scholarly journals Autism: A “Critical Period” Disorder?

2011 ◽  
Vol 2011 ◽  
pp. 1-17 ◽  
Author(s):  
Jocelyn J. LeBlanc ◽  
Michela Fagiolini
Keyword(s):  
Critical Period ◽  
Molecular Mechanisms ◽  
Neurodevelopmental Disorder ◽  
Repetitive Behaviors ◽  
Postnatal Life ◽  
Critical Periods ◽  
Restricted Interests ◽  
Behavioral Impairments ◽  
And Function ◽  
The Brain

Cortical circuits in the brain are refined by experience during critical periods early in postnatal life. Critical periods are regulated by the balance of excitatory and inhibitory (E/I) neurotransmission in the brain during development. There is now increasing evidence of E/I imbalance in autism, a complex genetic neurodevelopmental disorder diagnosed by abnormal socialization, impaired communication, and repetitive behaviors or restricted interests. The underlying cause is still largely unknown and there is no fully effective treatment or cure. We propose that alteration of the expression and/or timing of critical period circuit refinement in primary sensory brain areas may significantly contribute to autistic phenotypes, including cognitive and behavioral impairments. Dissection of the cellular and molecular mechanisms governing well-established critical periods represents a powerful tool to identify new potential therapeutic targets to restore normal plasticity and function in affected neuronal circuits.

scholarly journals The ex-illiterate brain: The critical period, cognitive reserve and HAROLD model

2009 ◽  
Vol 3 (3) ◽  
pp. 222-227 ◽  
Author(s):  
Maria Vania Silva Nunes ◽  
Alexandre Castro-Caldas ◽  
Dolores Del Rio ◽  
Fernado Maestú ◽  
Tomás Ortiz
Keyword(s):  
Recognition Test ◽  
Cognitive Skills ◽  
Critical Period ◽  
Cognitive Reserve ◽  
Brain Activity ◽  
High Educational Level ◽  
Critical Periods ◽  
Language Recognition ◽  
Regular Time ◽  
The Brain

Abstract The lifelong acquisition of cognitive skills shapes the biology of the brain. However, there are critical periods for the best use of the brain to process the acquired information. Objectives: To discuss the critical period of cognitive acquisition, the concept of cognitive reserve and the HAROLD (Hemispheric Asymmetry Reduction in Older adults) model. Methods: Seven women who learned how to read and to write after the age of 50 (ex-illiterates) and five women with 10 years of regular schooling (controls) were submitted to a language recognition test while brain activity was being recorded using magnetoencephalography. Spoken words were delivered binaurally via two plastic tubs terminating in ear inserts, and recordings were made with a whole head magnetometer consisting of 148 magnetometer coils. Results: Both groups performed similarly on the task of identifying target words. Analysis of the number of sources of activity in the left and right hemispheres revealed significant differences between the two groups, showing that ex-illiterate subjects exhibited less brain functional asymmetry during the language task. Conclusions: These results should be interpreted with caution because the groups were small. However, these findings reinforce the concept that poorly educated subjects tend to use the brain for information processing in a different way to subjects with a high educational level or who were schooled at the regular time. Finally, the recruiting of both hemispheres to tackle the language recognition test occurred to a greater degree in the ex-illiterate group where this can be interpreted as a sign of difficulty performing the task.

scholarly journals Critical periods in amblyopia

2018 ◽  
Vol 35 ◽  
Author(s):  
TAKAO K. HENSCH ◽  
ELIZABETH M. QUINLAN
Keyword(s):  
Visual Cortex ◽  
Critical Period ◽  
Molecular Mechanisms ◽  
Ocular Dominance ◽  
Molecular Genetic ◽  
Monocular Deprivation ◽  
Critical Periods ◽  
Developmental Constraints ◽  
Early Postnatal Development ◽  
Visual Cortical

AbstractThe shift in ocular dominance (OD) of binocular neurons induced by monocular deprivation is the canonical model of synaptic plasticity confined to a postnatal critical period. Developmental constraints on this plasticity not only lend stability to the mature visual cortical circuitry but also impede the ability to recover from amblyopia beyond an early window. Advances with mouse models utilizing the power of molecular, genetic, and imaging tools are beginning to unravel the circuit, cellular, and molecular mechanisms controlling the onset and closure of the critical periods of plasticity in the primary visual cortex (V1). Emerging evidence suggests that mechanisms enabling plasticity in juveniles are not simply lost with age but rather that plasticity is actively constrained by the developmental up-regulation of molecular ‘brakes’. Lifting these brakes enhances plasticity in the adult visual cortex, and can be harnessed to promote recovery from amblyopia. The reactivation of plasticity by experimental manipulations has revised the idea that robust OD plasticity is limited to early postnatal development. Here, we discuss recent insights into the neurobiology of the initiation and termination of critical periods and how our increasingly mechanistic understanding of these processes can be leveraged toward improved clinical treatment of adult amblyopia.

scholarly journals Linking Autism Risk Genes to Disruption of Cortical Development

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2500
Author(s):  
Marta Garcia-Forn ◽  
Andrea Boitnott ◽  
Zeynep Akpinar ◽  
Silvia De Rubeis
Keyword(s):  
Large Scale ◽  
Association Studies ◽  
Neurodevelopmental Disorder ◽  
Cortical Development ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Genome Wide Association Studies ◽  
Restricted Interests ◽  
Risk Genes ◽  
Whole Exome

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder characterized by impairments in social communication and social interaction, and the presence of repetitive behaviors and/or restricted interests. In the past few years, large-scale whole-exome sequencing and genome-wide association studies have made enormous progress in our understanding of the genetic risk architecture of ASD. While showing a complex and heterogeneous landscape, these studies have led to the identification of genetic loci associated with ASD risk. The intersection of genetic and transcriptomic analyses have also begun to shed light on functional convergences between risk genes, with the mid-fetal development of the cerebral cortex emerging as a critical nexus for ASD. In this review, we provide a concise summary of the latest genetic discoveries on ASD. We then discuss the studies in postmortem tissues, stem cell models, and rodent models that implicate recently identified ASD risk genes in cortical development.

scholarly journals Gene Expression Patterns Underlying the Reinstatement of Plasticity in the Adult Visual System

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Ettore Tiraboschi ◽  
Ramon Guirado ◽  
Dario Greco ◽  
Petri Auvinen ◽  
Jose Fernando Maya-Vetencourt ◽  
...  
Keyword(s):  
Gene Expression ◽  
Visual Cortex ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Monocular Deprivation ◽  
Adult Brain ◽  
Gene Expression Patterns ◽  
Postnatal Life ◽  
Critical Periods

The nervous system is highly sensitive to experience during early postnatal life, but this phase of heightened plasticity decreases with age. Recent studies have demonstrated that developmental-like plasticity can be reactivated in the visual cortex of adult animals through environmental or pharmacological manipulations. These findings provide a unique opportunity to study the cellular and molecular mechanisms of adult plasticity. Here we used the monocular deprivation paradigm to investigate large-scale gene expression patterns underlying the reinstatement of plasticity produced by fluoxetine in the adult rat visual cortex. We found changes, confirmed with RT-PCRs, in gene expression in different biological themes, such as chromatin structure remodelling, transcription factors, molecules involved in synaptic plasticity, extracellular matrix, and excitatory and inhibitory neurotransmission. Our findings reveal a key role for several molecules such as the metalloproteases Mmp2 and Mmp9 or the glycoprotein Reelin and open up new insights into the mechanisms underlying the reopening of the critical periods in the adult brain.

Early Defects of GABAergic Synapses in the Brain Stem of a MeCP2 Mouse Model of Rett Syndrome

2008 ◽  
Vol 99 (1) ◽  
pp. 112-121 ◽  
Author(s):  
L. Medrihan ◽  
E. Tantalaki ◽  
G. Aramuni ◽  
V. Sargsyan ◽  
I. Dudanova ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Brain Stem ◽  
Rett Syndrome ◽  
Time Course ◽  
Molecular Mechanisms ◽  
Neurodevelopmental Disorder ◽  
Therapeutic Interventions ◽  
Ventrolateral Medulla ◽  
Diagnostic Tools ◽  
The Brain

Rett syndrome is a neurodevelopmental disorder caused by mutations in the transcriptional repressor methyl-CpG-binding protein 2 (MeCP2) and represents the leading genetic cause for mental retardation in girls. MeCP2-mutant mice have been generated to study the molecular mechanisms of the disease. It was suggested that an imbalance between excitatory and inhibitory neurotransmission is responsible for the behavioral abnormalities, although it remained largely unclear which synaptic components are affected and how cellular impairments relate to the time course of the disease. Here, we report that MeCP2 KO mice present an imbalance between inhibitory and excitatory synaptic transmission in the ventrolateral medulla already at postnatal day 7. Focusing on the inhibitory synaptic transmission we show that GABAergic, but not glycinergic, synaptic transmission is strongly depressed in MeCP2 KO mice. These alterations are presumably due to both decreased presynaptic γ-aminobutyric acid (GABA) release with reduced levels of the vesicular inhibitory transmitter transporter and reduced levels of postsynaptic GABAA-receptor subunits α2 and α4. Our data indicate that in the MeCP2 −/y mice specific synaptic molecules and signaling pathways are impaired in the brain stem during early postnatal development. These observations mandate the search for more refined diagnostic tools and may provide a rationale for the timing of future therapeutic interventions in Rett patients.

scholarly journals Translational animal models of autism and neurodevelopmental disorders

2012 ◽  
Vol 14 (3) ◽  
pp. 293-305 ◽  
Keyword(s):  
Mouse Models ◽  
De Novo ◽  
Single Gene ◽  
Neurodevelopmental Disorder ◽  
Gene Mutations ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Restricted Interests ◽  
Homologous Genes ◽  
Biological Outcomes

Autism is a neurodevelopmental disorder whose diagnosis is based on three behavioral criteria: unusual reciprocal social interactions, deficits in communication, and stereotyped repetitive behaviors with restricted interests. A large number of de novo single gene mutations and chromosomal deletions are associated with autism spectrum disorders. Based on the strong genetic evidence, mice with targeted mutations in homologous genes have been generated as translational research tools. Mouse models of autism have revealed behavioral and biological outcomes of mutations in risk genes. The field is now poised to employ the most robust phenotypes in the most replicable mouse models for preclinical screening of novel therapeutics.

scholarly journals Microglia in the developing retina

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Fenge Li ◽  
Danye Jiang ◽  
Melanie A. Samuel
Keyword(s):  
Molecular Mechanisms ◽  
Neuron Development ◽  
Laminar Organization ◽  
Retina Development ◽  
Retinal Microglia ◽  
Mammalian Retina ◽  
Underlying Mechanisms ◽  
And Function ◽  
Neuron Function ◽  
The Brain

AbstractMicroglia are increasingly shown to be key players in neuron development and synapse connectivity. However, the underlying mechanisms by which microglia regulate neuron function remain poorly understood in part because such analysis is challenging in the brain where neurons and synapses are intermingled and connectivity is only beginning to be mapped. Here, we discuss the features and function of microglia in the ordered mammalian retina where the laminar organization of neurons and synapses facilitates such molecular studies. We discuss microglia origins and consider the evidence for molecularly distinct microglia subpopulations and their potential for differential roles with a particular focus on the early stages of retina development. We then review the models and methods used for the study of these cells and discuss emerging data that link retina microglia to the genesis and survival of particular retina cell subtypes. We also highlight potential roles for microglia in shaping the development and organization of the vasculature and discuss cellular and molecular mechanisms involved in this process. Such insights may help resolve the mechanisms by which retinal microglia impact visual function and help guide studies of related features in brain development and disease.

scholarly journals Pathogenetical and Neurophysiological Features of Patients with Autism Spectrum Disorder: Phenomena and Diagnoses

2019 ◽  
Vol 8 (10) ◽  
pp. 1588
Author(s):  
Yunho Jin ◽  
Jeonghyun Choi ◽  
Seunghoon Lee ◽  
Jong Won Kim ◽  
Yonggeun Hong
Keyword(s):  
Autism Spectrum Disorder ◽  
Neural Development ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Social Deficits ◽  
Restricted Interests ◽  
Neuropsychiatric Comorbidities ◽  
The Brain

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is accompanied by social deficits, repetitive and restricted interests, and altered brain development. The majority of ASD patients suffer not only from ASD itself but also from its neuropsychiatric comorbidities. Alterations in brain structure, synaptic development, and misregulation of neuroinflammation are considered risk factors for ASD and neuropsychiatric comorbidities. Electroencephalography has been developed to quantitatively explore effects of these neuronal changes of the brain in ASD. The pineal neurohormone melatonin is able to contribute to neural development. Also, this hormone has an inflammation-regulatory role and acts as a circadian key regulator to normalize sleep. These functions of melatonin may play crucial roles in the alleviation of ASD and its neuropsychiatric comorbidities. In this context, this article focuses on the presumable role of melatonin and suggests that this hormone could be a therapeutic agent for ASD and its related neuropsychiatric disorders.

scholarly journals Regulation of Reelin functions by specific proteolytic processing in the brain

2021 ◽  
Author(s):  
Mitsuharu Hattori ◽  
Takao Kohno
Keyword(s):  
Synaptic Plasticity ◽  
Neuronal Migration ◽  
Molecular Mechanisms ◽  
Proteolytic Processing ◽  
Postnatal Brain ◽  
Dendrite Development ◽  
Mature Brain ◽  
Neuropsychiatric Diseases ◽  
And Function ◽  
The Brain

Abstract The secreted glycoprotein Reelin plays important roles in both brain development and function. During development, Reelin regulates neuronal migration and dendrite development. In the mature brain, the glycoprotein is involved in synaptogenesis and synaptic plasticity. It has been suggested that Reelin loss or decreased function contributes to the onset and/or deterioration of neuropsychiatric diseases, including schizophrenia and Alzheimer’s disease. While the molecular mechanisms underpinning Reelin function remain unclear, recent studies have suggested that the specific proteolytic cleavage of Reelin may play central roles in the embryonic and postnatal brain. In this review, we focus on Reelin proteolytic processing and review its potential physiological roles.

scholarly journals Brain Structural Covariance Network in Asperger’s Syndrome Differs From Other Types of Autism and Healthy Controls

2021 ◽  
Author(s):  
Farnaz Faridi ◽  
◽  
Afrooz Seyedebrahimi ◽  
Reza Khosrowabadi ◽  
◽  
...  
Keyword(s):  
Asperger's Syndrome ◽  
Asperger’S Syndrome ◽  
Neurodevelopmental Disorder ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Healthy Controls ◽  
Structural Differentiation ◽  
Structural Covariance ◽  
Behavioral Impairments ◽  
The Brain

Autism is a heterogeneous neurodevelopmental disorder associated with social, cognitive and behavioral impairments. These impairments are often reported along with alteration of the brain structure such as abnormal changes in the grey matter (GM) density. However, it is not yet clear whether these changes could be used to differentiate various subtypes of autism spectrum disorder (ASD). In this study, we compared the regional changes of GM density in ASD, Asperger's Syndrome (AS) individuals and a group of healthy controls (HC). In addition to regional changes itself, the amount of GM density changes in one region as compared to other brain regions was also calculated. We hypothesized that this structural covariance network could differentiate the AS individuals from the ASD and HC groups. Therefore, statistical analysis was performed on the MRI data of 70 male subjects including 26 ASD (age= 14-50, IQ= 92-132), 16 AS (age=7-58, IQ=93-133) and 28 HC (age=9-39, IQ=95-144). Results of one-way ANOVA on the GM density of 116 anatomically separated regions showed significant differences among the groups. The pattern of structural covariance network indicated that covariation of GM density between the brain regions is decreased in ASD. This attenuated structural differentiation could be considered as a reason for less efficient segregation and integration of information in the brain that could lead to cognitive dysfunctions in autism. We hope these findings could improve our understanding about the pathobiology of autism and may pave the way towards a more effective intervention paradigm.

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