<i>Fmr1</i> KO causes delayed rebound spike timing in mediodorsal thalamocortical neurons through regulation of HCN channel activity.

ABSTRACT:

Background

The neurodevelopmental disorder Fragile X syndrome (FXS) results from hypermethylation of the FMR1 gene which prevents FMRP production. FMRP modulates the expression and function of a wide variety of proteins, including voltage-gated ion channels such as Hyperpolarization-Activated Cyclic Nucleotide gated (HCN) channels, which are integral to rhythmic activity in thalamic structures. Thalamocortical pathology, particularly involving the mediodorsal thalamus (MD), has been implicated in neurodevelopmental disorders. MD connectivity with mPFC is integral to executive functions like working memory and social behaviors that are disrupted in FXS.

Methods

We used a combination of retrograde labeling and ex vivo brain slice whole cell electrophysiology in 4

SUBMITTER: Ordemann GJ 

PROVIDER: S-EPMC11838482 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature