BDNF–Triggered Events in the Rat Hippocampus Are Required for Both Short- and Long-Term Memory Formation

MARIANA ALONSO; MONICA R.M. VIANNA; AMAICHA M. DEPINO; TADEU MELLO E SOUZA; PATRICIA PEREIRA; GERMAN SZAPIRO; HAYDEE VIOLA; FERNANDO PITOSSI; IVAN IZQUIERDO; JORGE H. MEDINA

HIPPOCAMPUS

WILEY-LISS, DIV JOHN WILEY & SONS INC

Lugar: New York; Año: 2002 p. 551 - 560

1050-9631

Information  storage in the brain is a temporally graded pro- cess involving different memory types or phases. It has been assumed for over a century that one or more short-term memory (STM) processes are involved in processing  new information  while long-term  memory (LTM) is  being formed.  Because brain-derived  neutrophicfactor (BDNF) modulates  both short-term synapticfunction and activity-dependent synaptic plasticity in the adult hippocampus, we examined the role of BDNF in STM and LTM forma- tion of a hippocampal-dependent  one-trial  fear-motivated  learning task in rats. Using acompetitive RT-PCR quantitation method, we found that inhib- itory avoidance training is associated with a rapid and transient increase in BDNF mRNA expression in the hippocampus. Bilateral infusions of function- blocking anti-BDNF antibody into the CA1 region of the dorsal hippocampus decreased extracellular  signal–regulated kinase 2 (ERK2) activationand im- paired STM retention scores. Inhibition  of ERK1/2 activationby PD098059 produced similar effects. In contrast, intrahippocampal  administration  of recombinant human BDNF increasedERK1/2 activation and facilitated STM. The infusion of anti-BDNFantibody impaired LTM when given 15 min before or 1 and 4 hr after training, but not at 0 or 6 hr posttraining, indicating that two hippocampal BDNF-sensitive time windows are critical for LTM forma- tion. At the same time points,PD098059 produced no LTM deficits. Thus, our results indicate that endogenous BDNF is required for both STM and LTM formation of an inhibitoryavoidance learning. Additionally, they suggest that this requirement involves ERK1/2-dependent and -independent mechanisms