title: Identification of transmitter systems and learning tag molecules involved in behavioral tagging during memory formation.
abstract: Long-term memory (LTM) consolidation requires the synthesis of plasticity-related proteins (PRPs). In addition, we have shown recently that LTM formation also requires the setting of a "learning tag" able to capture those PRPs. Weak training, which results only in short-term memory, can set a tag to use PRPs derived from a temporal-spatial closely related event to promote LTM formation. Here, we studied the involvement of glutamatergic, dopaminergic, and noradrenergic inputs on the setting of an inhibitory avoidance (IA) learning tag and the synthesis of PRPs. Rats explored an open field (PRP donor) followed by weak (tag inducer) or strong (tag inducer plus PRP donor) IA training. Throughout pharmacological interventions around open-field and/or IA sessions, we found that hippocampal dopamine D1/D5- and β-adrenergic receptors are specifically required to induce PRP synthesis. Moreover, activation of the glutamatergic NMDA receptors is required for setting the learning tags, and this machinery further required α-Ca(2+)/calmodulin-dependent protein kinase II and PKA but not ERK1/2 activity. Together, the present findings emphasize an essential role of the induction of PRPs and learning tags for LTM formation. The existence of only the PRP or the tag was insufficient for stabilization of the mnemonic trace.
authors.affiliation: Facultad de Medicina, Instituto de Biología Celular y Neurociencias, Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina, CP 1121 Buenos Aires, Argentina.
authors.forename: Diego
authors.initials: D
authors.lastname: Moncada
authors.forename: Fabricio
authors.initials: F
authors.lastname: Ballarini
authors.forename: María Cecilia
authors.initials: MC
authors.lastname: Martinez
authors.forename: Julietta U
authors.initials: JU
authors.lastname: Frey
authors.forename: Haydee
authors.initials: H
authors.lastname: Viola
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D001552:Benzazepines / Q000494:pharmacology; D056547:CA1 Region, Hippocampal / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D004280:Dobutamine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005106:Exploratory Behavior / Q000502:physiology; D008297:Male; D057567:Memory, Long-Term / Q000187:drug effects / Q000502:physiology*; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D050641:Receptors, Dopamine D5 / Q000037:antagonists & inhibitors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000319:Adrenergic beta-Antagonists; D001552:Benzazepines; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D011943:Receptors, Adrenergic, beta; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; C534628:SCH 23390; C096637:2-amino-5-phosphono-3-pentenoic acid; D050641:Receptors, Dopamine D5; D004280:Dobutamine; C063302:KN 62; D015763:2-Amino-5-phosphonovalerate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011433:Propranolol; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2