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Using infusions of protein synthesis inhibitors, antisense oligonucleotide targeting brain-derived neurotrophic factor (BDNF) mRNA or tPA-STOP (an inhibitor of the proteolysis of BDNF protein) into the hippocampus of the awake rat, we show that acquisition and extinction of contextual fear memory depended on the increased and decreased proteolysis of proBDNF (precursor BDNF) in the hippocampus, respectively.

Philip Barnes et al.

PLoS ONE 3 (9), 24 Sep 2008

Surgery, ODN, ANI and tPA STOP infusions, and histological assessment of cannula placement Performed as described by [24] with the exception that the rats were anaesthetised using isoflurane [flow rates: -oxygen; 0.8 liter/minute, NO 2 ; 0.4 litre/minute] and were implanted with stainless steel double guide cannulae (Plastics One, 22 gauge, 3.8 mm centre-to centre, 3 mm below pedestal) aimed at the dorsal hippocampus (AP -3.50, relative to bregma).

Philip Barnes et al.

PLoS ONE 3 (9), 24 Sep 2008

Anisomycin (ANI, 80 mg/ml, Sigma) and tPA-STOP (4 mM, ADI) was dissolved in sterile PBS.

Philip Barnes et al.

PLoS ONE 3 (9), 24 Sep 2008

ODNs (1.0 µl per side; 0.125 µl/min) or tPA-STOP (1.5 µl per side; 0.125 µl/min) were infused 90 min prior to conditioning or context reexposure, and ANI (1.0 µl per side; 0.5 µl/min) were infused immediately after context reexposure.

Philip Barnes et al.

PLoS ONE 3 (9), 24 Sep 2008

Extinction is correlated with Decreased Processing of BDNF in CA1 To test the hypothesis that the extinction of fear memories is mediated by the proteolytic processing of proBDNF, the synthetic competitive inhibitor of tPA, tPA-STOP Extinction is correlated with Decreased Processing- of BDNF in CA1 To test the hypothesis that the e-xtinction of fear memories is mediated by the prot-eolytic processing of proBDNF, the synthetic compe-titive inhibitor of tPA, tPA-STOP (2,7-bis-4(amidi-no-benzylidene)-cycloheptanone-1-dihydochloride) -[38] was infused into the hippoca-mpus prior to extinction training. [38] was infused into the hippocampus prior to extinction training.

Philip Barnes et al.

PLoS ONE 3 (9), 24 Sep 2008

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