Molecular mechanisms in hippocampus and basolateral amygdala but not in parietal or cingulate cortex are involved in extinction of one-trial avoidance learning.
The establishment of extinction of one-trial avoidance involves the dorsal hippocampus (DH) and basolateral amygdala (BLA), two areas that participate in its original consolidation. The posterior parietal (PARIE) and posterior cingulate (CING) cortices also participate in consolidation of this task but their role in extinction has not been explored. Here we study the effect on the extinction of one-trial avoidance in rats of three different drugs infused bilaterally into DH, BLA, PARIE or CING 5min before the first of four daily unreinforced test sessions: The glutamate NMDA receptor antagonist, AP5 (5.0microg/side),and the inhibitors of calcium-calmodulin dependent kinase II (CaMKII), KN-93 (0.3microg/side), or of the cAMP-dependent protein kinase (PKA), Rp-cAMPs (0.5microg/side) hindered extinction when given into DH or BLA. Levels of pPKA and pCaMKII increased in DH after the first extinction trial; in BLA only the CaMKII increase was seen. Thus, this pathway appears to participate in extinction in BLA at the "basal" levels, and at enhanced levels in DH. None of the treatments affected extinction when given into PARIE or CING. The present findings indicate that: (1) the DH and BLA are important for the initiation of extinction at the time of the first unreinforced retrieval session; (2) both the CaMKII and the PKA signaling pathway are necessary for the development of extinction in the two regions; (3) PARIE and CING are probably unrelated to extinction.
Myskiw
Jociane C
JC
Centro de Memória, Instituto do Cérebro, Pontifical Catholic University of Rio Grande do Sul, Av. Ipiranga 6690, 2nd floor, 90610-000 Porto Alegre, RS, Brazil.
Fiorenza
Natalia G
NG
Izquierdo
Luciana A
LA
Izquierdo
Ivan
I
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000679:Amygdala / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D001596:Benzylamines / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D006179:Gyrus Cinguli / Q000187:drug effects / Q000201:enzymology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008845:Microinjections; D010296:Parietal Lobe / Q000187:drug effects / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D000096926:Benzenesulfonamides
D015763:2-Amino-5-phosphonovalerate; D001596:Benzylamines; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D018691:Excitatory Amino Acid Antagonists; D047428:Protein Kinase Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; D013449:Sulfonamides; D013873:Thionucleotides; C072105:KN 93; D000096926:Benzenesulfonamides; C016957:adenosine-3',5'-cyclic phosphorothioate