scholarly journals A Songbird Animal Model for Dissecting the Genetic Bases of Autism Spectrum Disorder

2012 ◽  
Vol 33 (5) ◽  
pp. 241-249 ◽  
Author(s):  
S. Carmen Panaitof
Keyword(s):  
Autism Spectrum Disorder ◽  
Animal Model ◽  
Language Development ◽  
Critical Role ◽  
Vocal Learning ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Laboratory Animals ◽  
Human Language ◽  
Genetic Bases

The neural and genetic bases of human language development and associated neurodevelopmental disorders, including autism spectrum disorder (ASD), in which language impairment represents a core deficit, are poorly understood. Given that no single animal model can fully capture the behavioral and genetic complexity of ASD, work in songbird, an experimentally tractable animal model of vocal learning, can complement the valuable tool of rodent genetic models and contribute important insights to our understanding of the communication deficits observed in ASD. Like humans, but unlike traditional laboratory animals such as rodents or non-human primates, songbirds exhibit the capacity of vocal learning, a key subcomponent of language. Human speech and birdsong reveal important parallels, highlighting similar developmental critical periods, a homologous cortico-basal ganglia-thalamic circuitry, and a critical role for social influences in the learning of vocalizations. Here I highlight recent advances in using the songbird model to probe the cellular and molecular mechanisms underlying the formation and function of neural circuitry for birdsong and, by analogy, human language, with the ultimate goal of identifying any shared or human unique biological pathways underscoring language development and its disruption in ASD.

Development of Neural Structure and Function in Autism Spectrum Disorder: Potential Implications for Learning Language

2020 ◽  
Vol 29 (4) ◽  
pp. 1783-1797
Author(s):  
Kelly L. Coburn ◽  
Diane L. Williams
Keyword(s):  
Autism Spectrum Disorder ◽  
Language Development ◽  
Diffusion Tensor ◽  
Autism Spectrum ◽  
Language Intervention ◽  
Spectrum Disorder ◽  
Autistic Children ◽  
Neural Structure ◽  
Complex Information ◽  
And Function

Purpose Neurodevelopmental processes that begin during gestation and continue throughout childhood typically support language development. Understanding these processes can help us to understand the disruptions to language that occur in neurodevelopmental conditions, such as autism spectrum disorder (ASD). Method For this tutorial, we conducted a focused literature review on typical postnatal brain development and structural and functional magnetic resonance imaging, diffusion tensor imaging, magnetoencephalography, and electroencephalography studies of the neurodevelopmental differences that occur in ASD. We then integrated this knowledge with the literature on evidence-based speech-language intervention practices for autistic children. Results In ASD, structural differences include altered patterns of cortical growth and myelination. Functional differences occur at all brain levels, from lateralization of cortical functions to the rhythmic activations of single neurons. Neuronal oscillations, in particular, could help explain disrupted language development by elucidating the timing differences that contribute to altered functional connectivity, complex information processing, and speech parsing. Findings related to implicit statistical learning, explicit task learning, multisensory integration, and reinforcement in ASD are also discussed. Conclusions Consideration of the neural differences in autistic children provides additional scientific support for current recommended language intervention practices. Recommendations consistent with these neurological findings include the use of short, simple utterances; repetition of syntactic structures using varied vocabulary; pause time; visual supports; and individualized sensory modifications.

scholarly journals Alterations of the endocannabinoid system and its therapeutic potential in autism spectrum disorder

Open Biology ◽  
2021 ◽  
Vol 11 (2) ◽  
Author(s):  
Mingyang Zou ◽  
Yu Liu ◽  
Shu Xie ◽  
Luxi Wang ◽  
Dexin Li ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Animal Model ◽  
Social Preference ◽  
Therapeutic Potential ◽  
Hydrolytic Enzyme ◽  
Endocannabinoid System ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Autistic Children ◽  
Novel Approach

Autism spectrum disorder (ASD) is a group of developmental disabilities, the aetiology of which remains elusive. The endocannabinoid (eCB) system modulates neurotransmission and neuronal plasticity. Evidence points to the involvement of this neuromodulatory system in the pathophysiology of ASD. We investigated whether there is a disruption to the eCB system in ASD and whether pharmacological modulation of the eCB system might offer therapeutic potential. We examined three major components of the eCB system—endogenous cannabinoids, their receptors and associated enzymes—in ASD children as well as in the valproic acid (VPA) induced animal model in autism. Furthermore, we specifically increased 2-arachidonoylglycerol (2-AG) levels by administering JZL184, a selective inhibitor of monoacylglycerol lipase which is the hydrolytic enzyme for 2-AG, to examine ASD-like behaviours in VPA-induced rats. Results showed that autistic children and VPA-induced rats exhibited reduced eCB content, increased degradation of enzymes and upregulation of CBRs. We found that repetitive and stereotypical behaviours, hyperactivity, sociability, social preference and cognitive functioning improved after acute and chronic JZL184 treatment. The major efficacy of JZL184 was observed after administration of a dosage regimen of 3 mg kg −1 , which affected both the eCB system and ASD-like behaviours. In conclusion, a reduced eCB signalling was observed in autistic children and in the ASD animal model, and boosting 2-AG could ameliorate ASD-like phenotypes in animals. Collectively, the results suggested a novel approach to ASD treatment.

scholarly journals The role of caregiver speech in supporting language development in infants and toddlers with autism spectrum disorder

2020 ◽  
Vol 32 (4) ◽  
pp. 1230-1239 ◽  
Author(s):  
Meghan R. Swanson
Keyword(s):  
Autism Spectrum Disorder ◽  
Language Development ◽  
Best Practice ◽  
Intervention Studies ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Language Research ◽  
Language Data

AbstractParents play an essential role in supporting child development by providing a safe home, proper nutrition, and rich educational opportunities. In this article we focus on the role of caregiver speech in supporting development of young children with autism spectrum disorder (ASD). We review studies from typically developing children and children with autism showing that rich and responsive caregiver speech supports language development. Autism intervention studies that target caregiver speech are reviewed as are recent scientific advances from studies of typical development. The strengths and weakness of different techniques for collecting language data from caregivers and children are reviewed, and natural language samples are recommended as best practice for language research in autism. We conclude that caregivers play a powerful role in shaping their children's development and encourage researchers to adapt parent-mediated intervention studies to acknowledge individual differences in parents by using a personalized medicine approach.

scholarly journals Use of Longitudinal EEG Measures in Estimating Language Development in Infants With and Without Familial Risk for Autism Spectrum Disorder

2020 ◽  
Vol 1 (1) ◽  
pp. 33-53 ◽  
Author(s):  
Carol L. Wilkinson ◽  
Laurel J. Gabard-Durnam ◽  
Kush Kapur ◽  
Helen Tager-Flusberg ◽  
April R. Levin ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
High Risk ◽  
Language Development ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Risk Status ◽  
Prospective Longitudinal Study ◽  
Frequency Bands ◽  
Eeg Power ◽  
Prospective Longitudinal

Language development in children with autism spectrum disorder (ASD) varies greatly among affected individuals and is a strong predictor of later outcomes. Younger siblings of children with ASD have increased risk of ASD, but also language delay. Identifying neural markers of language outcomes in infant siblings could facilitate earlier intervention and improved outcomes. This study aimed to determine whether electroencephalography (EEG) measures from the first 2 years of life can explain heterogeneity in language development in children at low and high risk for ASD, and whether associations between EEG measures and language development are different depending on ASD risk status or later ASD diagnosis. In this prospective longitudinal study, EEG measures collected between 3 and 24 months were used in a multivariate linear regression model to estimate participants’ 24-month language development. Individual baseline longitudinal EEG measures included (1) the slope of EEG power across 3 to 12 months or 3 to 24 months of life for six canonical frequency bands, (2) the estimated EEG power at 6 months of age for the same frequency bands, and (3) terms representing the interaction between ASD risk status and EEG power measures. Modeled 24-month language scores using EEG data from either the first 2 years (Pearson p = 0.70, 95% CI [0.595, 0.783], p = 1 × 10−18) or the first year of life (Pearson p = 0.66, 95% CI [0.540, 0.761], p = 2.5 × 10−14) were highly correlated with observed scores. All models included significant interaction effects of risk on EEG measures, suggesting that EEG-language associations are different depending on risk status, and that different brain mechanisms affect language development in low- versus high-risk infants.

scholarly journals What We Have Learned about Autism Spectrum Disorder from Valproic Acid

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Taylor Chomiak ◽  
Nathanael Turner ◽  
Bin Hu
Keyword(s):  
Autism Spectrum Disorder ◽  
Valproic Acid ◽  
Animal Model ◽  
Neurodevelopmental Disorders ◽  
Significant Risk ◽  
Autism Spectrum ◽  
Research Literature ◽  
Spectrum Disorder ◽  
Epidemiological Evidence ◽  
Growing Body

Two recent epidemiological investigations in children exposed to valproic acid (VPA) treatment in utero have reported a significant risk associated with neurodevelopmental disorders and autism spectrum disorder (ASD) in particular. Parallel to this work, there is a growing body of animal research literature using VPA as an animal model of ASD. In this focused review we first summarize the epidemiological evidence linking VPA to ASD and then comment on two important neurobiological findings linking VPA to ASD clinicopathology, namely, accelerated or early brain overgrowth and hyperexcitable networks. Improving our understanding of how the drug VPA can alter early development of neurological systems will ultimately improve our understanding of ASD.

scholarly journals The Untouchable Ventral Nucleus of the Trapezoid Body: Preservation of a Nucleus in an Animal Model of Autism Spectrum Disorder

2021 ◽  
Vol 15 ◽  
Author(s):  
Yusra Mansour ◽  
Randy J. Kulesza
Keyword(s):  
Autism Spectrum Disorder ◽  
Animal Model ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Spectrum Disorder ◽  
Superior Olivary Complex ◽  
Medial Geniculate ◽  
Ventral Nucleus ◽  
Descending Projections ◽  
Trapezoid Body

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by repetitive behaviors, poor social skills, and difficulties with communication and hearing. The hearing deficits in ASD range from deafness to extreme sensitivity to routine environmental sounds. Previous research from our lab has shown drastic hypoplasia in the superior olivary complex (SOC) in both human cases of ASD and in an animal model of autism. However, in our study of the human SOC, we failed to find any changes in the total number of neurons in the ventral nucleus of the trapezoid body (VNTB) or any changes in cell body size or shape. Similarly, in animals prenatally exposed to the antiepileptic valproic acid (VPA), we failed to find any changes in the total number, size or shape of VNTB neurons. Based on these findings, we hypothesized that the neurotransmitter profiles, ascending and descending axonal projections of the VNTB are also preserved in these neurodevelopmental conditions. We investigated this hypothesis using a combination of immunohistochemistry and retrograde tract tracing. We found no difference between control and VPA-exposed animals in the number of VNTB neurons immunoreactive for choline acetyltransferase (ChAT). Additionally, we investigated the ascending projections from the VNTB to both the central nucleus of the inferior colliculus (CNIC) and medial geniculate (MG) and descending projections to the cochlea. Our results indicate no significant differences in the ascending and descending projections from the VNTB between control and VPA-exposed animals despite drastic changes in these projections from surrounding nuclei. These findings provide evidence that certain neuronal populations and circuits may be protected against the effects of neurodevelopmental disorders.

scholarly journals Referential expressions in monolingual and bilingual children with and without Autism Spectrum Disorder (ASD): A study of informativeness and definiteness

2021 ◽  
pp. 1-30
Author(s):  
Natalia MEIR ◽  
Rama NOVOGRODSKY
Keyword(s):  
Autism Spectrum Disorder ◽  
Language Development ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Bilingual Children ◽  
Children With Asd ◽  
Referential Use ◽  
Hebrew Language ◽  
Referential Expressions ◽  
Language Universal

Abstract The current study evaluated the separate and combined effects of bilingualism and Autism Spectrum Disorder (ASD) on informativeness and definiteness marking of referential expressions. Hebrew-speaking monolingual children (21 with ASD and 28 with typical language development) and Russian–Hebrew-speaking bilingual children (13 with ASD and 30 with typical language development) aged 4–9 years participated. Informativeness, indexed by referential contrasts, was affected by ASD, but not by bilingualism. Definiteness use was non-target-like in children with ASD and in bilingual children, and it was mainly predicted by children’s morpho-syntactic abilities in Hebrew. Language-universal and language-specific properties of referential use are discussed.

scholarly journals Neuroligin-3: A Circuit-Specific Synapse Organizer That Shapes Normal Function and Autism Spectrum Disorder-Associated Dysfunction

2021 ◽  
Vol 14 ◽  
Author(s):  
Motokazu Uchigashima ◽  
Amy Cheung ◽  
Kensuke Futai
Keyword(s):  
Autism Spectrum Disorder ◽  
Molecular Mechanism ◽  
Strong Association ◽  
Critical Role ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Synaptic Signaling ◽  
Syndromic Asd ◽  
Chemical Synapses ◽  
And Function

Chemical synapses provide a vital foundation for neuron-neuron communication and overall brain function. By tethering closely apposed molecular machinery for presynaptic neurotransmitter release and postsynaptic signal transduction, circuit- and context- specific synaptic properties can drive neuronal computations for animal behavior. Trans-synaptic signaling via synaptic cell adhesion molecules (CAMs) serves as a promising mechanism to generate the molecular diversity of chemical synapses. Neuroligins (Nlgns) were discovered as postsynaptic CAMs that can bind to presynaptic CAMs like Neurexins (Nrxns) at the synaptic cleft. Among the four (Nlgn1-4) or five (Nlgn1-3, Nlgn4X, and Nlgn4Y) isoforms in rodents or humans, respectively, Nlgn3 has a heterogeneous expression and function at particular subsets of chemical synapses and strong association with non-syndromic autism spectrum disorder (ASD). Several lines of evidence have suggested that the unique expression and function of Nlgn3 protein underlie circuit-specific dysfunction characteristic of non-syndromic ASD caused by the disruption of Nlgn3 gene. Furthermore, recent studies have uncovered the molecular mechanism underlying input cell-dependent expression of Nlgn3 protein at hippocampal inhibitory synapses, in which trans-synaptic signaling of specific alternatively spliced isoforms of Nlgn3 and Nrxn plays a critical role. In this review article, we overview the molecular, anatomical, and physiological knowledge about Nlgn3, focusing on the circuit-specific function of mammalian Nlgn3 and its underlying molecular mechanism. This will provide not only new insight into specific Nlgn3-mediated trans-synaptic interactions as molecular codes for synapse specification but also a better understanding of the pathophysiological basis for non-syndromic ASD associated with functional impairment in Nlgn3 gene.

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