PMID- 10601005
OWN - NLM
STAT- MEDLINE
DCOM- 20000131
LR  - 20190513
IS  - 1047-3211 (Print)
IS  - 1047-3211 (Linking)
VI  - 9
IP  - 8
DP  - 1999 Dec
TI  - Development of neuronal activity and activity-dependent expression of 
      brain-derived neurotrophic factor mRNA in organotypic cultures of rat visual 
      cortex.
PG  - 864-77
AB  - We have analyzed in organotypic rat visual cortex cultures the way in which 
      expression of brain-derived neurotrophic factor (BDNF) mRNA depends on 
      synaptically generated spontaneous bioelectric activity (SBA) as monitored by 
      recordings of pyramidal cells. SBA was initially low, but from the fourth week 
      onwards 83% of the neurons fired action potentials at 0.2-1.2 impulses/s in a 
      well-balanced state of excitation and inhibition. BDNF mRNA expression increased 
      during the second week to a level surprisingly similar to the adult visual cortex 
      in vivo, despite the fact that activity rates in vitro were approximately 10-fold 
      lower than rates reported in vivo. Thus, SBA generated by a cortical neuronal 
      network in the absence of sensory input is sufficient to elicit and maintain BDNF 
      expression. The transient BDNF peak occurring after eye opening in vivo did not 
      occur in vitro. A blockade of SBA seems not to alter the expression of 
      neurotrophin (NT)-3 and -4/5, and tyrosine kinase receptor C and B mRNA. However, 
      BDNF expression remained extremely low. A recovery of SBA after a period of 
      blockade concurred with a transient hyperexcitability. BDNF immediately 
      increased, driven by calcium influx through voltage-gated channels in synergy 
      with NMDA receptors. Expression transiently reached high levels in neurons of 
      supragranular layers. Infragranular neurons, although firing action potentials, 
      recovered BDNF expression much slower. After 5 days in vitro recovery, the 
      network had de novo established a balanced state of excitation and inhibition. 
      Distribution and expression level of BDNF mRNA had returned to control. Even in 
      'adult' cultures an acute blockade of SBA downregulated BDNF, and a subsequent 
      recovery of SBA restored BDNF expression. We conclude that BDNF mRNA expression 
      depends on and responds with a fast kinetic to changes of the SBA. Steady-state 
      levels do not depend on the absolute levels of activity, but more likely on the 
      balance between excitation and inhibition, suggesting a role for BDNF in activity 
      homeostasis.
FAU - Gorba, T
AU  - Gorba T
AD  - AG Entwicklungsneurobiologie, Fakultat fur Biologie, Ruhr-Universitat, Bochum, 
      Germany.
FAU - Klostermann, O
AU  - Klostermann O
FAU - Wahle, P
AU  - Wahle P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cereb Cortex
JT  - Cerebral cortex (New York, N.Y. : 1991)
JID - 9110718
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (GABA Antagonists)
RN  - 0 (RNA, Messenger)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - Y37615DVKC (Bicuculline)
SB  - IM
MH  - Action Potentials/drug effects/*physiology
MH  - Animals
MH  - Bicuculline/pharmacology
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - GABA Antagonists/pharmacology
MH  - Pyramidal Cells/drug effects/*metabolism
MH  - RNA, Messenger/*metabolism
MH  - Rats
MH  - Rats, Long-Evans
MH  - Visual Cortex/drug effects/*metabolism
MH  - gamma-Aminobutyric Acid/pharmacology
EDAT- 1999/12/22 00:00
MHDA- 1999/12/22 00:01
CRDT- 1999/12/22 00:00
PHST- 1999/12/22 00:00 [pubmed]
PHST- 1999/12/22 00:01 [medline]
PHST- 1999/12/22 00:00 [entrez]
AID - 10.1093/cercor/9.8.864 [doi]
PST - ppublish
SO  - Cereb Cortex. 1999 Dec;9(8):864-77. doi: 10.1093/cercor/9.8.864.