradrenaline (NA) in the brain. It modulates cognition, autonomic functions, and the brain's immune response. Degeneration of the LC may contribute to the pathogenesis of Alzheimer's and Parkinson's disease. Understanding early LC degeneration could provide insights into the mechanisms of these neurodegenerative diseases.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2023)
Review
Clinical Neurology
Negin Holland, Trevor W. Robbins, James B. Rowe
Summary: This review highlights the important role of noradrenergic projections from the locus coeruleus in regulating cognition and behavior, as well as their loss in neurodegenerative diseases. Advances in human imaging and computational methods for quantifying the locus coeruleus and potential new noradrenergic treatment strategies are also discussed.
Article
Multidisciplinary Sciences
Donovan K. Galvez-Marquez, Mildred Salgado-Menez, Perla Moreno-Castilla, Luis Rodriguez-Duran, Martha L. Escobar, Fatuel Tecuapetla, Federico Bermudez-Rattoni
Summary: This study found that decreasing catecholamine release from the locus coeruleus terminals in the hippocampus can impact the updating of spatial contextual memory. Photoinhibtion of these terminals impaired the consolidation of object location memory and led to a decrease in both dopamine and noradrenaline levels. This data suggests that dopamine plays a role in the mechanisms of spatial contextual memory updating.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Endocrinology & Metabolism
Nils Korte, Greg James, Haoming You, Chanawee Hirunpattarasilp, Isabel Christie, Huma Sethi, David Attwell
Summary: Noradrenaline released from Locus coeruleus axons induces vascular contraction in arteriolar smooth muscle and capillary pericytes. This contraction is mediated via alpha(2) adrenergic receptors and does not elevate intracellular calcium levels. Activation of alpha(2) adrenergic receptors can stimulate pericyte contraction while blocking them reduces noradrenaline-induced pericyte contraction. These findings suggest that alpha(2) adrenergic receptors play a role in regulating cerebral blood flow and could be targeted for therapeutic purposes.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2023)
Review
Geriatrics & Gerontology
Niels Hansen, Alina Isabel Rediske
Summary: Studies suggest that in delirium states, excessive or low arousal directly affects the release and transmission of noradrenaline, leading to deficits in cognitive function and attention.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Neurosciences
Lars Emil Larsen, Sielke Caestecker, Latoya Stevens, Pieter van Mierlo, Evelien Carrette, Paul Boon, Kristl Vonck, Robrecht Raedt
Summary: This study assessed the activity of locus coeruleus neurons and changes in noradrenergic transmission during acute hippocampal seizures. The results showed both inhibition and excitation of LC neurons during seizures, but a consistent release of noradrenaline was observed.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Neurosciences
Shigeki Hirano, Atsuhiko Sugiyama, Kimihito Arai
Summary: In 1967, the presence of monoamine-containing fibers in the rat cerebellum was demonstrated, providing clinical relevance of the noradrenergic system to the cerebellum. Cerebellar dysfunction and the noradrenergic system may be implicated in various diseases and symptoms, such as tremor in Parkinson's disease, motor learning in spinocerebellar ataxias, and cognitive and emotional symptoms in Alzheimer's disease and attention-deficit/hyperactivity disorder. While recent advances in neuroimaging have helped evaluate the noradrenergic system, more research is needed to fully understand the pathophysiological relationship between the cerebellum and the noradrenergic system and its clinical implications.
Article
Neurosciences
Roman Dvorkin, Stephen D. Shea
Summary: The noradrenergic locus coeruleus (LC) plays an important role in social behavior by coordinating phasic activity with specific social events and communicating tonic activity throughout the brain.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Clinical Neurology
Claire O'Callaghan, Frank H. Hezemans, Rong Ye, Catarina Rua, P. Simon Jones, Alexander G. Murley, Negin Holland, Ralf Regenthal, Kamen A. Tsvetanov, Noham Wolpe, Roger A. Barker, Caroline H. Williams-Gray, Trevor W. Robbins, Luca Passamonti, James B. Rowe
Summary: Cognitive decline is common in Parkinson's disease and often unresponsive to dopaminergic therapy. Targeting the locus coeruleus-noradrenaline system may improve response inhibition deficits, with atomoxetine showing potential in some patients. Predicting treatment response and patient selection for atomoxetine therapy based on locus coeruleus integrity is crucial for optimizing therapeutic outcomes.
Article
Neurosciences
Nanna Bertin Markussen, Rasmus West Knopper, Stine Hasselholt, Christian Stald Skoven, Jens Randel Nyengaard, Leif Ostergaard, Brian Hansen
Summary: The Locus Coeruleus (LC) is a brainstem region that supplies noradrenaline to key brain structures and affects various behaviors and physiological phenomena. Its dysfunction may play a role in neurodegenerative diseases. Animal models with LC dysfunction are essential for understanding its function and role in diseases.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Critical Care Medicine
Karen-Amanda Irvine, Christopher M. Peters, Elena M. Vazey, Adam R. Ferguson, J. David Clark
Summary: The disruption of endogenous pain control mechanisms, particularly the descending pain inhibition, has been associated with various forms of pain, including chronic pain following traumatic brain injury (TBI). This study explored the potential of selectively stimulating neurons in the locus coeruleus (LC), the key noradrenergic nucleus involved in descending pain inhibition, to reduce nociception after TBI. The findings suggested that directly stimulating the LC could alleviate both early and late manifestations of dysfunctional endogenous pain regulation. Therefore, clinical approaches targeting descending pain circuits may hold promise in alleviating pain in individuals with TBI.
JOURNAL OF NEUROTRAUMA
(2022)
Article
Biology
Juan Carlos Cerpa, Alessandro Piccin, Margot Dehove, Marina Lavigne, Eric J. Kremer, Mathieu Wolff, Shauna L. Parkes, Etienne Coutureau
Summary: Organisms need to track the relationship between actions and consequences in order to make decisions, which relies on circuits in the brain. There is functional heterogeneity within certain areas of the brain in rodents. Neuromodulatory agents play a crucial role in prefrontal functions and behavioral flexibility.
Article
Biology
Thomas Pfeffer, Christian Keitel, Daniel S. Kluger, Anne Keitel, Alena Russmann, Gregor Thut, Tobias H. Donner, Joachim Gross, Ole Jensen
Summary: This study provides a comprehensive explanation of the relationship between arousal and neuronal population activity in the human brain, revealing a higher specificity of arousal effects on different components of neural activity and across cortical regions. The study also identifies a cascade of effects relative to the timing of spontaneous pupil dilations, suggesting a temporal relationship between arousal and cortical activity.
Article
Geriatrics & Gerontology
Roy W. E. van Hooren, Frans R. J. Verhey, Inez H. G. B. Ramakers, Willemijn J. Jansen, Heidi I. L. Jacobs
Summary: The study found that higher levels of noradrenaline metabolite (MHPG) were associated with lower cortical thickness and hippocampal volume, possibly under low A beta 42 and high phosphorylated tau levels. These associations remained significant even after adding APOE-E4 or cognitive status as covariates. The results suggest that MHPG and AD pathology together contribute to neurodegeneration, possibly before significant amyloidosis, highlighting the potential importance of the noradrenergic system in early detection of AD-related processes.
NEUROBIOLOGY OF AGING
(2021)
Review
Neurosciences
Alison M. Luckey, Ian H. Robertson, Brian Lawlor, Anusha Mohan, Sven Vanneste
Summary: This article revisits the vulnerability of females to Alzheimer's disease and proposes a new hypothesis on the role of sex differences in the locus coeruleus-noradrenaline system. It highlights the importance of investigating the locus coeruleus morphology, estrogen levels, neuroinflammation, blood-brain barrier permeability, APOE epsilon 4 polymorphism, and cognitive reserve in relation to AD vulnerability. The article suggests that a precision medicine approach may be necessary to develop distinct treatments for females and males with Alzheimer's disease.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Editorial Material
Neurosciences
O. Eschenko, P. B. Mello-Carpes, N. Hansen
Article
Neurosciences
Ricardo M. Neves, Silvia van Keulen, Mingyu Yang, Nikos K. Logothetis, Oxana Eschenko
JOURNAL OF NEUROPHYSIOLOGY
(2018)
Article
Neurosciences
Nelson K. Totah, Ricardo M. Neves, Stefano Panzeri, Nikos K. Logothetis, Oxana Eschenko
Review
Neurosciences
Nelson K. B. Totah, Nikos K. Logothetis, Oxana Eschenko
Article
Neurosciences
Mingyu Yang, Nikos K. Logothetis, Oxana Eschenko
JOURNAL OF NEUROSCIENCE
(2019)
Review
Neurosciences
Gina R. Poe, Stephen Foote, Oxana Eschenko, Joshua P. Johansen, Sebastien Bouret, Gary Aston-Jones, Carolyn W. Harley, Denise Manahan-Vaughan, David Weinshenker, Rita Valentino, Craig Berridge, Daniel J. Chandler, Barry Waterhouse, Susan J. Sara
NATURE REVIEWS NEUROSCIENCE
(2020)
Article
Neurosciences
Ernesto Duran, Mingyu Yang, Ricardo Neves, Nikos K. Logothetis, Oxana Eschenko
Summary: LC phasic activation significantly modulates prefrontal population dynamics by regulating neuronal excitability, leading to altered excitatory states in the mPFC and potentially promoting synaptic plasticity and memory consolidation.
Article
Multidisciplinary Sciences
Mingyu Yang, Nikos K. Logothetis, Oxana Eschenko
Summary: The study shows that microstimulation of the locus coeruleus (LC) in rats can attenuate the Acoustic Startle Response (ASR) by inducing cortical arousal, with potential involvement of ascending projections and brainstem modulation in the regulatory process. Further investigation is needed to understand the underlying neurophysiological mechanisms.
SCIENTIFIC REPORTS
(2021)
Article
Neurosciences
Nelson K. Totah, Nikos K. Logothetis, Oxana Eschenko
Summary: The brainstem noradrenergic locus coeruleus (LC) and the prefrontal cortex (PFC) are reciprocally connected, allowing for mutual influence. Transient increases in PFC high y power may indicate changes in LC activity. Synchronized PFC neuronal spiking during high y transients may provide a new mode of top-down control over the LC.
JOURNAL OF NEUROPHYSIOLOGY
(2021)
Meeting Abstract
Clinical Neurology
A. Volnova, N. Kurzina, A. Belskaya, A. Gromova, R. Gainetdinov, O. Eschenko
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Neurosciences
Anna Kabanova, Elena Cavani, Nikos K. Logothetis, Oxana Eschenko
Summary: The locus coeruleus norepinephrine (LC-NE) system plays a modulatory role in various functions, and dysfunction of this system can lead to neurological and neurodegenerative conditions. In this study, the researchers used viral-vector and gene-engineering technology to target and control LC-NE neurons in adult male rats. The results emphasize the importance of considering the actual fraction of manipulated neurons when interpreting the outcomes of functional connectivity studies.
Article
Clinical Neurology
Alexander J. Ehrenberg, Michael A. Kelberman, Kathy Y. Liu, Martin J. Dahl, David Weinshenker, Neus Falgas, Shubir Dutt, Mara Mather, Mareike Ludwig, Matthew J. Betts, Joseph R. Winer, Stefan Teipel, Alexandra J. Weigand, Oxana Eschenko, Dorothea Haemmerer, Marina Leiman, Scott E. Counts, James M. Shine, Ian H. Robertson, Allan I. Levey, Elisa Lancini, Gowoon Son, Chrisoph Schneider, Maxime Van Egroo, Claudio Liguori, Qin Wang, Elena M. Vazey, Federico Rodriguez-Porcel, Lena Haag, Mark W. Bondi, Sven Vanneste, Whitney M. Freeze, Yeo-Jin Yi, Mihovil Maldinov, Jennifer Gatchel, Abhijit Satpati, Claudio Babiloni, William S. Kremen, Robert Howard, Heidi I. L. Jacobs, Lea T. Grinberg
Summary: The nuclei in the neuromodulatory subcortical system (NSS) play critical roles in survival, hedonic tone, and homeostasis. Degeneration of NSS occurs early in the pathogenesis of Alzheimer's disease (AD), even before the emergence of memory dysfunction and cortical lesions. NSS dysfunction and degeneration are associated with the behavioral and neuropsychiatric symptoms observed in early AD stages. Experimental studies suggest that NSS degeneration contributes to the neuroinflammatory status and disease progression in AD. It is important to understand the mechanisms underlying NSS vulnerability and the clinical progression of NSS changes in AD.
ALZHEIMERS & DEMENTIA
(2023)
Article
Multidisciplinary Sciences
Ernesto Duran, Martina Pandinelli, Nikos K. Logothetis, Oxana Eschenko
Summary: The evaluation of the effects of noradrenergic drugs on cognition is highly important. Norepinephrine plays a crucial role in cognitive processes and memory consolidation during sleep. By altering noradrenergic transmission, this study found that learning rates decreased and hippocampal activity was significantly reduced in drug-treated rats. The pharmacological alteration of noradrenergic transmission resulted in a suboptimal brain state for memory consolidation.
SCIENTIFIC REPORTS
(2023)
Article
Neurosciences
Hao Mei, Nikos K. Logothetis, Oxana Eschenko