scholarly journals Registry of Compartmental Ephrin-B3 Guidance Patterns With Respect to Emerging Multimodal Midbrain Maps

2021 ◽  
Vol 15 ◽  
Author(s):  
Jeremiah P. C. Stinson ◽  
Cooper A. Brett ◽  
Julianne B. Carroll ◽  
Mark L. Gabriele
Keyword(s):  
Expression Patterns ◽  
Autism Spectrum ◽  
Postnatal Period ◽  
Acid Decarboxylase ◽  
Signaling Mechanisms ◽  
Sensory Maps ◽  
Spectrum Disorders ◽  
Multiple Levels ◽  
Modular Domains ◽  
Shell Region

Guidance errors and unrefined neural map configurations appear linked to certain neurodevelopmental conditions, including autism spectrum disorders. Deficits in specific multisensory tasks that require midbrain processing are highly predictive of cognitive and behavioral phenotypes associated with such syndromes. The lateral cortex of the inferior colliculus (LCIC) is a shell region of the mesencephalon that integrates converging information from multiple levels and modalities. Mature LCIC sensory maps are discretely-organized, mimicking its compartmental micro-organization. Intermittent modular domains receive patchy somatosensory connections, while inputs of auditory origin terminate in the encompassing extramodular matrix.Eph-ephrin signaling mechanisms instruct comparable topographic arrangements in a variety of other systems. Whether Eph-ephrin interactions also govern the assembly of LCIC multimodal maps remains unaddressed. Previously, we identified EphA4 and ephrin-B2 as key mediators, with overlapping expression patterns that align with emerging LCIC modules. Here, we implicate another member of this guidance family, ephrin-B3, and quantify its transient expression with respect to neurochemically-defined LCIC compartments. Multiple-labeling studies in GAD67-GFP knock-in mice reveal extramodular ephrin-B3 expression, complementary to that of EphA4 and ephrin-B2. This distinctive pattern sharpens over the early postnatal period (birth to P8), prior to ephrin-B3 downregulation once multimodal LCIC inputs are largely segregated (P12). Channel-specific sampling of LCIC ROIs show ephrin-B3 signal periodicities that are out-of-phase with glutamic acid decarboxylase (GAD;modular marker) signal fluctuations, and match calretinin (CR) waveforms (matrix marker). Taken together, the guidance mosaic registry with emerging LCIC compartments and its interfacing afferent streams suggest a prominent role for Eph-ephrins in ordering behaviorally significant multisensory midbrain networks.

scholarly journals Effects of Mutations in TSC Genes on Neurodevelopment and Synaptic Transmission

2021 ◽  
Vol 22 (14) ◽  
pp. 7273
Author(s):  
Davide Bassetti ◽  
Heiko J. Luhmann ◽  
Sergei Kirischuk
Keyword(s):  
Epileptic Seizures ◽  
Autism Spectrum ◽  
Postnatal Period ◽  
Neuronal Function ◽  
Structural Abnormalities ◽  
Neurological Phenotype ◽  
Spectrum Disorders ◽  
Intellectual Deficits ◽  
Cellular Types ◽  
Review Current

Mutations in TSC1 or TSC2 genes are linked to alterations in neuronal function which ultimately lead to the development of a complex neurological phenotype. Here we review current research on the effects that reduction in TSC1 or TSC2 can produce on the developing neural network. A crucial feature of the disease pathophysiology appears to be an early deviation from typical neurodevelopment, in the form of structural abnormalities. Epileptic seizures are one of the primary early manifestation of the disease in the CNS, followed by intellectual deficits and autism spectrum disorders (ASD). Research using mouse models suggests that morphological brain alterations might arise from the interaction of different cellular types, and hyperexcitability in the early postnatal period might be transient. Moreover, the increased excitation-to-inhibition ratio might represent a transient compensatory adjustment to stabilize the developing network rather than a primary factor for the development of ASD symptoms. The inhomogeneous results suggest region-specificity as well as an evolving picture of functional alterations along development. Furthermore, ASD symptoms and epilepsy might originate from different but potentially overlapping mechanisms, which can explain recent observations obtained in patients. Potential treatment is determined not only by the type of medicament, but also by the time point of treatment.

The development of emotion-related neural circuitry in health and psychopathology

2008 ◽  
Vol 20 (4) ◽  
pp. 1231-1250 ◽  
Author(s):  
Christopher S. Monk
Keyword(s):  
Autism Spectrum Disorders ◽  
Brain Function ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Diagnostic Measures ◽  
Different Types ◽  
Spectrum Disorders ◽  
Multiple Levels ◽  
Environmental Events ◽  
Anxiety Depression

AbstractDisturbances in the detection of, response to, and interpretation of emotion are common in many forms of psychopathology. The amygdala, striatum, and structures within the prefrontal cortex are highly involved in mediating these stages of emotion processing, and evidence indicates that these regions show structural and functional alterations in different types of psychopathology, including anxiety, depression, and autism spectrum disorders. However, we do not know how genes and the environment interact to alter development of these brain regions in ways that give rise to emotion-related psychopathology. This review discusses the current understanding of brain regions that are involved in emotional functioning, how they develop, and how they are altered in three forms of psychopathology: anxiety, depression, and autism spectrum disorders. Following this, a framework is described that may facilitate the integration of investigations of genetic variation and brain function with symptom and diagnostic measures. The framework involves three components: (a) a greater emphasis on simultaneously analyzing multiple levels (genes, brain function, behavior, symptoms, and diagnoses); (b) further integration of developmental considerations, including timing of environmental events, adaptations (or maladaptations), and disorder-related trajectories that guide some children toward atypical experiences; and (c) greater cross-talk between animal and human investigations to take advantage of biological measures that cannot be acquired in humans.

scholarly journals Maternal Immunity in Autism Spectrum Disorders: Questions of Causality, Validity, and Specificity

2020 ◽  
Vol 9 (8) ◽  
pp. 2590
Author(s):  
Antonio Ji-Xu ◽  
Angela Vincent
Keyword(s):  
Autism Spectrum Disorders ◽  
Animal Models ◽  
Epidemiological Studies ◽  
Causal Link ◽  
Autism Spectrum ◽  
Clinical Findings ◽  
Postnatal Period ◽  
Maternal Immune Activation ◽  
Spectrum Disorders

Autism spectrum disorders (ASD) are complex neurodevelopmental disorders with unknown heterogeneous aetiologies. Epidemiological studies have found an association between maternal infection and development of ASD in the offspring, and clinical findings reveal a state of immune dysregulation in the pre- and postnatal period of affected subjects. Maternal immune activation (MIA) has been proposed to mediate this association by altering fetal neurodevelopment and leading to autism. Although animal models have supported a causal link between MIA and development of ASD, their validity needs to be explored. Moreover, considering that only a small proportion of affected offspring develop autism, and that MIA has been implicated in related diseases such as schizophrenia, a key unsolved question is how disease specificity and phenotypic outcome are determined. Here, we have integrated preclinical and clinical evidence, including the use of animal models for establishing causality, to explore the role of maternal infections in ASD. A proposed priming/multi-hit model may offer insights into the clinical heterogeneity of ASD, its convergence with related disorders, and therapeutic strategies.

scholarly journals The Brainstem-Informed Autism Framework: Early Life Neurobehavioral Markers

2021 ◽  
Vol 15 ◽  
Author(s):  
Or Burstein ◽  
Ronny Geva
Keyword(s):  
Autism Spectrum Disorders ◽  
Early Identification ◽  
Early Life ◽  
Sensorimotor Integration ◽  
Autism Spectrum ◽  
Autonomic Arousal ◽  
Neurobehavioral Manifestations ◽  
Spectrum Disorders ◽  
Multiple Levels

Autism spectrum disorders (ASD) have long-term implications on functioning at multiple levels. In this perspective, we offer a brainstem-informed autism framework (BIAF) that traces the protracted neurobehavioral manifestations of ASD to early life brainstem dysfunctions. Early life brainstem-mediated markers involving functions of autonomic/arousal regulation, sleep-wake homeostasis, and sensorimotor integration are delineated. Their possible contributions to the early identification of susceptible infants are discussed. We suggest that the BIAF expands our multidimensional understanding of ASD by focusing on the early involvement of brainstem systems. Importantly, we propose an integrated BIAF screener that brings about the prospect of a sensitive and reliable early life diagnostic scheme for weighing the risk for ASD. The BIAF screener could provide clinicians substantial gains in the future and may carve customized interventions long before the current DSM ASD phenotype is manifested using dyadic co-regulation of brainstem-informed autism markers.

scholarly journals Autism Spectrum Disorders: Multiple Routes to, and Multiple Consequences of, Abnormal Synaptic Function and Connectivity

2020 ◽  
pp. 107385842092137 ◽  
Author(s):  
Liam Carroll ◽  
Sven Braeutigam ◽  
John M. Dawes ◽  
Zeljka Krsnik ◽  
Ivica Kostovic ◽  
...  
Keyword(s):  
Autism Spectrum Disorders ◽  
Fragile X ◽  
Autism Spectrum ◽  
Postnatal Period ◽  
Synaptic Function ◽  
Synaptic Dysfunction ◽  
Brain Areas ◽  
Multiple Routes ◽  
Spectrum Disorders ◽  
Phenotypic Specificity

Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental disorders of genetic and environmental etiologies. Some ASD cases are syndromic: associated with clinically defined patterns of somatic abnormalities and a neurobehavioral phenotype (e.g., Fragile X syndrome). Many cases, however, are idiopathic or non-syndromic. Such disorders present themselves during the early postnatal period when language, speech, and personality start to develop. ASDs manifest by deficits in social communication and interaction, restricted and repetitive patterns of behavior across multiple contexts, sensory abnormalities across multiple modalities and comorbidities, such as epilepsy among many others. ASDs are disorders of connectivity, as synaptic dysfunction is common to both syndromic and idiopathic forms. While multiple theories have been proposed, particularly in idiopathic ASDs, none address why certain brain areas (e.g., frontotemporal) appear more vulnerable than others or identify factors that may affect phenotypic specificity. In this hypothesis article, we identify possible routes leading to, and the consequences of, altered connectivity and review the evidence of central and peripheral synaptic dysfunction in ASDs. We postulate that phenotypic specificity could arise from aberrant experience-dependent plasticity mechanisms in frontal brain areas and peripheral sensory networks and propose why the vulnerability of these areas could be part of a model to unify preexisting pathophysiological theories.

scholarly journals The Perturbance of Microbiome and Gut-Brain Axis in Autism Spectrum Disorders

2018 ◽  
Vol 19 (8) ◽  
pp. 2251 ◽  
Author(s):  
Greta Fowlie ◽  
Nicholas Cohen ◽  
Xue Ming
Keyword(s):  
Autism Spectrum Disorder ◽  
Early Childhood ◽  
Autism Spectrum Disorders ◽  
Gut Microbiota ◽  
Autism Spectrum ◽  
Leaky Gut ◽  
Gut Permeability ◽  
Signaling Mechanisms ◽  
Gastrointestinal Problems ◽  
Spectrum Disorders

Gastrointestinal problems have been documented in Autism Spectrum Disorder (ASD). Studies have found that these disturbances may be associated with an altered gut microbiome in ASD. Furthermore, in ASD, these alterations are implicated in increased gut permeability, or “leaky gut”, which allows bacterial metabolites to cross the gut barrier, impacting neurodevelopment during early childhood in susceptible subjects by way of gut-brain axis. In our review, we will discuss the interaction of gut microbiota and brain development in ASD and the signaling mechanisms underlying this interaction. We will also explore the potential for treatment of ASD by targeting the microbiome with probiotics. Finally, this paper will attempt to provide significance to the aggregation of the research in this area of research; providing our interpretations and assessments of future of this field.

Problem behavior in autism spectrum disorders: A paradigmatic self-organized perspective of network structures

2019 ◽  
Vol 42 ◽  
Author(s):  
Lucio Tonello ◽  
Luca Giacobbi ◽  
Alberto Pettenon ◽  
Alessandro Scuotto ◽  
Massimo Cocchi ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Problem Behaviors ◽  
Autism Spectrum ◽  
The Self ◽  
Network Structures ◽  
Self Organized ◽  
Critical Equilibrium ◽  
Self Organized Criticality ◽  
Acute Agitation ◽  
Spectrum Disorders

AbstractAutism spectrum disorder (ASD) subjects can present temporary behaviors of acute agitation and aggressiveness, named problem behaviors. They have been shown to be consistent with the self-organized criticality (SOC), a model wherein occasionally occurring “catastrophic events” are necessary in order to maintain a self-organized “critical equilibrium.” The SOC can represent the psychopathology network structures and additionally suggests that they can be considered as self-organized systems.

Disfluency Characteristics Observed in Young Children With Autism Spectrum Disorders: A Preliminary Report

2010 ◽  
Vol 20 (2) ◽  
pp. 42-50 ◽  
Author(s):  
Laura W. Plexico ◽  
Julie E. Cleary ◽  
Ashlynn McAlpine ◽  
Allison M. Plumb
Keyword(s):  
Autism Spectrum Disorders ◽  
Young Children ◽  
Children With Autism ◽  
Descriptive Study ◽  
Autism Spectrum ◽  
Typically Developing ◽  
Children With Asd ◽  
Young Children With Autism ◽  
Spectrum Disorders ◽  
Developmental Stuttering

This descriptive study evaluates the speech disfluencies of 8 verbal children between 3 and 5 years of age with autism spectrum disorders (ASD). Speech samples were collected for each child during standardized interactions. Percentage and types of disfluencies observed during speech samples are discussed. Although they did not have a clinical diagnosis of stuttering, all of the young children with ASD in this study produced disfluencies. In addition to stuttering-like disfluencies and other typical disfluencies, the children with ASD also produced atypical disfluencies, which usually are not observed in children with typically developing speech or developmental stuttering. (Yairi & Ambrose, 2005).

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