Advancing the understanding of autism disease mechanisms through genetics

Nature Medicine, Год журнала: 2016, Номер 22(4), С. 345 - 361

Опубликована: Апрель 1, 2016

Язык: Английский

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Excitation-inhibition balance as a framework for investigating mechanisms in neuropsychiatric disorders

Molecular Psychiatry, Год журнала: 2019, Номер 24(9), С. 1248 - 1257

Опубликована: Май 14, 2019

Язык: Английский

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Unexpected role of interferon-γ in regulating neuronal connectivity and social behaviour

Nature, Год журнала: 2016, Номер 535(7612), С. 425 - 429

Опубликована: Июль 1, 2016

Язык: Английский

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PV Interneurons: Critical Regulators of E/I Balance for Prefrontal Cortex-Dependent Behavior and Psychiatric Disorders

Frontiers in Neural Circuits, Год журнала: 2018, Номер 12

Опубликована: Май 16, 2018

Elucidating the prefrontal cortical microcircuit has been challenging, given its role in multiple complex behaviors, including working memory, cognitive flexibility, attention, social interaction, and emotional regulation. Additionally, previous methodological limitations made it difficult to parse out contribution of certain neuronal subpopulations refining representations. However, growing evidence supports a fundamental fast-spiking parvalbumin (PV) GABAergic interneurons regulating pyramidal neuron activity drive appropriate behavioral responses. Further, their function is heavily diminished PFC numerous psychiatric diseases, schizophrenia autism. Previous research demonstrated importance optimal balance excitation inhibition (E/I) circuits maintaining efficiency information processing. Although we are still unraveling mechanisms representation cortex (PFC), E/I seems be crucial, as pharmacological, chemogenetic, optogenetic approaches for disrupting induce impairments range PFC-dependent behaviors. In this review, will explore two key hypotheses. First, PV powerful regulators PFC, help optimize processing supramodal PFC. Second, diminishing sufficient generate an elaborate symptom sequelae corresponding those observed diseases. Then, using framework, speculate on whether circuitry could represent platform development therapeutic interventions disorders function.

Язык: Английский

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Excitation/Inhibition Imbalance in Animal Models of Autism Spectrum Disorders

Biological Psychiatry, Год журнала: 2016, Номер 81(10), С. 838 - 847

Опубликована: Май 22, 2016

Imbalances between excitation and inhibition in synaptic transmission neural circuits have been implicated autism spectrum disorders. Excitation imbalances are frequently observed animal models of disorders, their correction normalizes key autistic-like phenotypes these animals. These results suggest that may contribute to the development maintenance disorders represent an important therapeutic target.

Язык: Английский

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Cannabidiol attenuates seizures and social deficits in a mouse model of Dravet syndrome

Proceedings of the National Academy of Sciences, Год журнала: 2017, Номер 114(42), С. 11229 - 11234

Опубликована: Окт. 2, 2017

Worldwide medicinal use of cannabis is rapidly escalating, despite limited evidence its efficacy from preclinical and clinical studies. Here we show that cannabidiol (CBD) effectively reduced seizures autistic-like social deficits in a well-validated mouse genetic model Dravet syndrome (DS), severe childhood epilepsy disorder caused by loss-of-function mutations the brain voltage-gated sodium channel NaV1.1. The duration severity thermally induced frequency spontaneous were substantially decreased. Treatment with lower doses CBD also improved interaction DS mice. Phenotypic rescue was associated restoration excitability inhibitory interneurons hippocampal dentate gyrus, an important area for seizure propagation. Reduced granule neurons response to strong depolarizing stimuli observed. beneficial effects on neurotransmission mimicked occluded antagonist GPR55, suggesting therapeutic are mediated through this lipid-activated G protein-coupled receptor. Our results provide critical supporting treatment behaviors linked CBD. We introduce antagonism GPR55 as potential approach illustrating study provides essential needed build sound scientific basis increased

Язык: Английский

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The Default Mode Network in Autism

Biological Psychiatry Cognitive Neuroscience and Neuroimaging, Год журнала: 2017, Номер 2(6), С. 476 - 486

Опубликована: Апрель 22, 2017

Язык: Английский

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Sensory Integration in Mouse Insular Cortex Reflects GABA Circuit Maturation

Neuron, Год журнала: 2014, Номер 83(4), С. 894 - 905

Опубликована: Июль 31, 2014

Язык: Английский

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Reversing behavioural abnormalities in mice exposed to maternal inflammation

Nature, Год журнала: 2017, Номер 549(7673), С. 482 - 487

Опубликована: Сен. 12, 2017

Язык: Английский

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GABAergic Signaling as Therapeutic Target for Autism Spectrum Disorders

Frontiers in Pediatrics, Год журнала: 2014, Номер 2

Опубликована: Июль 8, 2014

γ-Aminobutyric acid (GABA), the main inhibitory neurotransmitter in adult brain, early postnatal life exerts a depolarizing and excitatory action. This depends on accumulation of chloride inside cell via cation-chloride importer NKCC1, being expression exporter KCC2 very low at birth. The developmentally regulated results extrusion with age shift GABA from to hyperpolarizing direction. action leads intracellular calcium rise through voltage-dependent channels and/or N-methyl-d-aspartate receptors. GABA-mediated signals regulate variety developmental processes proliferation migration, differentiation, synapse maturation, neuronal wiring. Therefore, it is not surprising that some forms neuro-developmental disorders such as autism spectrum (ASDs) are associated alterations GABAergic signaling impairment excitatory/inhibitory balance selective circuits. In this review, we will discuss how changes GABAA-mediated neurotransmission affect several ASDs including Fragile X, Angelman, Rett syndromes. Then, describe various animal models dysfunctions, highlighting their behavioral deficits possibility rescue them by targeting components synapse. particular, cases, reverting polarity responses direction diuretic bumetanide, blocker may have beneficial effects ASDs, thus opening new therapeutic perspectives for treatment these devastating disorders.

Язык: Английский

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