Signaling mechanisms mediating BDNF modulation of memory formation in vivo in the hippocampus.
Given that brain-derived neutrophic factor (BDNF) modulates both short-term synaptic function and activity-dependent synaptic plasticity in the adult hippocampus, here we examined signaling mechanisms in vivo in the hippocampus mediating BDNF modulation of long-term memory (LTM) formation of a one-trial fear-motivated learning task in rats. Bilateral infusions of function-blocking anti-BDNF antibody into the CA1 region of the dorsal hippocampus decreased extracellular-signal regulated kinase 2 (ERK2) and CREB activation and impaired LTM retention scores. Inhibition of ERK1/2 activation by PD098059 produced similar effects and also reduced CREB phosphorylation. In contrast, intrahippocampal administration of recombinant human BDNF increased ERK1/2 and CREB activation and facilitated LTM. Activated-p38, activated-PKC isoforms, and activated-AKT were unaltered after BDNF or anti-BDNF infusion. In addition, no changes were found on alphaPKA and betaPKA catalytic subunits in nuclear samples. Thus, our results suggest that BDNF exerts its role in LTM formation in vivo in CA1 region of the hippocampus, at least in part, via CREB activation. Moreover, BDNF-induced CREB activation appears to be mediated mainly through the activation of ERK1/2 signaling pathway.
Alonso
Mariana
M
Instituto de Biologia Celular y Neurociencias, Facultad de Medicina, UBA, Buenos Aires, Argentina.
Vianna
Monica R M
MR
Izquierdo
Ivan
I
Medina
Jorge H
JH
D000818:Animals; D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor / Q000037:antagonists & inhibitors / Q000172:deficiency*; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005239:Fear / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology*; D007858:Learning / Q000187:drug effects / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000494:pharmacology
D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D011993:Recombinant Fusion Proteins; D020928:Mitogen-Activated Protein Kinases