PMID- 24908484
OWN - NLM
STAT- MEDLINE
DCOM- 20140808
LR  - 20211021
IS  - 1097-4199 (Electronic)
IS  - 0896-6273 (Print)
IS  - 0896-6273 (Linking)
VI  - 82
IP  - 5
DP  - 2014 Jun 4
TI  - Non-cell-autonomous mechanism of activity-dependent neurotransmitter switching.
PG  - 1004-16
LID - S0896-6273(14)00344-4 [pii]
LID - 10.1016/j.neuron.2014.04.029 [doi]
AB  - 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 in surrounding 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.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Guemez-Gamboa, Alicia
AU  - Guemez-Gamboa A
AD  - Neurobiology Section, Division of Biological Sciences and Center for Neural 
      Circuits and Behavior, Kavli Institute for Brain and Mind, University of 
      California San Diego, La Jolla, CA 92093-0357, USA.
FAU - Xu, Lin
AU  - Xu L
AD  - Neurobiology Section, Division of Biological Sciences and Center for Neural 
      Circuits and Behavior, Kavli Institute for Brain and Mind, University of 
      California San Diego, La Jolla, CA 92093-0357, USA.
FAU - Meng, Da
AU  - Meng D
AD  - Neurobiology Section, Division of Biological Sciences and Center for Neural 
      Circuits and Behavior, Kavli Institute for Brain and Mind, University of 
      California San Diego, La Jolla, CA 92093-0357, USA.
FAU - Spitzer, Nicholas C
AU  - Spitzer NC
AD  - Neurobiology Section, Division of Biological Sciences and Center for Neural 
      Circuits and Behavior, Kavli Institute for Brain and Mind, University of 
      California San Diego, La Jolla, CA 92093-0357, USA. Electronic address: 
      nspitzer@ucsd.edu.
LA  - eng
GR  - R01 NS015918/NS/NINDS NIH HHS/United States
GR  - R56 NS015918/NS/NINDS NIH HHS/United States
GR  - R01 NS057690/NS/NINDS NIH HHS/United States
GR  - NS57690/NS/NINDS NIH HHS/United States
GR  - NS15918/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Neuron
JT  - Neuron
JID - 8809320
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Proto-Oncogene Proteins c-jun)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Calcium/metabolism
MH  - Cells, Cultured
MH  - Female
MH  - Glutamic Acid/*metabolism
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - Neurons/*metabolism
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-jun/metabolism
MH  - *Signal Transduction
MH  - Spinal Cord/*embryology/metabolism
MH  - Xenopus laevis
MH  - gamma-Aminobutyric Acid/*metabolism
PMC - PMC4072120
MID - NIHMS590700
COIS- COMPETING FINANCIAL INTERESTS The authors declare no competing financial 
      interests
EDAT- 2014/06/09 06:00
MHDA- 2014/08/13 06:00
PMCR- 2015/06/04
CRDT- 2014/06/09 06:00
PHST- 2014/04/14 00:00 [accepted]
PHST- 2014/06/09 06:00 [entrez]
PHST- 2014/06/09 06:00 [pubmed]
PHST- 2014/08/13 06:00 [medline]
PHST- 2015/06/04 00:00 [pmc-release]
AID - S0896-6273(14)00344-4 [pii]
AID - 10.1016/j.neuron.2014.04.029 [doi]
PST - ppublish
SO  - Neuron. 2014 Jun 4;82(5):1004-16. doi: 10.1016/j.neuron.2014.04.029.