Non-cell-autonomous mechanism of activity-dependent neurotransmitter switching

Alicia Guemez-Gamboa, Lin Xu, Da Meng, Nicholas C. Spitzer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Activity-dependent neurotransmitter switching engages genetic programs regulating transmitter synthesis, but the mechanism by which activity is transduced is unknown. We suppressed activity in single neurons in the embryonic spinal cord to determine whether glutamate-gamma-aminobutyric acid (GABA) switching is cell autonomous. Transmitter respecification did not occur, suggesting that it is homeostatically regulated by the level of activity insurrounding neurons. Graded increase in the number of silenced neurons in cultures led to graded decrease in the number of neurons expressing GABA, supporting non-cell-autonomous transmitter switching. We found that brain-derived neurotrophic factor (BDNF) is expressed in the spinal cord during the period of transmitter respecification and that spike activity causes release of BDNF. Activation of TrkB receptors triggers a signaling cascade involving JNK-mediated activation of cJun that regulates tlx3, a glutamate/GABA selector gene, accounting for calcium-spike BDNF-dependent transmitter switching. Our findings identify a molecular mechanism for activity-dependent respecification of neurotransmitter phenotype in developing spinal neurons.

Original languageEnglish (US)
Pages (from-to)1004-1016
Number of pages13
JournalNeuron
Volume82
Issue number5
DOIs
StatePublished - Jun 4 2014

ASJC Scopus subject areas

  • Neuroscience(all)

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