SPECIFIC AND DIFFERENTIAL ACTIVATION OF MITOGEN-ACTIVATED PROTEIN-KINASE CASCADES BY UNFAMILIAR TASTE IN THE INSULAR CORTEX OF THE BEHAVINGRAT

Rats were given to drink an unfamiliar taste solution under conditions that result in long-term memory of that taste. The insular cortex, wh ich contains the taste cortex, was then removed and assayed for activa tion of mitogen-activated protein kinase (MAPK) cascades by using anti bodies to the activated forms of various MAPKs. Extracellular responsi ve kinase 1-2 (ERK1-2) in the cortical homogenate was significantly ac tivated within <30 min of drinking the taste solution, without alterat ion in the total level of the ERK1-2 proteins. The activity subsided t o basal levels within <60 min. In contrast, ERK1-2 was not activated w hen the taste was made familiar. The effect of the unfamiliar taste wa s specific to the insular cortex. Jun N-terminal kinase 1-2 (JNK1-2) w as activated by drinking the taste but with a delayed time course, whe reas the activity of Akt kinase and p38MAPK remained unchanged. Elk-1, a member of the ternary complex factor and an ERK/JNK downstream subs trate, was activated with a time course similar to that of ERK1-2. Mic roinjection of a reversible inhibitor of MAPK/ERK kinase into the insu lar cortex shortly before exposure to the novel taste in a conditioned taste aversion training paradigm attenuated long-term taste aversion memory without significantly affecting short-term memory or the sensor y, motor, and motivational faculties required to express long-term tas te aversion memory. It was concluded that ERK and JNK are specifically and differentially activated in the insular cortex after exposure to a novel taste, and that this activation is required for consolidation of long-term taste memory.