Disrupted inhibitory plasticity and homeostasis in Fragile X syndrome
Author
dc.contributor.author
Cea del Río, C. A.
Author
dc.contributor.author
Núñez Parra, Alexia
Author
dc.contributor.author
Freedman, S. M.
Author
dc.contributor.author
Kushner, J. K.
Author
dc.contributor.author
Alexander, A. L.
Author
dc.contributor.author
Restrepo, D.
Author
dc.contributor.author
Huntsman, M. M
Admission date
dc.date.accessioned
2020-08-31T18:58:21Z
Available date
dc.date.available
2020-08-31T18:58:21Z
Publication date
dc.date.issued
2020
Cita de ítem
dc.identifier.citation
Neurobiology of Disease 142 (2020) 104959
es_ES
Identifier
dc.identifier.other
10.1016/j.nbd.2020.104959
Identifier
dc.identifier.uri
https://repositorio.uchile.cl/handle/2250/176655
Abstract
dc.description.abstract
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.
es_ES
Patrocinador
dc.description.sponsorship
United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
R01 DC000566
R01 NS095311
FRAXA
Comisión Nacional de Investigación Científica y Tecnológica (CONICYT)
CONICYT FONDECYT
11150816