Selective impact of MeCP2 and associated histone deacetylases on the dynamics of evoked excitatory neurotransmission

Erika D. Nelson, Manjot Bal, Ege T Kavalali, Lisa M Monteggia

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

An imbalance between the strengths of excitatory and inhibitory synaptic inputs has been proposed as the cellular basis of autism and related neurodevelopmental disorders. Previous studies examining spontaneous levels of excitatory and inhibitory neurotransmission in the forebrain regions of methyl-CpG-binding protein 2 (Mecp2) mutant mice, models of the autism spectrum disorder Rett syndrome, have identified a decrease in excitatory drive, in some cases coupled with an increase in inhibitory synaptic strength, as a major source of this imbalance. Here, we reevaluated this question by examining the short-term dynamics of evoked neurotransmission between hippocampal neurons cultured from MeCP2 knockout mice and found a marked increase in evoked excitatory neurotransmission that is consistent with an increase in presynaptic release probability. This increase in evoked excitatory drive was not matched with alterations in evoked inhibitory neurotransmission. Moreover, we observed similar excitatory drive specific changes after the loss of key histone deacetylases (histone deacetylase 1 and 2) that form a complex with MeCP2 and mediate transcriptional regulation. These findings suggest a distinct role for MeCP2 and its cofactors in the regulation of evoked excitatory neurotransmission compared with their essential role in basal synaptic activity.

Original languageEnglish (US)
Pages (from-to)193-201
Number of pages9
JournalJournal of Neurophysiology
Volume106
Issue number1
DOIs
StatePublished - Jul 2011

Fingerprint

Histone Deacetylases
Synaptic Transmission
Histone Deacetylase 2
Histone Deacetylase 1
Rett Syndrome
Autistic Disorder
Prosencephalon
Knockout Mice
Neurons
Drive

Keywords

  • Knockout
  • Methyl-cpg-binding protein 2
  • Rett syndrome
  • Synaptic neurotransmission
  • Transcriptional repression

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

Cite this

Selective impact of MeCP2 and associated histone deacetylases on the dynamics of evoked excitatory neurotransmission. / Nelson, Erika D.; Bal, Manjot; Kavalali, Ege T; Monteggia, Lisa M.

In: Journal of Neurophysiology, Vol. 106, No. 1, 07.2011, p. 193-201.

Research output: Contribution to journalArticle

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