PMID- 18238806
OWN - NLM
STAT- MEDLINE
DCOM- 20080623
LR  - 20220408
IS  - 1469-7793 (Electronic)
IS  - 0022-3751 (Print)
IS  - 0022-3751 (Linking)
VI  - 586
IP  - 7
DP  - 2008 Apr 1
TI  - Impaired GABAergic inhibition in the visual cortex of brain-derived neurotrophic 
      factor heterozygous knockout mice.
PG  - 1885-901
LID - 10.1113/jphysiol.2007.148627 [doi]
AB  - Brain derived neurotrophic factor (BDNF) promotes the formation, maturation and 
      stabilization of inhibitory synapses in the central nervous system. In addition, 
      BDNF has been suggested to regulate the critical period for ocular dominance 
      plasticity in the visual system. Here we further evaluated the role of BDNF in 
      the visual cortex by studying the GABAergic synaptic transmission under 
      conditions of chronically reduced levels of BDNF. Whole-cell patch-clamp 
      recordings were performed from pyramidal neurons located in layers II/III of 
      visual cortical slices in heterozygous BDNF knockout mice (BDNF (+/-)) and their 
      wild-type littermates at the age of 21-25 days. The BDNF (+/-) mice showed a 
      decreased frequency and amplitude of miniature inhibitory postsynaptic currents 
      (mIPSCs) as well as a reduced amplitude and prolonged decay time constant of 
      evoked IPSCs. Further analyses indicated an impaired presynaptic GABAergic 
      function in BDNF (+/-) mice, as shown by the decreased release probability, 
      steady-state release and synchronous release of GABA. However, the number of 
      functional release sites remained unchanged. In line with these observations, an 
      impaired glutamate-driven GABA release was observed in BDNF (+/-) mice. 
      Furthermore, the overall balance in the strength of cortical excitation to 
      inhibition shifted towards a decreased inhibition. Finally, the reversal 
      potential for chloride-mediated evoked IPSCs was not affected. These findings 
      suggested that chronically reduced levels of BDNF strongly impair the GABAergic 
      inhibitory function in visual cortex by altering postsynaptic properties and by 
      reducing presynaptic GABA release as well as the overall strength of inhibition 
      onto pyramidal neurons within the cortical network. These impairments of 
      inhibitory function are compatible with a rather immature status of the GABAergic 
      system in BDNF (+/-) mice, which supports the hypothesis that the level of 
      expression for BDNF critically affects maturation and function of the GABAergic 
      inhibition.
FAU - Abidin, Ismail
AU  - Abidin I
AD  - Department of Neurophysiology, MA 4/149, Ruhr-University Bochum, D-44780 Bochum, 
      Germany.
FAU - Eysel, Ulf T
AU  - Eysel UT
FAU - Lessmann, Volkmar
AU  - Lessmann V
FAU - Mittmann, Thomas
AU  - Mittmann T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080131
PL  - England
TA  - J Physiol
JT  - The Journal of physiology
JID - 0266262
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
SB  - IM
MH  - Action Potentials/physiology
MH  - Animals
MH  - Animals, Newborn
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - *Heterozygote
MH  - Inhibitory Postsynaptic Potentials/physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Neuronal Plasticity/physiology
MH  - Patch-Clamp Techniques
MH  - Pyramidal Cells/cytology/metabolism
MH  - Synaptic Transmission/*physiology
MH  - Visual Cortex/cytology/*metabolism
MH  - gamma-Aminobutyric Acid/*metabolism
PMC - PMC2375720
EDAT- 2008/02/02 09:00
MHDA- 2008/06/24 09:00
PMCR- 2009/04/01
CRDT- 2008/02/02 09:00
PHST- 2008/02/02 09:00 [pubmed]
PHST- 2008/06/24 09:00 [medline]
PHST- 2008/02/02 09:00 [entrez]
PHST- 2009/04/01 00:00 [pmc-release]
AID - jphysiol.2007.148627 [pii]
AID - 10.1113/jphysiol.2007.148627 [doi]
PST - ppublish
SO  - J Physiol. 2008 Apr 1;586(7):1885-901. doi: 10.1113/jphysiol.2007.148627. Epub 
      2008 Jan 31.