scholarly journals A Locus Coeruleus- dorsal CA1 dopaminergic circuit modulates memory linking

2021 ◽  
Author(s):  
Ananya Chowdhury ◽  
Alessandro Luchetti ◽  
Giselle Fernandes ◽  
Daniel Almeida Filho ◽  
George Kastellakis ◽  
...  
Keyword(s):  
Locus Coeruleus ◽  
Memory Formation ◽  
Temporary Increase ◽  
Contextual Memory ◽  
The Stability ◽  
The Brain ◽  
Permissive Role

Individual memories are often linked so that the recall of one triggers the recall of another. For example, contextual memories acquired close in time can be linked, and this is known to depend on temporary increase in excitability that drive the overlap between dorsal CA1 (dCA1) hippocampal ensembles encoding the linked memories. Here, we show that the Locus Coeruleus (LC) cells projecting to dCA1 have a key permissive role in contextual memory linking, without affecting contextual memory formation, and that this effect is mediated by dopamine and not by noradrenaline. Additionally, we found that LC to dCA1 projecting neurons modulate the excitability of dCA1 neurons, and the extent of overlap between dCA1 memory ensembles, as well as the stability of coactivity patterns within these ensembles. This discovery of a neuromodulatory system that specifically affects memory linking without affecting memory formation, reveals a fundamental separation between the brain mechanisms that modulate these two distinct processes.

scholarly journals Noradrenergic projections from the locus coeruleus to the amygdala constrain auditory fear memory reconsolidation

2020 ◽  
Author(s):  
Josue Haubrich ◽  
Matteo Bernabo ◽  
Karim Nader
Keyword(s):  
Boundary Condition ◽  
Boundary Conditions ◽  
Locus Coeruleus ◽  
Molecular Mechanisms ◽  
Fear Memory ◽  
Memory Formation ◽  
Memory Reconsolidation ◽  
Memory Encoding ◽  
Memory Strength ◽  
The Brain

ABSTRACTMemory reconsolidation is a fundamental plasticity process in the brain that allows established memories to be changed or erased. However, certain boundary conditions limit the parameters under which memories can be made plastic. Strong memories do not destabilize, for instance, although why they are resilient is mostly unknown. Here, we extend the understanding of the mechanisms implicated in reconsolidation-resistant memories by investigating the hypothesis that specific modulatory signals shape memory formation into a state that lacks lability. We find that the activation of the noradrenaline-locus coeruleus system (NOR-LC) during strong fear memory encoding increases molecular mechanisms of stability at the expense of lability in the amygdala. Preventing the NOR-LC from modulating strong fear encoding results in the formation of memories that can undergo reconsolidation within the amygdala and thus are vulnerable to post-reactivation interference. Thus, the memory strength boundary condition on reconsolidation is set at the time of encoding by the action of the NOR-LC.

scholarly journals Noradrenergic projections from the locus coeruleus to the amygdala constrain fear memory reconsolidation

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Josué Haubrich ◽  
Matteo Bernabo ◽  
Karim Nader
Keyword(s):  
Boundary Condition ◽  
Boundary Conditions ◽  
Locus Coeruleus ◽  
Molecular Mechanisms ◽  
Fear Memory ◽  
Memory Formation ◽  
Memory Reconsolidation ◽  
Memory Encoding ◽  
Memory Strength ◽  
The Brain

Memory reconsolidation is a fundamental plasticity process in the brain that allows established memories to be changed or erased. However, certain boundary conditions limit the parameters under which memories can be made plastic. Strong memories do not destabilize, for instance, although why they are resilient is mostly unknown. Here, we investigated the hypothesis that specific modulatory signals shape memory formation into a state that is reconsolidation-resistant. We find that the activation of the noradrenaline-locus coeruleus system (NOR-LC) during strong fear memory encoding increases molecular mechanisms of stability at the expense of lability in the amygdala of rats. Preventing the NOR-LC from modulating strong fear encoding results in the formation of memories that can undergo reconsolidation within the amygdala and thus are vulnerable to post-reactivation interference. Thus, the memory strength boundary condition on reconsolidation is set at the time of encoding by the action of the NOR-LC.

scholarly journals Comparisons of neuroinflammation, microglial activation, and degeneration of the locus coeruleus-norepinephrine system in APP/PS1 and aging mice

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Song Cao ◽  
Daniel W. Fisher ◽  
Guadalupe Rodriguez ◽  
Tian Yu ◽  
Hongxin Dong
Keyword(s):  
Spinal Cord ◽  
Locus Coeruleus ◽  
Microglial Activation ◽  
Healthy Aging ◽  
Cell Types ◽  
Norepinephrine System ◽  
Protective Processes ◽  
The Central Nervous System ◽  
Brain And Spinal Cord ◽  
The Brain

Abstract Background The role of microglia in Alzheimer’s disease (AD) pathogenesis is becoming increasingly important, as activation of these cell types likely contributes to both pathological and protective processes associated with all phases of the disease. During early AD pathogenesis, one of the first areas of degeneration is the locus coeruleus (LC), which provides broad innervation of the central nervous system and facilitates norepinephrine (NE) transmission. Though the LC-NE is likely to influence microglial dynamics, it is unclear how these systems change with AD compared to otherwise healthy aging. Methods In this study, we evaluated the dynamic changes of neuroinflammation and neurodegeneration in the LC-NE system in the brain and spinal cord of APP/PS1 mice and aged WT mice using immunofluorescence and ELISA. Results Our results demonstrated increased expression of inflammatory cytokines and microglial activation observed in the cortex, hippocampus, and spinal cord of APP/PS1 compared to WT mice. LC-NE neuron and fiber loss as well as reduced norepinephrine transporter (NET) expression was more evident in APP/PS1 mice, although NE levels were similar between 12-month-old APP/PS1 and WT mice. Notably, the degree of microglial activation, LC-NE nerve fiber loss, and NET reduction in the brain and spinal cord were more severe in 12-month-old APP/PS1 compared to 12- and 24-month-old WT mice. Conclusion These results suggest that elevated neuroinflammation and microglial activation in the brain and spinal cord of APP/PS1 mice correlate with significant degeneration of the LC-NE system.

scholarly journals Synaptic propagation in neuronal networks with finite-support space dependent coupling

2020 ◽  
Author(s):  
Ricardo Erazo Toscano ◽  
Remus Osan
Keyword(s):  
Time Constant ◽  
Sensory Processing ◽  
Traveling Waves ◽  
Traveling Wave ◽  
Neuronal Networks ◽  
Evolution Equations ◽  
Network Connectivity ◽  
Space Constant ◽  
The Stability ◽  
The Brain

1AbstractTraveling waves of electrical activity are ubiquitous in biological neuronal networks. Traveling waves in the brain are associated with sensory processing, phase coding, and sleep. The neuron and network parameters that determine traveling waves’ evolution are synaptic space constant, synaptic conductance, membrane time constant, and synaptic decay time constant. We used an abstract neuron model to investigate the propagation characteristics of traveling wave activity. We formulated a set of evolution equations based on the network connectivity parameters. We numerically investigated the stability of the traveling wave propagation with a series of perturbations with biological relevance.

scholarly journals The specification of noradrenergic locus coeruleus (LC) neurones depends on bone morphogenetic proteins (BMPs)

Development ◽  
2002 ◽  
Vol 129 (4) ◽  
pp. 983-991 ◽  
Author(s):  
Astrid Vogel-Höpker ◽  
Hermann Rohrer
Keyword(s):  
Transcription Factors ◽  
Locus Coeruleus ◽  
Bone Morphogenetic Proteins ◽  
Chick Embryos ◽  
Dorsal Midline ◽  
Neural Crest Development ◽  
Roof Plate ◽  
Rhombic Lip ◽  
The Brain

The role of BMPs in the development of the major noradrenergic centre of the brain, the locus coeruleus (LC), was investigated. LC generation is reflected by initial expression of the transcription factors Phox2a and Phox2b in dorsal rhombomere1 (r1), followed by expression of dopamine-β-hydroxylase and tyrosine hydroxylase. Bmp5 is expressed in the dorsal neuroepithelium in proximity to Phox2-expressing cells. BMP inhibition in stage 10 chick embryos resulted in the lack of LC neurones or in their generation at the dorsal midline, and loss of roof plate and rhombic lip, but it did not affect neural crest development. These results reveal late essential BMP functions in the specification of dorsal neuronal phenotypes in r1, including LC neurones, and in the development of dorsal midline structures.

scholarly journals Glymphatic System in the Central Nervous System, a Novel Therapeutic Direction Against Brain Edema After Stroke

2021 ◽  
Vol 13 ◽  
Author(s):  
Xiangyue Zhou ◽  
Youwei Li ◽  
Cameron Lenahan ◽  
Yibo Ou ◽  
Minghuan Wang ◽  
...  
Keyword(s):  
Brain Edema ◽  
Brain Tissue ◽  
Molecular Mechanisms ◽  
Glymphatic System ◽  
System A ◽  
Function Recovery ◽  
The Central Nervous System ◽  
The Stability ◽  
The Brain

Stroke is the destruction of brain function and structure, and is caused by either cerebrovascular obstruction or rupture. It is a disease associated with high mortality and disability worldwide. Brain edema after stroke is an important factor affecting neurologic function recovery. The glymphatic system is a recently discovered cerebrospinal fluid (CSF) transport system. Through the perivascular space and aquaporin 4 (AQP4) on astrocytes, it promotes the exchange of CSF and interstitial fluid (ISF), clears brain metabolic waste, and maintains the stability of the internal environment within the brain. Excessive accumulation of fluid in the brain tissue causes cerebral edema, but the glymphatic system plays an important role in the process of both intake and removal of fluid within the brain. The changes in the glymphatic system after stroke may be an important contributor to brain edema. Understanding and targeting the molecular mechanisms and the role of the glymphatic system in the formation and regression of brain edema after stroke could promote the exclusion of fluids in the brain tissue and promote the recovery of neurological function in stroke patients. In this review, we will discuss the physiology of the glymphatic system, as well as the related mechanisms and therapeutic targets involved in the formation of brain edema after stroke, which could provide a new direction for research against brain edema after stroke.

scholarly journals Locus Coeruleus Magnetic Resonance Imaging in Neurological Diseases

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Alessandro Galgani ◽  
Francesco Lombardo ◽  
Daniele Della Latta ◽  
Nicola Martini ◽  
Ubaldo Bonuccelli ◽  
...  
Keyword(s):  
Locus Coeruleus ◽  
Neurological Disorders ◽  
Potential Role ◽  
Neurological Diseases ◽  
Mri Findings ◽  
Promising Tool ◽  
Experimental Tool ◽  
Early Biomarker ◽  
The Brain

Abstract Purpose of Review Locus coeruleus (LC) is the main noradrenergic nucleus of the brain, and its degeneration is considered to be key in the pathogenesis of neurodegenerative diseases. In the last 15 years,MRI has been used to assess LC in vivo, both in healthy subjects and in patients suffering from neurological disorders. In this review, we summarize the main findings of LC-MRI studies, interpreting them in light of preclinical and histopathological data, and discussing its potential role as diagnostic and experimental tool. Recent findings LC-MRI findings were largely in agreement with neuropathological evidences; LC signal showed to be not significantly affected during normal aging and to correlate with cognitive performances. On the contrary, a marked reduction of LC signal was observed in patients suffering from neurodegenerative disorders, with specific features. Summary LC-MRI is a promising tool, which may be used in the future to explore LC pathophysiology as well as an early biomarker for degenerative diseases.

scholarly journals Metabolic learning and memory formation by the brain influence systemic metabolic homeostasis

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Yumin Zhang ◽  
Gang Liu ◽  
Jingqi Yan ◽  
Yalin Zhang ◽  
Bo Li ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Memory Formation ◽  
Metabolic Homeostasis ◽  
The Brain

Increased Noradrenergic Neurotransmission to a Pain Facilitatory Area of the Brain Is Implicated in Facilitation of Chronic Pain

2015 ◽  
Vol 123 (3) ◽  
pp. 642-653 ◽  
Author(s):  
Isabel Martins ◽  
Paulina Carvalho ◽  
Martin G. de Vries ◽  
Armando Teixeira-Pinto ◽  
Steven P. Wilson ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Locus Coeruleus ◽  
Camp Response Element Binding ◽  
In Vivo Microdialysis ◽  
Reticular Nucleus ◽  
Analgesic Effects ◽  
Inhibitory Function ◽  
Noradrenaline Reuptake ◽  
The Brain

Abstract Background: Noradrenaline reuptake inhibitors are known to produce analgesia through a spinal action but they also act in the brain. However, the action of noradrenaline on supraspinal pain control regions is understudied. The authors addressed the noradrenergic modulation of the dorsal reticular nucleus (DRt), a medullary pronociceptive area, in the spared nerve injury (SNI) model of neuropathic pain. Methods: The expression of the phosphorylated cAMP response element-binding protein (pCREB), a marker of neuronal activation, was evaluated in the locus coeruleus and A5 noradrenergic neurons (n = 6 rats/group). pCREB was studied in noradrenergic DRt-projecting neurons retrogradely labeled in SNI animals (n = 3). In vivo microdialysis was used to measure noradrenaline release in the DRt on nociceptive stimulation or after DRt infusion of clonidine (n = 5 to 6 per group). Pharmacology, immunohistochemistry, and western blot were used to study α-adrenoreceptors in the DRt (n = 4 to 6 per group). Results: pCREB expression significantly increased in the locus coeruleus and A5 of SNI animals, and most noradrenergic DRt-projecting neurons expressed pCREB. In SNI animals, noradrenaline levels significantly increased on pinprick (mean ± SD, 126 ± 14%; P = 0.025 vs. baseline) and acetone stimulation (mean ± SD, 151 ± 12%; P < 0.001 vs. baseline), and clonidine infusion showed decreased α2-mediated inhibitory function. α1-adrenoreceptor blockade decreased nociceptive behavioral responses in SNI animals. α2-adrenoreceptor expression was not altered. Conclusions: Chronic pain induces brainstem noradrenergic activation that enhances descending facilitation from the DRt. This suggests that antidepressants inhibiting noradrenaline reuptake may enhance pain facilitation from the brain, counteracting their analgesic effects at the spinal cord.

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