Late expression of brain-derived neurotrophic factor in the amygdala is required for persistence of fear memory.
In many instances, increase in neuronal activity can induce biphasic secretion of a modulator. The initial release of the modulator triggers the induction of synaptic plasticity, whereas the second-phase release reinforces the efficacy of synaptic transmission and growth of dendrites and axons. In this study, we showed that fear conditioning not only induced the first but also a second peak of brain-derived neurotrophic factor (BDNF) expression. Fluorescent immunohistostaining confirmed that BDNF expression increased at 1 and 12 h after conditioning and returned to baseline at 30 h after conditioning. Mature BDNF expression increased in a similar manner. TrkB-IgG or K252a infusion before training impaired fear memory on days 1 and 7 after training. In contrast, TrkB-IgG or K252a infusion 9 h after fear conditioning did not affect memory retention on day 1 after training but impaired fear memory on day 7 after training. Fear conditioning significantly enhanced Zif268 expression in the amygdala at 12 h after training; this enhanced expression was completely inhibited by TrkB-IgG infusion 9 h after training. The level of growth-associated protein 43 (GAP-43), a marker of newly formed synapses, in the amygdala increased 7 days after fear conditioning. Moreover, conditioned rats had higher AMPA/NMDA ratio than unpaired rats. These results suggest that consolidated memory could be continuously modulated by previous molecular changes produced during memory acquisition.
Ou
Li-Chin
LC
Institute of Basic Medical Sciences and Department of Pharmacology, Center for Gene Regulation and Signal Transduction Research, National Cheng-Kung University, Tainan 701, Taiwan.
Yeh
Shiu-Hwa
SH
Gean
Po-Wu
PW
D000161:Acoustic Stimulation; D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism*; D002227:Carbazoles / Q000378:metabolism; D005239:Fear; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000235:genetics*; D006624:Hippocampus / Q000378:metabolism; D026121:Indole Alkaloids / Q000378:metabolism; D008297:Male; D008568:Memory / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D013216:Reflex, Startle; D015398:Signal Transduction / Q000502:physiology; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D026121:Indole Alkaloids; C049985:staurosporine aglycone; D020813:Receptor, trkB