The entorhinal cortex plays a role in extinction.
In this study, we analyzed the participation of the entorhinal cortex in extinction of a learned aversive response. Rats with infusion cannulae aimed to the entorhinal cortex were trained in a one-trial step-down inhibitory avoidance task (IA) and submitted to four consecutive daily test sessions without the footshock, a procedure that induced extinction of the conditioned response in control animals. When infused into the entorhinal cortex immediately after the first extinction session at doses able to block consolidation of IA memory, the NMDA receptor antagonist, AP5 (25 nmol/side), the inhibitor of protein synthesis anisomycin (300 nmol/side) and the inhibitor of CaMKII, KN-93 (10 nmol/side), but not the MEK1/2 inhibitor PD-98059 (5 nmol/side) hindered extinction of the IA response. The same results were obtained when the interval between the first and second test session was 48 instead of 24h. The data indicate that normal functionality of the NMDA receptors, together with CaMKII activity and protein synthesis are necessary in the entorhinal cortex at the time of the first test session to generate extinction. Our results also suggest that the ERK1/2 pathway does not play a role in this process.
Bevilaqua
Lia R
LR
Centro de Memória, Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica de Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil.
Bonini
Juliana S
JS
Rossato
Janine I
JI
Izquierdo
Luciana A
LA
Cammarota
Martín
M
Izquierdo
Iván
I
D000679:Amygdala / Q000502:physiology; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D001931:Brain Mapping; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology*; D003214:Conditioning, Classical / Q000502:physiology; D018728:Entorhinal Cortex / Q000502:physiology*; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D007266:Inhibition, Psychological; D008297:Male; D011939:Mental Recall / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases