Brain-Derived Neurotrophic Factor Triggers Transcription-Dependent, Late Phase Long-Term PotentiationIn Vivo

Abstract

Acute intrahippocampal infusion of brain-derived neurotrophic factor (BDNF) leads to long-term potentiation (BDNF-LTP) of synaptic transmission at medial perforant path3granule cell synapses in the rat dentate gyrus. Endogenous BDNF is implicated in the maintenance of high-frequency stimulation-induced LTP (HFS-LTP). However, the relationship between exogenous BDNF-LTP and HFS-LTP is unclear. First, we found that BDNF-LTP, like HFS-LTP, is associated with enhancement in both synaptic strength and granule cell excitability (EPSP-spike coupling). Second, treatment with a competitive NMDA receptor (NMDAR) antagonist blocked HFS-LTP but had no effect on the development or magnitude of BDNF-LTP. Thus, NMDAR activation is not required for the induction or expression of BDNF-LTP. Formation of stable, late phase HFS-LTP requires mRNA synthesis and is coupled to upregulation of the immediate early gene activityregulated cytoskeleton-associated protein (Arc). Local infusion of the transcription inhibitor actinomycin D (ACD) 1 hr before or immediately before BDNF infusion inhibited BDNF-LTP and upregulation of Arc protein expression. ACD applied 2 hr after BDNF infusion had no effect, defining a critical time window of transcription-dependent synaptic strengthening. Finally, the functional role of BDNF-LTP was assessed in occlusion experiments with HFS-LTP. HFS-LTP was induced, and BDNF was infused at time points corresponding to early phase (1 hr) or late phase (4 hr) HFS-LTP. BDNF applied during the early phase led to normal BDNF-LTP. In contrast, BDNF-LTP was completely occluded during the late phase. The results strongly support a role for BDNF in triggering transcription-dependent, late phase LTP in the intact adult brain.

Coordinate action of pre- and postsynaptic brain-derived neurotrophic factor is required for AMPAR trafficking and acquisition of in vitro classical conditioning

“…Consistent with our findings on conditioning, LTP induction increases BDNF expression in the dentate gyrus of the hippocampus (Gooney and Lynch, 2001), fear conditioning results in enhanced expression of BDNF mRNA and activation of TrkB receptors (Rattiner et al, 2004), and activation of TrkB underlies long-term synaptic facilitation and memory in Aplysia (Sharma et al, 2006). BDNF infusion appears to enhance synaptic transmission (BDNF-LTP; Messaoudi et al, 2002, see also Lu et al, 2008. Analysis of LTP in hippocampal slices further demonstrated that application of repetitive depolarizing pulses failed to induce LTP in TrkB-IgG-incubated slices, whereas TrkA and TrkC-IgG had no effect (Gubellini et al, 2005, also Korte et al, 1998.…”

BDNF-stimulated intracellular signalling mechanisms underlie exercise-induced improvement in spatial memory in the male Wistar rat

“…Rats were housed in groups of three, provided with food and water ad libitum and experienced a 12:12-h light-dark cycle in a temperature-controlled environment (20)(21)(22) • C). All experiments were conducted under national law and European Union directives on animal experiments.…”

“…Cytochrome c was injected as it is a soluble small molecular weight protein that is inactive extracellularly [20]. The molecular weight is similar to that of BDNF, and it is often used as a control for injecting BDNF into the brain [16,21,22]. 30 min post-injection, all animals were trained in the object displacement task, and tested 24 h later.…”

Relapse to cocaine seeking increases activity-regulated gene expression differentially in the prefrontal cortex of abstinent rats

“…BDNF promotes synaptic plasticity and synaptic consolidation that are dependent upon the transcription and translation of arc (Kang and Schuman 1996;Guzowski et al 2001;Messaoudi et al 2002;Bramham and Messaoudi 2005;Soule et al 2006;Wibrand et al 2006). Thus, an increase in bdnf mRNA in the cortex may drive the arc response by initiating translation of newly synthesized arc mRNA in activated dendritic spines (Yin et al 2002;Ying et al 2002).…”