Identification of transmitter systems and learning tag molecules involved in behavioral tagging during memory formation

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 108; no. 31; pp. 12931 - 12936
• Main Authors: Moncada, Diego, Ballarini, Fabricio, Martinez, María Cecilia, Frey, Julietta U, Viola, Haydee
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 02.08.2011; National Acad Sciences
• Subjects: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - analogs & derivatives; 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology; 2-Amino-5-phosphonovalerate - analogs & derivatives; 2-Amino-5-phosphonovalerate - pharmacology; Adrenergic beta-Antagonists - pharmacology; Animal memory; Animals; Avoidance learning; Avoidance Learning - physiology; Benzazepines - pharmacology; Biological Sciences; CA1 Region, Hippocampal - metabolism; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - antagonists & inhibitors; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism; cAMP-dependent protein kinase; Dentate gyrus; Dobutamine - pharmacology; dopamine; Dopamine D1 receptors; Dopamine D5 receptors; Enzyme Inhibitors - pharmacology; Excitatory Amino Acid Antagonists - pharmacology; Exploratory Behavior - physiology; Extracellular signal-regulated kinase; Glutamatergic transmission; Glutamic acid receptors (ionotropic); Hippocampus; Learning; Long term memory; Long term potentiation; Male; Memory; Memory, Long-Term - drug effects; Memory, Long-Term - physiology; Memory, Short-Term - drug effects; Memory, Short-Term - physiology; Molecules; N methyl D aspartate receptors; N-Methyl-D-aspartic acid receptors; Neuronal Plasticity - physiology; Neurotransmitters; Norepinephrine; Propranolol - pharmacology; Protein kinase A; Protein synthesis; Proteins; Rats; Rats, Wistar; Receptors; Receptors, Adrenergic, beta - metabolism; Receptors, Dopamine D1 - antagonists & inhibitors; Receptors, Dopamine D1 - metabolism; Receptors, Dopamine D5 - antagonists & inhibitors; Receptors, Dopamine D5 - metabolism; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - metabolism; Rodents; Short term memory; Training; Vehicles
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1104495108

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-Ca²⁺/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.