scholarly journals The use of viral gene transfer in studies of brainstem noradrenergic and serotonergic neurons

2009 ◽  
Vol 364 (1529) ◽  
pp. 2565-2576 ◽  
Author(s):  
S. Kasparov ◽  
A. G. Teschemacher
Keyword(s):  
Viral Vectors ◽  
Pyramidal Neurons ◽  
Viral Gene ◽  
Volume Transmission ◽  
Neuronal Populations ◽  
Central Neurons ◽  
Wide Range ◽  
Cortical Pyramidal Neurons ◽  
The Brain

In contrast to some other neuronal populations, for example hippocampal or cortical pyramidal neurons, mechanisms of synaptic integration and transmitter release in central neurons that contain noradrenaline (NA) and serotonin (5HT) are not well understood. These cells, crucial for a wide range of autonomic and behavioural processes, have long un-myelinated axons with hundreds of varicosities where transmitters are synthesized and released. Both seem to signal mostly in ‘volume transmission’ mode. Very little is known about the rules that apply to this type of transmission in the brain and the factors that regulate the release of NA and 5HT. We discuss some of our published studies and more recent experiments in which viral vectors were used to investigate the physiology of these neuronal populations. We also focus on currently unresolved issues concerning the mechanism of volume transmission by NA and 5HT in the brain. We suggest that clarifying the role of astroglia in this process could be essential for our understanding of central noradrenergic and 5HT signalling.

scholarly journals The Role of Dendritic Signaling in the Anesthetic Suppression of Consciousness

2015 ◽  
Vol 122 (6) ◽  
pp. 1415-1431 ◽  
Author(s):  
Kaspar Meyer
Keyword(s):  
Pyramidal Neurons ◽  
Physiological Mechanism ◽  
Anatomical Site ◽  
General Anesthetics ◽  
Top Down ◽  
Theoretical Frameworks ◽  
Cortical Pyramidal Neurons ◽  
Sensory Cortices ◽  
The Brain

Abstract Despite considerable progress in the identification of the molecular targets of general anesthetics, it remains unclear how these drugs affect the brain at the systems level to suppress consciousness. According to recent proposals, anesthetics may achieve this feat by interfering with corticocortical top–down processes, that is, by interrupting information flow from association to early sensory cortices. Such a view entails two immediate questions. First, at which anatomical site, and by virtue of which physiological mechanism, do anesthetics interfere with top–down signals? Second, why does a breakdown of top–down signaling cause unconsciousness? While an answer to the first question can be gleaned from emerging neurophysiological evidence on dendritic signaling in cortical pyramidal neurons, a response to the second is offered by increasingly popular theoretical frameworks that place the element of prediction at the heart of conscious perception.

scholarly journals Cholinergic modulation of sensory processing in awake mouse cortex

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Javier Jimenez-Martin ◽  
Daniil Potapov ◽  
Kay Potapov ◽  
Thomas Knöpfel ◽  
Ruth M. Empson
Keyword(s):  
Pyramidal Neurons ◽  
Brain Activity ◽  
Critical Role ◽  
Sensory Information ◽  
Sensory Stimulation ◽  
Cholinergic Modulation ◽  
Neuronal Populations ◽  
Mouse Cortex ◽  
Cortical Pyramidal Neurons ◽  
Sensory Evoked

AbstractCholinergic modulation of brain activity is fundamental for awareness and conscious sensorimotor behaviours, but deciphering the timing and significance of acetylcholine actions for these behaviours is challenging. The widespread nature of cholinergic projections to the cortex means that new insights require access to specific neuronal populations, and on a time-scale that matches behaviourally relevant cholinergic actions. Here, we use fast, voltage imaging of L2/3 cortical pyramidal neurons exclusively expressing the genetically-encoded voltage indicator Butterfly 1.2, in awake, head-fixed mice, receiving sensory stimulation, whilst manipulating the cholinergic system. Altering muscarinic acetylcholine function re-shaped sensory-evoked fast depolarisation and subsequent slow hyperpolarisation of L2/3 pyramidal neurons. A consequence of this re-shaping was disrupted adaptation of the sensory-evoked responses, suggesting a critical role for acetylcholine during sensory discrimination behaviour. Our findings provide new insights into how the cortex processes sensory information and how loss of acetylcholine, for example in Alzheimer’s Disease, disrupts sensory behaviours.

scholarly journals Functional dichotomy in spinal- vs prefrontal-projecting locus coeruleus modules splits descending noradrenergic analgesia from ascending aversion and anxiety in rats

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Stefan Hirschberg ◽  
Yong Li ◽  
Andrew Randall ◽  
Eric J Kremer ◽  
Anthony E Pickering
Keyword(s):  
Locus Coeruleus ◽  
Viral Vectors ◽  
Spontaneous Pain ◽  
Pain Model ◽  
Axon Terminals ◽  
Neuronal Populations ◽  
Functional Organisation ◽  
Neuropathic Pain Model ◽  
Brain And Spinal Cord ◽  
The Brain

The locus coeruleus (LC) projects throughout the brain and spinal cord and is the major source of central noradrenaline. It remains unclear whether the LC acts functionally as a single global effector or as discrete modules. Specifically, while spinal-projections from LC neurons can exert analgesic actions, it is not known whether they can act independently of ascending LC projections. Using viral vectors taken up at axon terminals, we expressed chemogenetic actuators selectively in LC neurons with spinal (LC:SC) or prefrontal cortex (LC:PFC) projections. Activation of the LC:SC module produced robust, lateralised anti-nociception while activation of LC:PFC produced aversion. In a neuropathic pain model, LC:SC activation reduced hind-limb sensitisation and induced conditioned place preference. By contrast, activation of LC:PFC exacerbated spontaneous pain, produced aversion and increased anxiety-like behaviour. This independent, contrasting modulation of pain-related behaviours mediated by distinct noradrenergic neuronal populations provides evidence for a modular functional organisation of the LC.

scholarly journals Focused Ultrasound for Increased Delivery of Intranasal DNA Nanoparticles to Rat Brain

2018 ◽  
Author(s):  
Barbara L. Waszczak ◽  
Nathan McDannold ◽  
Mark J. Cooper
Keyword(s):  
Transgene Expression ◽  
Viral Vectors ◽  
Focused Ultrasound ◽  
Route Of Administration ◽  
Viral Gene ◽  
Dna Nanoparticles ◽  
Non Invasive ◽  
Treatment Conditions ◽  
Cellular Transfection ◽  
The Brain

We will investigate whether focused ultrasound (FUS) can increase delivery to the brain of a non-viral gene vector given by the intranasal route of administration. Aim 1 will examine different FUS treatment conditions to determine if FUS can increase total plasmid DNA nanoparticle (NP) delivery and transgene expression in the sonicated regions, the rat substantia nigra and striatum, two brain areas involved in Parkinson's Disease (PD). Aim 2 will test whether FUS improves tissue penetration and alters cellular transfection patterns in the sonicated regions following intranasal doses of DNA NPs. If successful, FUS may enable agents with poor capabilities of crossing the blood-brain barrier (BBB), e.g. neurotrophic factors, viral and non-viral vectors encoding them, to become disease-altering therapies by a non-invasive route of administration.

scholarly journals An extended toolkit for production and use of RVdG-CVS-N2c rabies viral vectors uncovers hidden hippocampal connections

2021 ◽  
Author(s):  
Anton Sumser ◽  
Maximilian Joesch ◽  
Peter Jonas ◽  
Yoav Ben-Simon
Keyword(s):  
Viral Vectors ◽  
Molecular Tools ◽  
Cell Type ◽  
Large Collection ◽  
Neuronal Connectivity ◽  
Retrograde Labeling ◽  
Neuronal Populations ◽  
Wide Range ◽  
Cell Type Specific ◽  
Cortical Microcircuit

From the large collection of molecular tools used to investigate neuronal connectivity, envA-pseudotyped rabies viral vectors (RVdGenvA) uniquely enable cell-type specific, trans-synaptic retrograde labeling. However, widespread use of the powerful and flexible method is to date hindered by low-yield and cumbersome production pipelines. Here, we report the development of new cell lines, which significantly reduce production time while increasing viral titer and eliminating background contamination from native-coat particles. We further show that RVdGenvA-CVS-N2c vectors produced using this system retain their enhanced retrograde-trafficking when compared with SAD-B19 vectors, allowing us to uncover undescribed cortico-hippocampal connections and to monitor activity in a cortical microcircuit of behaving animals. Along with new suites of AAV and RVdG-CVS-N2c vectors, developed to enable retrograde labeling from a wide range of neuronal populations and tailored for diverse experimental requirements, we present here an optimal system for mapping, manipulating and imaging of neuronal circuits.

scholarly journals Gut and Brain: Investigating Physiological and Pathological Interactions Between Microbiota and Brain to Gain New Therapeutic Avenues for Brain Diseases

2021 ◽  
Vol 15 ◽  
Author(s):  
Gabriele Deidda ◽  
Manuele Biazzo
Keyword(s):  
Gut Microbiota ◽  
Therapeutic Strategy ◽  
Brain Diseases ◽  
Microbial Populations ◽  
Normal Brain ◽  
Neuronal Populations ◽  
Brain Physiology ◽  
Pathological Conditions ◽  
The Brain

Brain physiological functions or pathological dysfunctions do surely depend on the activity of both neuronal and non-neuronal populations. Nevertheless, over the last decades, compelling and fast accumulating evidence showed that the brain is not alone. Indeed, the so-called “gut brain,” composed of the microbial populations living in the gut, forms a symbiotic superorganism weighing as the human brain and strongly communicating with the latter via the gut–brain axis. The gut brain does exert a control on brain (dys)functions and it will eventually become a promising valuable therapeutic target for a number of brain pathologies. In the present review, we will first describe the role of gut microbiota in normal brain physiology from neurodevelopment till adulthood, and thereafter we will discuss evidence from the literature showing how gut microbiota alterations are a signature in a number of brain pathologies ranging from neurodevelopmental to neurodegenerative disorders, and how pre/probiotic supplement interventions aimed to correct the altered dysbiosis in pathological conditions may represent a valuable future therapeutic strategy.

The Correlation Between Ischemic Stroke and Thrombosis by Nanoscale Biomarker Analysis

2020 ◽  
Vol 16 (5) ◽  
pp. 676-684
Author(s):  
Guoqing Wang ◽  
Xiangpeng Shen ◽  
Qiangyuan Tian ◽  
Thangavel Lakshmipriya ◽  
Subash C.B. Gopinath
Keyword(s):  
Ischemic Stroke ◽  
Factor Ix ◽  
Clotting Factor ◽  
Clinical Biomarkers ◽  
Wide Range ◽  
Biomarker Analysis ◽  
Highly Correlated ◽  
Brain Artery ◽  
The Brain

Ischemic stroke, which is the fifth leading cause of death, is an attack in the brain due to blockage of a brain artery. It occurs when a sudden loss of blood flow to the brain leads to a reduction in the oxygen supply. A wide range of reasons have been found for ischemic stroke, including high blood pressure and associated thrombosis. Suitable biomarker analysis followed by proper treatment helps to prevent ischemic stroke. An aptamer is an artificial antibody generated against various clinical biomarkers from a smaller molecule of a whole cell. Recently, several researchers conducted biomarker analysis for ischemic stroke using aptamers. Furthermore, factor IX, which is a blood clotting factor, is highly correlated with thrombosis and plays a role in ischemic stroke. In this review, we summarized the potential role of aptamers in ischemic stroke by nanoscale analysis, and factor IX was the distinct focus of this review.

scholarly journals Dissociated Expression of Mitochondrial and Cytosolic Creatine Kinases in the Human Brain: A New Perspective on the Role of Creatine in Brain Energy Metabolism

2013 ◽  
Vol 33 (8) ◽  
pp. 1295-1306 ◽  
Author(s):  
Matthew TJ Lowe ◽  
Eric H Kim ◽  
Richard LM Faull ◽  
David L Christie ◽  
Henry J Waldvogel
Keyword(s):  
Energy Metabolism ◽  
Human Brain ◽  
High Energy ◽  
Cellular Energy ◽  
Neuronal Populations ◽  
Neurologic Function ◽  
New Perspective ◽  
The Brain ◽  
Brain Energy

The phosphocreatine/creatine kinase (PCr/CK) system in the brain is defined by the expression of two CK isozymes: the cytosolic brain-type CK (BCK) and the ubiquitous mitochondrial CK (uMtCK). The system plays an important role in supporting cellular energy metabolism by buffering adenosine triphosphate (ATP) consumption and improving the flux of high-energy phosphoryls around the cell. This system is well defined in muscle tissue, but there have been few detailed studies of this system in the brain, especially in humans. Creatine is known to be important for neurologic function, and its loss from the brain during development can lead to mental retardation. This study provides the first detailed immunohistochemical study of the expression pattern of BCK and uMtCK in the human brain. A strikingly dissociated pattern of expression was found: uMtCK was found to be ubiquitously and exclusively expressed in neuronal populations, whereas BCK was dominantly expressed in astrocytes, with a low and selective expression in neurons. This pattern indicates that the two CK isozymes are not widely coexpressed in the human brain, but rather are selectively expressed depending on the cell type. These results suggest that the brain cells may use only certain properties of the PCr/CK system depending on their energetic requirements.

Dendritic integration theory: A thalamo-cortical theory of state and content of consciousness

2020 ◽  
Vol 1 (II) ◽  
Author(s):  
Talis Bachmann ◽  
Mototaka Suzuki ◽  
Jaan Aru
Keyword(s):  
Pyramidal Neurons ◽  
Conscious Experience ◽  
Pyramidal Cells ◽  
Neural Mechanisms ◽  
Integration Theory ◽  
Thalamic Nuclei ◽  
Cortical Pyramidal Neurons ◽  
Cortical System ◽  
Work Done

The idea that the thalamo-cortical system is the crucial constituent of the neurobiological mechanisms of consciousness has a long history. For the last few decades, however, consciousness research has to a large extent overlooked the interplay between the cortex and thalamus. Here we revive an integrated view of the neurobiology of consciousness by presenting and discussing several recent major findings about the role of the thalamocortical interactions in consciousness. Based on these findings we propose a specific cellular mechanism how thalamic nuclei modulate the integration of different processing streams within single cortical pyramidal neurons. This theory is inspired by recent work done in rodents, but it integrates decades of work conducted on various species. We illustrate how this new view readily explains various properties and experimental phenomena associated with conscious experience. We discuss the implications of this idea and some of the experiments that need to be done in order to test it. Our view bridges two long-standing perspectives on the neural mechanisms of consciousness and proposes that cortical and thalamo-cortical processing interact at the level of single pyramidal cells.

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