Format

Send to

Choose Destination
Neuron. 2013 Feb 20;77(4):696-711. doi: 10.1016/j.neuron.2012.12.018.

FMRP regulates neurotransmitter release and synaptic information transmission by modulating action potential duration via BK channels.

Author information

1
Departments of Biomedical Engineering and Cell Biology and Physiology, CIMED, Washington University, St. Louis, MO 63110, USA.

Erratum in

  • Neuron. 2013 Apr 10;78(1):205.

Abstract

Loss of FMRP causes fragile X syndrome (FXS), but the physiological functions of FMRP remain highly debatable. Here we show that FMRP regulates neurotransmitter release in CA3 pyramidal neurons by modulating action potential (AP) duration. Loss of FMRP leads to excessive AP broadening during repetitive activity, enhanced presynaptic calcium influx, and elevated neurotransmitter release. The AP broadening defects caused by FMRP loss have a cell-autonomous presynaptic origin and can be acutely rescued in postnatal neurons. These presynaptic actions of FMRP are translation independent and are mediated selectively by BK channels via interaction of FMRP with BK channel's regulatory β4 subunits. Information-theoretical analysis demonstrates that loss of these FMRP functions causes marked dysregulation of synaptic information transmission. FMRP-dependent AP broadening is not limited to the hippocampus, but also occurs in cortical pyramidal neurons. Our results thus suggest major translation-independent presynaptic functions of FMRP that may have important implications for understanding FXS neuropathology.

PMID:
23439122
PMCID:
PMC3584349
DOI:
10.1016/j.neuron.2012.12.018
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center