scholarly journals Sites of Circadian Clock Neuron Plasticity Mediate Sensory Integration and Entrainment

2019 ◽  
Author(s):  
MP Fernández ◽  
HL Pettibone ◽  
CJ Roell ◽  
CE Davey ◽  
KV Huynh ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Neural Development ◽  
Sensory Integration ◽  
Neuronal Morphology ◽  
Sensory Inputs ◽  
Neuron Networks ◽  
Neuronal Remodeling ◽  
The Brain ◽  
Daily Changes ◽  
Lateral Neurons

SummaryNetworks of circadian timekeeping in the brain display marked daily changes in neuronal morphology. In Drosophila melanogaster, the striking daily structural remodeling of the dorsal medial termini of the small ventral lateral neurons has long been hypothesized to mediate endogenous circadian timekeeping. To test this model, we have specifically abrogated these sites of daily neuronal remodeling through the reprogramming of neural development and assessed the effects on circadian timekeeping and clock outputs. Remarkably, the loss of these sites has no measurable effects on endogenous circadian timekeeping or on any of the major output functions of the small ventral lateral neurons. Rather, their loss reduces sites of glutamatergic sensory neurotransmission that normally encodes naturalistic time-cues from the environment. These results support an alternative model: structural plasticity in critical clock neurons is the basis for proper integration of light and temperature and gates sensory inputs into circadian clock neuron networks.

scholarly journals Light Dominates Peripheral Circadian Oscillations in Drosophila melanogaster During Sensory Conflict

2017 ◽  
Vol 32 (5) ◽  
pp. 423-432 ◽  
Author(s):  
Ross E. F. Harper ◽  
Maite Ogueta ◽  
Peter Dayan ◽  
Ralf Stanewsky ◽  
Joerg T. Albert
Keyword(s):  
Sensory Integration ◽  
Light Stimulus ◽  
External Input ◽  
Environmental Cues ◽  
Multiple Processes ◽  
Peripheral Clocks ◽  
Central Clock ◽  
Complex Forms ◽  
The Brain ◽  
Daily Changes

In Drosophila, as in other animals, the circadian clock is a singular entity in name and concept only. In reality, clock functions emerge from multiple processes and anatomical substrates. One distinction has conventionally been made between a central clock (in the brain) and peripheral clocks (e.g., in the gut and the eyes). Both types of clock generate robust circadian oscillations, which do not require external input. Furthermore, the phases of these oscillations remain exquisitely sensitive to specific environmental cues, such as the daily changes of light and temperature. When these cues conflict with one another, the central clock displays complex forms of sensory integration; how peripheral clocks respond to conflicting input is unclear. We therefore explored the effects of light and temperature misalignments on peripheral clocks. We show that under conflict, peripheral clocks preferentially synchronize to the light stimulus. This photic dominance requires the presence of the circadian photoreceptor, Cryptochrome.

The Circadian Clock of the Ant Camponotus floridanus Is Localized in Dorsal and Lateral Neurons of the Brain

2018 ◽  
Vol 33 (3) ◽  
pp. 255-271 ◽  
Author(s):  
Janina Kay ◽  
Pamela Menegazzi ◽  
Stephanie Mildner ◽  
Flavio Roces ◽  
Charlotte Helfrich-Förster
Keyword(s):  
Circadian Clock ◽  
Camponotus Floridanus ◽  
The Brain ◽  
Lateral Neurons

Central and Peripheral Clock Control of Circadian Feeding Rhythms

2021 ◽  
pp. 074873042110458
Author(s):  
Carson V. Fulgham ◽  
Austin P. Dreyer ◽  
Anita Nasseri ◽  
Asia N. Miller ◽  
Jacob Love ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Circadian Clock ◽  
Feeding Behavior ◽  
Molecular Clock ◽  
Fat Body ◽  
Molecular Clocks ◽  
Central Brain ◽  
Feeding Rhythms ◽  
Free Running ◽  
The Brain

Many behaviors exhibit ~24-h oscillations under control of an endogenous circadian timing system that tracks time of day via a molecular circadian clock. In the fruit fly, Drosophila melanogaster, most circadian research has focused on the generation of locomotor activity rhythms, but a fundamental question is how the circadian clock orchestrates multiple distinct behavioral outputs. Here, we have investigated the cells and circuits mediating circadian control of feeding behavior. Using an array of genetic tools, we show that, as is the case for locomotor activity rhythms, the presence of feeding rhythms requires molecular clock function in the ventrolateral clock neurons of the central brain. We further demonstrate that the speed of molecular clock oscillations in these neurons dictates the free-running period length of feeding rhythms. In contrast to the effects observed with central clock cell manipulations, we show that genetic abrogation of the molecular clock in the fat body, a peripheral metabolic tissue, is without effect on feeding behavior. Interestingly, we find that molecular clocks in the brain and fat body of control flies gradually grow out of phase with one another under free-running conditions, likely due to a long endogenous period of the fat body clock. Under these conditions, the period of feeding rhythms tracks with molecular oscillations in central brain clock cells, consistent with a primary role of the brain clock in dictating the timing of feeding behavior. Finally, despite a lack of effect of fat body selective manipulations, we find that flies with simultaneous disruption of molecular clocks in multiple peripheral tissues (but with intact central clocks) exhibit decreased feeding rhythm strength and reduced overall food intake. We conclude that both central and peripheral clocks contribute to the regulation of feeding rhythms, with a particularly dominant, pacemaker role for specific populations of central brain clock cells.

scholarly journals Non-Coding RNA in Acute Ischemic Stroke: Mechanisms, Biomarkers and Therapeutic Targets

2018 ◽  
Vol 27 (12) ◽  
pp. 1763-1777 ◽  
Author(s):  
Sheng-Wen Wang ◽  
Zhong Liu ◽  
Zhong-Song Shi
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Neural Development ◽  
Therapeutic Targets ◽  
Circular Rnas ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Cerebral Ischemic ◽  
Functional Rnas ◽  
The Brain

Non-coding RNAs (ncRNAs) are a class of functional RNAs that regulate gene expression in a post-transcriptional manner. NcRNAs include microRNAs, long non-coding RNAs and circular RNAs. They are highly expressed in the brain and are involved in the regulation of physiological and pathophysiological processes, including cerebral ischemic injury, neurodegeneration, neural development, and plasticity. Stroke is one of the leading causes of death and physical disability worldwide. Acute ischemic stroke (AIS) occurs when brain blood flow stops, and that stoppage results in reduced oxygen and glucose supply to cells in the brain. In this article, we review the latest progress on ncRNAs in relation to their implications in AIS, as well as their potential as diagnostic and prognostic biomarkers. We also review ncRNAs acting as possible therapeutic targets in future precision medicine. Finally, we conclude with a brief discussion of current challenges and future directions for ncRNAs studies in AIS, which may facilitate the translation of ncRNAs research into clinical practice to improve clinical outcome of AIS.

scholarly journals Overexpression of a Neural-specific Rho Family GTPase, cRac1B, Selectively Induces Enhanced Neuritogenesis and Neurite Branching in Primary Neurons

1998 ◽  
Vol 142 (3) ◽  
pp. 815-825 ◽  
Author(s):  
Chiara Albertinazzi ◽  
Daniela Gilardelli ◽  
Simona Paris ◽  
Renato Longhi ◽  
Ivan de Curtis
Keyword(s):  
Neural Development ◽  
Neuronal Morphology ◽  
Primary Neurons ◽  
Actin Organization ◽  
Inactive Form ◽  
Rho Family Gtpases ◽  
Neurite Formation ◽  
New Gene ◽  
Rho Family

Rho family GTPases have been implicated in cytoskeletal reorganization during neuritogenesis. We have recently identified a new gene of this family, cRac1B, specifically expressed in the chicken developing nervous system. This GTPase was overexpressed in primary neurons to study the role of cRac1B in the development of the neuronal phenotype. Overexpression of cRac1B induced an increment in the number of neurites per neuron, and dramatically increased neurite branching, whereas overexpression of the highly related and ubiquitous cRac1A GTPase did not evidently affect neuronal morphology. Furthermore, expression of an inactive form of cRac1B strikingly inhibited neurite formation. The specificity of cRac1B action observed in neurons was not observed in fibroblasts, where both GTPases produced similar effects on cell morphology and actin organization, indicating the existence of a cell type-dependent specificity of cRac1B function. Molecular dissection of cRac1B function by analysis of the effects of chimeric cRac1A/cRac1B proteins showed that the COOH-terminal portion of cRac1B is essential to induce increased neuritogenesis and neurite branching. Considering the distinctive regulation of cRac1B expression during neural development, our data strongly support an important role of cRac1B during neuritogenesis, and they uncover new mechanisms underlying the functional specificity of distinct Rho family GTPases.

scholarly journals Drosophila Fragile X Protein, DFXR, Regulates Neuronal Morphology and Function in the Brain

Neuron ◽  
2002 ◽  
Vol 34 (6) ◽  
pp. 961-972 ◽  
Author(s):  
Joannella Morales ◽  
P.Robin Hiesinger ◽  
Andrew J. Schroeder ◽  
Kazuhiko Kume ◽  
Patrik Verstreken ◽  
...  
Keyword(s):  
Fragile X ◽  
Neuronal Morphology ◽  
X Protein ◽  
And Function ◽  
The Brain

scholarly journals Generation of Vascularized Brain Organoids to Study Neurovascular Interactions

2022 ◽  
Author(s):  
Zhen-Ge Luo ◽  
Xin-Yao Sun ◽  
Xiang-Chun Ju ◽  
Yang Li ◽  
Peng-Ming Zeng ◽  
...  
Keyword(s):  
Brain Development ◽  
Neural Development ◽  
Immune Cells ◽  
Aging Process ◽  
Neural Progenitors ◽  
Brain Disorders ◽  
Specific Population ◽  
Neurovascular Interactions ◽  
The Brain

The recently developed brain organoids have been used to recapitulate the processes of brain development and related diseases. However, the lack of vasculatures, which regulate neurogenesis, brain disorders, and aging process, limits the utility of brain organoids. In this study, we induced vessel and brain organoids respectively, and then fused two types of organoids together to obtain vascularized brain organoids. The fused brain organoids were engrafted with robust vascular network-like structures, and exhibited increased number of neural progenitors, in line with the possibility that vessels regulate neural development. Fusion organoids also contained functional blood-brain-barrier (BBB)-like structures, as well as microglial cells, a specific population of immune cells in the brain. The incorporated microglia responded actively to immune stimuli to the fused brain organoids. Thus, the fusion organoids established in this study allow modeling interactions between the neuronal and non-neuronal components in vitro, in particular the vasculature and microglia niche.

scholarly journals The Circadian Clock, the Brain, and COVID-19: The Cases of Olfaction and the Timing of Sleep

2021 ◽  
pp. 074873042110312
Author(s):  
Rachel S. Herz ◽  
Erik D. Herzog ◽  
Martha Merrow ◽  
Sara B. Noya
Keyword(s):  
Ischemic Stroke ◽  
Cognitive Function ◽  
Human Brain ◽  
Circadian Clock ◽  
Clinical Data ◽  
Circadian Clocks ◽  
Olfactory Sensitivity ◽  
Daily Rhythms ◽  
Sense Of Smell ◽  
The Brain

Daily rhythms of behavior and neurophysiology are integral to the circadian clocks of all animals. Examples of circadian clock regulation in the human brain include daily rhythms in sleep-wake, cognitive function, olfactory sensitivity, and risk for ischemic stroke, all of which overlap with symptoms displayed by many COVID-19 patients. Motivated by the relatively unexplored, yet pervasive, overlap between circadian functions and COVID-19 neurological symptoms, this perspective piece uses daily variations in the sense of smell and the timing of sleep and wakefulness as illustrative examples. We propose that time-stamping clinical data and testing may expand and refine diagnosis and treatment of COVID-19.

scholarly journals Cortical state transitions and stimulus response evolve along stiff and sloppy parameter dimensions, respectively

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Adrian Ponce-Alvarez ◽  
Gabriela Mochol ◽  
Ainhoa Hermoso-Mendizabal ◽  
Jaime de la Rocha ◽  
Gustavo Deco
Keyword(s):  
Collective Behavior ◽  
Neural Population ◽  
State Transitions ◽  
Population Activity ◽  
Sensory Inputs ◽  
Stimulus Response ◽  
Spontaneous Neuronal Activity ◽  
The Brain ◽  
Shed Light ◽  
Neural Population Activity

Previous research showed that spontaneous neuronal activity presents sloppiness: the collective behavior is strongly determined by a small number of parameter combinations, defined as ‘stiff’ dimensions, while it is insensitive to many others (‘sloppy’ dimensions). Here, we analyzed neural population activity from the auditory cortex of anesthetized rats while the brain spontaneously transited through different synchronized and desynchronized states and intermittently received sensory inputs. We showed that cortical state transitions were determined by changes in stiff parameters associated with the activity of a core of neurons with low responses to stimuli and high centrality within the observed network. In contrast, stimulus-evoked responses evolved along sloppy dimensions associated with the activity of neurons with low centrality and displaying large ongoing and stimulus-evoked fluctuations without affecting the integrity of the network. Our results shed light on the interplay among stability, flexibility, and responsiveness of neuronal collective dynamics during intrinsic and induced activity.

scholarly journals Cortical state transitions and stimulus response evolve along stiff and sloppy parameter dimensions, respectively

2019 ◽  
Author(s):  
Adrián Ponce-Alvarez ◽  
Gabriela Mochol ◽  
Ainhoa Hermoso-Mendizabal ◽  
Jaime de la Rocha ◽  
Gustavo Deco
Keyword(s):  
Collective Behavior ◽  
Neural Population ◽  
State Transitions ◽  
Population Activity ◽  
Sensory Inputs ◽  
Stimulus Response ◽  
Spontaneous Neuronal Activity ◽  
The Brain ◽  
Shed Light ◽  
Neural Population Activity

SummaryPrevious research showed that spontaneous neuronal activity presents sloppiness: the collective behavior is strongly determined by a small number of parameter combinations, defined as “stiff” dimensions, while it is insensitive to many others (“sloppy” dimensions). Here, we analyzed neural population activity from the auditory cortex of anesthetized rats while the brain spontaneously transited through different synchronized and desynchronized states and intermittently received sensory inputs. We showed that cortical state transitions were determined by changes in stiff parameters associated with the activity of a core of neurons with low responses to stimuli and high centrality within the observed network. In contrast, stimulus-evoked responses evolved along sloppy dimensions associated with the activity of neurons with low centrality and displaying large ongoing and stimulus-evoked fluctuations without affecting the integrity of the network. Our results shed light on the interplay among stability, flexibility, and responsiveness of neuronal collective dynamics during intrinsic and induced activity.

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