Document Type

Article

Publication Date

4-28-2018

Publication Title

Frontiers in Molecular Neuroscience

Volume

11

First page number:

1

Last page number:

23

Abstract

The term neurodevelopmental disorder (NDD) is an umbrella term used to group together a heterogeneous class of disorders characterized by disruption in cognition, emotion, and behavior, early in the developmental timescale. These disorders are heterogeneous, yet they share common behavioral symptomatology as well as overlapping genetic contributors, including proteins involved in the formation, specialization, and function of synaptic connections. Advances may arise from bridging the current knowledge on synapse related factors indicated from both human studies in NDD populations, and in animal models. Mounting evidence has shown a link to inhibitory synapse formation, specialization, and function among Autism, Angelman, Rett and Dravet syndromes. Inhibitory signaling is diverse, with numerous subtypes of inhibitory interneurons, phasic and tonic modes of inhibition, and the molecular and subcellular diversity of GABAA receptors. We discuss common ribs of inhibitory synapse dysfunction in the umbrella of NDD, highlighting alterations in the developmental switch to inhibitory GABA, dysregulation of neuronal activity patterns by parvalbumin-positive interneurons, and impaired tonic inhibition. Increasing our basic understanding of inhibitory synapses, and their role in NDDs is likely to produce significant therapeutic advances in behavioral symptom alleviation for interrelated NDDs. Highlights • Human studies and animal models need to be bridged in neurodevelopmental disorders • Inhibitory signaling emerges as a common contributor to neurodevelopmental disorders • Inhibitory signaling is diverse in mode, source, and target • Systematic evaluation of inhibitory diversity is lacking in neurodevelopment • Understanding of inhibitory signaling diversity will advance therapeutic strategies

Keywords

Neurodevelopment; GABA A receptor; Autism spectrum disorders; Rett Syndrome (RTT); Angelman Syndrome; Dravet Syndrome; Seizures; Phasic and tonic inhibition

Disciplines

Medicine and Health Sciences | Neurosciences

File Format

application/pdf

File Size

1.183 Kb

Language

English

Publisher Citation

Ali Rodriguez R, Joya C and Hines RM (2018) Common Ribs of Inhibitory Synaptic Dysfunction in the Umbrella of Neurodevelopmental Disorders. Front. Mol. Neurosci. 11:132. doi: 10.3389/fnmol.2018.00132

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