Thalamic Control of Cognition and Social Behavior Via Regulation of Gamma-Aminobutyric Acidergic Signaling and Excitation/Inhibition Balance in the Medial Prefrontal Cortex

Biological Psychiatry, Journal Year: 2017, Volume and Issue: 83(8), P. 657 - 669

Published: Dec. 8, 2017

Language: Английский

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Autistic Traits and Abnormal Sensory Experiences in Adults

Journal of Autism and Developmental Disorders, Journal Year: 2013, Volume and Issue: 44(6), P. 1461 - 1469

Published: Dec. 4, 2013

Sensory processing abnormalities are common in autism spectrum disorders (ASD), and now form part of the Diagnostic Statistical Manual 5th Edition (DSM-5) diagnostic criteria, but it is unclear whether they characterize ‘broader phenotype’ disorder. We recruited adults (n = 772) with without an ASD administered Autism Quotient (AQ) along Adult/Adolescent Profile (AASP), Cardiff Anomalous Perceptions Scale (CAPS), Glasgow Questionnaire (GSQ), all questionnaire measures abnormal sensory responsivity. traits were significantly correlated scores on three scales (AQ/GSQ r 0.478; AQ/AASP 0.344; AQ/CAPS 0.333; p < 0.001). This relationship was linear across whole range AQ true both those with, without, diagnosis. It survived correction for anxiety trait scores, other potential confounds such as mental illness migraine.

Language: Английский

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The basolateral amygdala γ‐aminobutyric acidergic system in health and disease

Journal of Neuroscience Research, Journal Year: 2015, Volume and Issue: 94(6), P. 548 - 567

Published: Nov. 19, 2015

The brain comprises an excitatory/inhibitory neuronal network that maintains a finely tuned balance of activity critical for normal functioning. Excitatory in the basolateral amygdala (BLA), region plays central role emotion and motivational processing, is tightly regulated by relatively small population γ‐aminobutyric acid (GABA) inhibitory neurons. Disruption GABAergic inhibition BLA can occur when there loss local interneurons, alteration GABA A receptor activation, or dysregulation mechanisms modulate inhibition. Disruptions control emerge during development, aging populations, after trauma, ultimately resulting hyperexcitability. hyperexcitability manifests behaviorally as increase anxiety, emotional dysregulation, development seizure activity. This Review discusses anatomy, physiology system circuits inhibition, including dopaminergic, serotonergic, noradrenergic, cholinergic systems. We highlight how alterations various neurotransmitter receptors, acid‐sensing ion channel 1a, cannabinoid 1, glutamate subtypes, expressed on transmission defects these systems affect tonus within BLA. Finally, we discuss neurodevelopmental (autism/fragile X syndrome) neurodegenerative (Alzheimer's disease) diseases epilepsy, traumatic injury. more complete understanding intrinsic circuit imbalances contribute to excessive excitability will guide novel therapeutic approaches neuropsychiatric diseases. © 2015 Wiley Periodicals, Inc.

Language: Английский

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Rare exonic deletions implicate the synaptic organizer Gephyrin (GPHN) in risk for autism, schizophrenia and seizures

Human Molecular Genetics, Journal Year: 2013, Volume and Issue: 22(10), P. 2055 - 2066

Published: Feb. 7, 2013

The GPHN gene codes for gephyrin, a key scaffolding protein in the neuronal postsynaptic membrane, responsible clustering and localization of glycine GABA receptors at inhibitory synapses. Gephyrin has well-established functional links with several synaptic proteins that have been implicated genetic risk neurodevelopmental disorders such as autism spectrum disorder (ASD), schizophrenia epilepsy including neuroligins (NLGN2, NLGN4), neurexins (NRXN1, NRXN2, NRXN3) collybistin (ARHGEF9). Moreover, temporal lobe linked to abnormally spliced mRNA lacking exons encoding G-domain gephyrin protein, potentially arising due cellular stress associated epileptogenesis temperature alkalosis. Here, we present clinical genomic characterization six unrelated subjects, range diagnoses ASD, or seizures, who possess rare de novo inherited hemizygous microdeletions overlapping chromosome 14q23.3. region common overlap across deletions encompasses 3–5, corresponding protein. These findings, together previous reports homozygous mutations connection autosomal recessive molybdenum cofactor deficiency, will aid interpretation mutation spectrum. Our data also add accumulating evidence implicating products molecular factors underlying etiologies diverse conditions.

Language: Английский

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Intrinsic excitation-inhibition imbalance affects medial prefrontal cortex differently in autistic men versus women

eLife, Journal Year: 2020, Volume and Issue: 9

Published: Aug. 4, 2020

Excitation-inhibition (E:I) imbalance is theorized as an important pathophysiological mechanism in autism. Autism affects males more frequently than females and sex-related mechanisms (e.g., X-linked genes, androgen hormones) can influence E:I balance. This suggests that may affect autism differently versus females. With a combination of in-silico modeling in-vivo chemogenetic manipulations mice, we first show time-series metric estimated from fMRI BOLD signal, the Hurst exponent (H), be index for underlying change synaptic ratio. In find H reduced, indicating increased excitation, medial prefrontal cortex (MPFC) autistic but not Increasingly intact MPFC also associated with heightened ability to behaviorally camouflage social-communicative difficulties, only work ratio differently.

Language: Английский

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