Disrupted inhibitory plasticity and homeostasis in Fragile X syndrome.
Animals
Disease Models, Animal
Excitatory Postsynaptic Potentials
/ physiology
Fragile X Mental Retardation Protein
/ genetics
Fragile X Syndrome
/ genetics
Homeostasis
/ physiology
Inhibitory Postsynaptic Potentials
/ physiology
Mice
Mice, Knockout
Neural Inhibition
/ physiology
Neuronal Plasticity
/ physiology
Pyramidal Cells
/ physiology
Somatosensory Cortex
/ physiopathology
Cortex
Fragile X syndrome
Inhibitory neurotransmission
Interneurons
Plasticity
Journal
Neurobiology of disease
ISSN: 1095-953X
Titre abrégé: Neurobiol Dis
Pays: United States
ID NLM: 9500169
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
11
03
2020
revised:
28
05
2020
accepted:
03
06
2020
pubmed:
9
6
2020
medline:
28
7
2021
entrez:
9
6
2020
Statut:
ppublish
Résumé
Fragile X Syndrome (FXS) is a neurodevelopmental disorder instigated by the absence of a key translation regulating protein, Fragile X Mental Retardation Protein (FMRP). The loss of FMRP in the CNS leads to abnormal synaptic development, disruption of critical periods of plasticity, and an overall deficiency in proper sensory circuit coding leading to hyperexcitable sensory networks. However, little is known about how this hyperexcitable environment affects inhibitory synaptic plasticity. Here, we show that in vivo layer 2/3 of the primary somatosensory cortex of the Fmr1 KO mouse exhibits basal hyperexcitability and an increase in neuronal firing rate suppression during whisker activation. This aligns with our in vitro data that indicate an increase in GABAergic spontaneous activity, a faulty mGluR-mediated inhibitory input and impaired inhibitory plasticity processes. Specifically, we find that mGluR activation sensitivity is overall diminished in the Fmr1 KO mouse leading to both a decreased spontaneous inhibitory postsynaptic input to principal cells and a disrupted form of inhibitory long-term depression (I-LTD). These data suggest an adaptive mechanism that acts to homeostatically counterbalance the cortical hyperexcitability observed in FXS.
Identifiants
pubmed: 32512151
pii: S0969-9961(20)30234-5
doi: 10.1016/j.nbd.2020.104959
pmc: PMC7959200
mid: NIHMS1673682
pii:
doi:
Substances chimiques
Fmr1 protein, mouse
0
Fragile X Mental Retardation Protein
139135-51-6
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
104959Subventions
Organisme : NIDCD NIH HHS
ID : R01 DC000566
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS095311
Pays : United States
Informations de copyright
Copyright © 2020. Published by Elsevier Inc.
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