scholarly journals Homeoprotein transduction in neurodevelopment and physiopathology

2020 ◽  
Vol 6 (44) ◽  
pp. eabc6374 ◽  
Author(s):  
Ariel A. Di Nardo ◽  
Alain Joliot ◽  
Alain Prochiantz
Keyword(s):  
Axon Guidance ◽  
Sensory Processing ◽  
Brain Plasticity ◽  
Embryonic Cell ◽  
Critical Periods ◽  
Unicellular Eukaryotes ◽  
Sexual Exchange ◽  
Autonomous Activity ◽  
Mood And Cognition ◽  
Transfer Mechanisms

Homeoproteins were originally identified for embryonic cell–autonomous transcription activity, but they also have non–cell-autonomous activity owing to transfer between cells. This Review discusses transfer mechanisms and focuses on some established functions, such as neurodevelopmental regulation of axon guidance, and postnatal critical periods of brain plasticity that affect sensory processing and cognition. Homeoproteins are present across all eukaryotes, and intercellular transfer occurs in plants and animals. Proposed functions have evolutionary relevance, such as morphogenetic activity and sexual exchange during the mating of unicellular eukaryotes, while others have physiopathological relevance, such as regulation of mood and cognition by influencing brain compartmentalization, connectivity, and plasticity. There are more than 250 known homeoproteins with conserved transfer domains, suggesting that this is a common mode of signal transduction but with many undiscovered functions.

scholarly journals Critical period regulation across multiple timescales

2020 ◽  
Vol 117 (38) ◽  
pp. 23242-23251 ◽  
Author(s):  
Rebecca K. Reh ◽  
Brian G. Dias ◽  
Charles A. Nelson ◽  
Daniela Kaufer ◽  
Janet F. Werker ◽  
...  
Keyword(s):  
Critical Period ◽  
Brain Plasticity ◽  
Gamma Oscillations ◽  
Developmental Time ◽  
Brain Regions ◽  
Inhibitory Neurons ◽  
Critical Periods ◽  
Multiple Timescales ◽  
Fast Spiking ◽  
The Impact

Brain plasticity is dynamically regulated across the life span, peaking during windows of early life. Typically assessed in the physiological range of milliseconds (real time), these trajectories are also influenced on the longer timescales of developmental time (nurture) and evolutionary time (nature), which shape neural architectures that support plasticity. Properly sequenced critical periods of circuit refinement build up complex cognitive functions, such as language, from more primary modalities. Here, we consider recent progress in the biological basis of critical periods as a unifying rubric for understanding plasticity across multiple timescales. Notably, the maturation of parvalbumin-positive (PV) inhibitory neurons is pivotal. These fast-spiking cells generate gamma oscillations associated with critical period plasticity, are sensitive to circadian gene manipulation, emerge at different rates across brain regions, acquire perineuronal nets with age, and may be influenced by epigenetic factors over generations. These features provide further novel insight into the impact of early adversity and neurodevelopmental risk factors for mental disorders.

scholarly journals The Effects of Ribavirin on Development and Reproduction: A Critical Review of Published and Unpublished Studies in Experimental Animals

1990 ◽  
Vol 9 (5) ◽  
pp. 551-561 ◽  
Author(s):  
E. Marshall Johnson
Keyword(s):  
Developmental Toxicity ◽  
Antiviral Agent ◽  
In Utero ◽  
Embryonic Cell ◽  
Congenital Defects ◽  
Treatment Level ◽  
Critical Periods ◽  
Unpublished Studies ◽  
Effective Doses ◽  
In Utero Development

The effects of the antiviral agent ribavirin on reproduction and development have been examined by several experimental means in multiple animal species. In studies designed primarily to explore its mechanism of action on in utero development, the incidence, nature, and patterns of effect were directly correlated to embryonic gestational age at the time of maternal treatment. In a detailed evaluation of the pattern of embryonic cell death, there was a clear relationship between tissue necrosis and the types of congenital defects produced at effective doses. At subthreshold treatment levels there were no abnormalities in the young or necrotic areas in the embryonic/fetal tissues examined. When the developmental toxicity of ribavirin was examined, few if any, developmental malformations were present that could be related with confidence to the test agent. Several malformed fetuses were present in the highest dose level tested in rats (10 mg/kg/day) treated by gavage from Days 6-15 of pregnancy, but none were reported in rabbits similarly treated with as much as 1.0 mg/kg per day (highest dose tested) from Days 6-18 of pregnancy. The treatment level in rats may have been associated with maternal toxicity, but this important point is not established clearly for either species. When evaluated for effects on reproduction and postnatal survival in rats, ribavirin at levels of 60 and 90 mg/kg/day produced statistically significantly and/or clearly dose-related increased incidences of fetal resorptions, abnormalities, and reduced postnatal survival. Pregnant baboons given ribavirin orally at submaternally toxic levels of 60 or 120 mg/kg per day during critical periods of differentiation and organogenesis were reported to have produced no adverse effects on in utero development.

scholarly journals Synapse-selective control of cortical maturation and plasticity engages an interneuron-autonomous synaptic switch

2018 ◽  
Author(s):  
Adema Ribic ◽  
Michael C. Crair ◽  
Thomas Biederer
Keyword(s):  
Visual Cortex ◽  
Critical Period ◽  
Visual Experience ◽  
Cortical Plasticity ◽  
Brain Plasticity ◽  
Cortical Inhibition ◽  
Specific Cell ◽  
List Type ◽  
Critical Periods ◽  
Age Related

HighlightsThe synaptogenic molecule SynCAM 1 is selectively regulated by visual experienceSynCAM 1 controls thalamic input onto cortical Parvalbumin (PV+) interneuronsPV+-specific knockdown of SynCAM 1 arrests maturation of cortical inhibitionThalamic excitation onto PV+ interneurons is essential for critical period closureeTOC BlurbRibic et al. show that network plasticity in both young and adult cortex is restricted by the synapse organizing molecule SynCAM 1. On a cellular level, it functions in Parvalbumin-positive interneurons to recruit thalamocortical terminals. This controls the maturation of inhibitory drive and restricts plasticity in the cortex. These results reveal the synaptic locus of cortical plasticity and identify the first cell-autonomous synaptic factor for closure of cortical critical periods.SummaryBrain plasticity peaks early in life and tapers in adulthood. This is exemplified in the primary visual cortex, where brief loss of vision to one eye abrogates cortical responses to inputs from that eye during the critical period, but not in adulthood. The synaptic locus of critical period plasticity and the cell-autonomous synaptic factors timing these periods remain unclear. We here demonstrate that the immunoglobulin protein Synaptic Cell Adhesion Molecule 1 (SynCAM 1/Cadm1) is regulated by visual experience and limits visual cortex plasticity. SynCAM 1 selectively controls the number of excitatory thalamocortical (TC) inputs onto Parvalbumin (PV+) interneurons and loss of SynCAM 1 in turn impairs the maturation of TC-driven feed-forward inhibition. SynCAM 1 acts in cortical PV+ interneurons to perform these functions and its PV+-specific knockdown prevents the age-related plasticity decline. These results identify a synapse type-specific, cell-autonomous mechanism that governs circuit maturation and closes the visual critical period.

scholarly journals The Function of Activity-Regulated Genes in the Nervous System

2009 ◽  
Vol 89 (4) ◽  
pp. 1079-1103 ◽  
Author(s):  
Sven Loebrich ◽  
Elly Nedivi
Keyword(s):  
Transcriptional Control ◽  
Brain Plasticity ◽  
Neuronal Morphology ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Current View ◽  
Control Mechanisms ◽  
Critical Periods ◽  
Cellular Functions ◽  
Dynamic Tuning

The mammalian brain is plastic in the sense that it shows a remarkable capacity for change throughout life. The contribution of neuronal activity to brain plasticity was first recognized in relation to critical periods of development, when manipulating the sensory environment was found to profoundly affect neuronal morphology and receptive field properties. Since then, a growing body of evidence has established that brain plasticity extends beyond development and is an inherent feature of adult brain function, spanning multiple domains, from learning and memory to adaptability of primary sensory maps. Here we discuss evolution of the current view that plasticity of the adult brain derives from dynamic tuning of transcriptional control mechanisms at the neuronal level, in response to external and internal stimuli. We then review the identification of “plasticity genes” regulated by changes in the levels of electrical activity, and how elucidating their cellular functions has revealed the intimate role transcriptional regulation plays in fundamental aspects of synaptic transmission and circuit plasticity that occur in the brain on an every day basis.

scholarly journals Pharmacological and optical activation of TrkB in Parvalbumin interneurons regulate intrinsic states to orchestrate cortical plasticity

2021 ◽  
Author(s):  
Frederike Winkel ◽  
Maria Ryazantseva ◽  
Mathias B. Voigt ◽  
Giuliano Didio ◽  
Antonia Lilja ◽  
...  
Keyword(s):  
Environmental Enrichment ◽  
Pyramidal Neurons ◽  
Cortical Plasticity ◽  
Brain Plasticity ◽  
Antidepressant Treatment ◽  
Ocular Dominance ◽  
Adult Brain ◽  
Postnatal Life ◽  
Critical Periods ◽  
Cortical Networks

AbstractElevated states of brain plasticity typical for critical periods of early postnatal life can be reinstated in the adult brain through interventions, such as antidepressant treatment and environmental enrichment, and induced plasticity may be critical for the antidepressant action. Parvalbumin-positive (PV) interneurons regulate the closure of developmental critical periods and can alternate between high and low plasticity states in response to experience in adulthood. We now show that PV plasticity states and cortical networks are regulated through the activation of TrkB neurotrophin receptors. Visual cortical plasticity induced by fluoxetine, a widely prescribed selective serotonin reuptake inhibitor (SSRI) antidepressant, was lost in mice with reduced expression of TrkB in PV interneurons. Conversely, optogenetic gain-of-function studies revealed that activation of an optically activatable TrkB (optoTrkB) specifically in PV interneurons switches adult cortical networks into a state of elevated plasticity within minutes by decreasing the intrinsic excitability of PV interneurons, recapitulating the effects of fluoxetine. TrkB activation shifted cortical networks towards a low PV configuration, promoting oscillatory synchrony, increased excitatory-inhibitory balance, and ocular dominance plasticity. OptoTrkB activation promotes the phosphorylation of Kv3.1 channels and reduces the expression of Kv3.2 mRNA providing a mechanism for the lower excitability. In addition, decreased expression and puncta of Synaptotagmin2 (Syt2), a presynaptic marker of PV interneurons involved in Ca2+-dependent neurotransmitter release, suggests lower inputs onto pyramidal neurons suppressing feed-forward inhibition. Together, the results provide mechanistic insights into how TrkB activation in PV interneurons orchestrates the activity of cortical networks and mediating antidepressant responses in the adult brain.

Multisensory integration and neuroplasticity in the human cerebral cortex

2013 ◽  
Vol 4 (3) ◽  
Author(s):  
Evangelos Paraskevopoulos ◽  
Sibylle Herholz
Keyword(s):  
Sensory Processing ◽  
Multisensory Processing ◽  
Brain Plasticity ◽  
Structural Connectivity ◽  
Brain Regions ◽  
Human Cerebral Cortex ◽  
Open Questions ◽  
Multisensory Training ◽  
And Training ◽  
Multisensory Processes

AbstractThere is a strong interaction between multisensory processing and the neuroplasticity of the human brain. On one hand, recent research demonstrates that experience and training in various domains modifies how information from the different senses is integrated; and, on the other hand multisensory training paradigms seem to be particularly effective in driving functional and structural plasticity. Multisensory training affects early sensory processing within separate sensory domains, as well as the functional and structural connectivity between uni- and multisensory brain regions. In this review, we discuss the evidence for interactions of multisensory processes and brain plasticity and give an outlook on promising clinical applications and open questions.

scholarly journals An Extracellular Perspective on CNS Maturation: Perineuronal Nets and the Control of Plasticity

2021 ◽  
Vol 22 (5) ◽  
pp. 2434
Author(s):  
Daniela Carulli ◽  
Joost Verhaagen
Keyword(s):  
Critical Period ◽  
Brain Plasticity ◽  
Time Windows ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Postnatal Life ◽  
Perineuronal Nets ◽  
Critical Periods ◽  
Perineuronal Net ◽  
Memory Processes

During restricted time windows of postnatal life, called critical periods, neural circuits are highly plastic and are shaped by environmental stimuli. In several mammalian brain areas, from the cerebral cortex to the hippocampus and amygdala, the closure of the critical period is dependent on the formation of perineuronal nets. Perineuronal nets are a condensed form of an extracellular matrix, which surrounds the soma and proximal dendrites of subsets of neurons, enwrapping synaptic terminals. Experimentally disrupting perineuronal nets in adult animals induces the reactivation of critical period plasticity, pointing to a role of the perineuronal net as a molecular brake on plasticity as the critical period closes. Interestingly, in the adult brain, the expression of perineuronal nets is remarkably dynamic, changing its plasticity-associated conditions, including memory processes. In this review, we aimed to address how perineuronal nets contribute to the maturation of brain circuits and the regulation of adult brain plasticity and memory processes in physiological and pathological conditions.

scholarly journals Reactivation of critical period plasticity in adult auditory cortex through chemogenetic silencing of parvalbumin-positive interneurons

2019 ◽  
Vol 116 (52) ◽  
pp. 26329-26331 ◽  
Author(s):  
J. Miguel Cisneros-Franco ◽  
Étienne de Villers-Sidani
Keyword(s):  
Auditory Cortex ◽  
Sensory Processing ◽  
Cortical Plasticity ◽  
Cell Activity ◽  
Sound Intensity ◽  
Cortical Inhibition ◽  
Critical Periods ◽  
Cellular Mechanisms ◽  
Perineuronal Net ◽  
Early Developmental

Sensory experience during early developmental critical periods (CPs) has profound and long-lasting effects on cortical sensory processing perduring well into adulthood. Although recent evidence has shown that reducing cortical inhibition during adulthood reinstates CP plasticity, the precise cellular mechanisms are not well understood. Here, we show that chemogenetic inactivation of parvalbumin-positive (PV+) interneurons is sufficient to reinstate CP plasticity in the adult auditory cortex. Bidirectional manipulation of PV+cell activity affected neuronal spectral and sound intensity selectivity and, in the case of PV+interneuron inactivation, was mirrored by anatomical changes in PV and associated perineuronal net expression. These findings underscore the importance of sustained PV-mediated inhibitory neurotransmission throughout life and highlight the potential of chemogenetic approaches for harnessing cortical plasticity with the ultimate goal of aiding recovery from brain injury or disease.

scholarly journals Tooth-Matrix Biomarkers to Reconstruct Critical Periods of Brain Plasticity

2017 ◽  
Vol 40 (1) ◽  
pp. 1-3 ◽  
Author(s):  
Hirofumi Morishita ◽  
Manish Arora
Keyword(s):  
Brain Plasticity ◽  
Critical Periods

scholarly journals The cytogenetic influence of physical water indicators on the number of micronuclears in cells of predatory fish species

2020 ◽  
pp. 142-149
Author(s):  
O. Vodianitskyi ◽  
N. Hrynevych ◽  
O. Khomiak ◽  
N. Prysiazhniuk
Keyword(s):  
Embryonic Development ◽  
Genetic Disorders ◽  
Embryonic Cell ◽  
The Body ◽  
Stress Factors ◽  
Predatory Fish ◽  
Threshold Temperature ◽  
Temperature Threshold ◽  
Critical Periods ◽  
Temperature Deviation

During the monitoring of cytological parameters of embryos and fi sh larvae under changing environmental conditions, it was found that the body adapts to the environmental temperature conditions at the cellular level. Threshold temperature is the limit of the resistance of body cells to the action of extreme ambient temperatures. Since this ability is diff erent for diff erent species, their temperature threshold is not the same. It is proved that for each fi sh species there is a certain temperature amplitude, within which their embryonic development is possible. The rate of passage of embryogenesis depends on temperature. Deviation from the optimal temperature and its approach to the “threshold” causes disturbances in the embryogenesis of fi sh, leads to the death of embryos or to the appearance of anomalies in their development. Under the infl uence of a threshold temperature on fertilized eggs, polyploidy of cells is possible. Genetic changes in somatic cells is an integral indicator of homeostasis disturbance. They characterize the pr esence of environmental mutagens and the eff ectiveness of the body's immune response. Normally, most genetic disorders are eliminated. The presence of such disorders is an indicator of stress, which leads to the appearance of abnormal cells and a decrease in the body's immune status. Such abnormalities can be detected at the chromosomal level. It has been proved that critical periods in the embryonic development of fi sh are manifested at the stages of crushing of morula cells and gastrulation in embryos during organogenesis. However, the presence of sensitive periods is not always associated with diff erentiation processes, for example, the onset of cell crushing, the period of embryo exit from the membranes. Key words: predatory fi sh species, temperature regime, metabolism, micronuclear test, embryonic cell, nucleoli, stress factors, abiotic effect.

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