PMID- 23964198
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20130821
LR  - 20211021
IS  - 1662-5102 (Print)
IS  - 1662-5102 (Electronic)
IS  - 1662-5102 (Linking)
VI  - 7
DP  - 2013
TI  - Thyroid hormone-dependent development of early cortical networks: temporal 
      specificity and the contribution of trkB and mTOR pathways.
PG  - 121
LID - 10.3389/fncel.2013.00121 [doi]
LID - 121
AB  - Early in neocortical network development, triiodothyronine (T3) promotes 
      GABAergic neurons' population increase, their somatic growth and the formation of 
      GABAergic synapses. In the presence of T3, GABAergic interneurons form longer 
      axons and conspicuous axonal arborizations, with an increased number of putative 
      synaptic boutons. Here we show that the increased GABAergic axonal growth is 
      positively correlated with the proximity to non-GABAergic neurons (non-GABA). A 
      differential innervation emerges from a T3-dependent decrease of axonal length in 
      fields with low density of neuronal cell bodies, combined with an increased 
      bouton formation in fields with high density of neuronal somata. T3 addition to 
      deprived networks after the first 2 weeks of development did not rescue deficits 
      in the GABAergic synaptic bouton distribution, or in the frequency and duration 
      of spontaneous bursts. During the critical 2-week-period, GABAergic signaling is 
      depolarizing as revealed by calcium imaging experiments. Interestingly, T3 
      enhanced the expression of the potassium-chloride cotransporter 2 (KCC2), and 
      accelerated the developmental shift from depolarizing to hyperpolarizing 
      GABAergic signaling in non-GABA. The T3-related increase of spontaneous network 
      activity was remarkably reduced after blockade of either tropomyosin-receptor 
      kinase B (trkB) or mammalian target of rapamycin (mTOR) pathways. T3-dependent 
      increase in GABAergic neurons' soma size was mediated mainly by mTOR signaling. 
      Conversely, the T3-dependent selective increase of GABAergic boutons near 
      non-GABAergic cell bodies is mediated by trkB signaling only. Both trkB and mTOR 
      signaling mediate T3-dependent reduction of the GABAergic axon extension. The 
      circuitry context is relevant for the interaction between T3 and trkB signaling, 
      but not for the interactions between T3 and mTOR signaling.
FAU - Westerholz, Soren
AU  - Westerholz S
AD  - Institute of Physiology, Otto-von-Guericke University Magdeburg, Germany.
FAU - de Lima, Ana D
AU  - de Lima AD
FAU - Voigt, Thomas
AU  - Voigt T
LA  - eng
PT  - Journal Article
DEP - 20130806
PL  - Switzerland
TA  - Front Cell Neurosci
JT  - Frontiers in cellular neuroscience
JID - 101477935
PMC - PMC3734363
OTO - NOTNLM
OT  - BDNF
OT  - GABA
OT  - KCC2
OT  - NKCC1
OT  - interneurons
OT  - mTOR
OT  - neocortex
OT  - triiodothyronine
EDAT- 2013/08/22 06:00
MHDA- 2013/08/22 06:01
PMCR- 2013/01/01
CRDT- 2013/08/22 06:00
PHST- 2013/03/20 00:00 [received]
PHST- 2013/07/10 00:00 [accepted]
PHST- 2013/08/22 06:00 [entrez]
PHST- 2013/08/22 06:00 [pubmed]
PHST- 2013/08/22 06:01 [medline]
PHST- 2013/01/01 00:00 [pmc-release]
AID - 10.3389/fncel.2013.00121 [doi]
PST - epublish
SO  - Front Cell Neurosci. 2013 Aug 6;7:121. doi: 10.3389/fncel.2013.00121. eCollection 
      2013.