BDNF–triggered events in the rat hippocampus are required for both short‐ and long‐term memory formation

Abstract

Information storage in the brain is a temporally graded process 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 neutrophic factor (BDNF) modulates both short-term synaptic function and activity-dependent synaptic plasticity in the adult hippocampus, we examined the role of BDNF in STM and LTM formation of a hippocampal-dependent one-trial fear-motivated learning task in rats. Using a competitive RT-PCR quantitation method, we found that inhibitory 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 CA, region of the dorsal hippocampus decreased extracellular signal-regulated kinase 2 (ERK2) activation and impaired STM retention scores. Inhibition of ERK1/2 activation by PD098059 produced similar effects. In contrast, intrahippocampal administration of recombinant human BDNF increased ERK1/2 activation and facilitated STM. The infusion of anti-BDNF antibody 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 formation. 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 inhibitory avoidance learning. Additionally, they suggest that this requirement involves ERK1/2-dependent and -independent mechanisms.

Prostaglandins are necessary and sufficient to induce contextual fear learning impairments after interleukin-1 beta injections into the dorsal hippocampus

“…In particular, we have found BDNF to be maximally induced 2 h following contextual fear conditioning (Barrientos et al, 2004) and Alonso et al (2002) has shown that BDNF is necessary for at least 4 h after training to form a long-term memory. Since PGE 2 reduces post-conditioning BDNF mRNA at 2 h, it is likely that this may be a mechanism for PGE 2 's memory impairing effects.…”

From Acquisition to Consolidation: On the Role of Brain-Derived Neurotrophic Factor Signaling in Hippocampal-Dependent Learning

“…Further support for the involvement of BDNF in the one-trial avoidance task is provided by the observation that the infusion of exogenous BDNF into the CA1 region facilitates short-term memory retention scores ( Fig. 4A; Alonso et al 2002). In additional experiments, not only did BDNF infusion elicit a rapid increase in p-ERK, but the infusion of anti-BDNF antibody decreased p-ERK (Alonso et al 2002).…”

“…Because of the involvement of the MAPK pathway in memory formation and synaptic plasticity (for review, see Sweatt 2001), and combined with the findings previously discussed regarding BDNF-LTP, this pathway seems a likely target for investigations examining the effect of BDNF in behavioral learning paradigms. In fact, recent work by Alonso et al (2002) shows the requirement of BDNF in the formation of both short-and long-term memory involving ERK-dependent and -independent mechanisms. Alonso et al (2002) show that BDNF signaling via ERK1/2 is required in a hippocampal-dependent one-trial avoidance learning paradigm in rats.…”

“…In fact, recent work by Alonso et al (2002) shows the requirement of BDNF in the formation of both short-and long-term memory involving ERK-dependent and -independent mechanisms. Alonso et al (2002) show that BDNF signaling via ERK1/2 is required in a hippocampal-dependent one-trial avoidance learning paradigm in rats. Bilateral hippocampal CA1 infusions of a function-blocking anti-BDNF antibody prior to avoidance training impaired short-term memory retention scores.…”

Mechanisms of fear extinction

“…BDNF, acting at TrkB receptors, has been implicated in LTP induction 272,273 and fear acquisition [274][275][276] Recently, Chhatwal et al 277 found evidence for a role of BDNF in fear extinction as well. These investigators reported a time-dependent upregulation of BDNF exon Vcontaining mRNA within the BLA in extinguished rats relative to nonextinguished controls.…”