Specific and Differential Activation of Mitogen-Activated Protein Kinase Cascades by Unfamiliar Taste in the Insular Cortex of the Behaving Rat

Abstract

Rats were given to drink an unfamiliar taste solution under conditions that result in long-term memory of that taste. The insular cortex, which contains the taste cortex, was then removed and assayed for activation of mitogen-activated protein kinase (MAPK) cascades by using antibodies to the activated forms of various MAPKs. Extracellular responsive kinase 1-2 (ERK1-2) in the cortical homogenate was significantly activated within Ͻ30 min of drinking the taste solution, without alteration in the total level of the ERK1-2 proteins. The activity subsided to basal levels within Ͻ60 min. In contrast, ERK1-2 was not activated when the taste was made familiar. The effect of the unfamiliar taste was specific to the insular cortex. Jun N-terminal kinase 1-2 (JNK1-2) was activated by drinking the taste but with a delayed time course, whereas the activity of Akt kinase and p38MAPK remained unchanged. Elk-1, a member of the ternary complex factor and an ERK/JNK downstream substrate, was activated with a time course similar to that of ERK1-2. Microinjection of a reversible inhibitor of MAPK/ERK kinase into the insular 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 sensory, motor, and motivational faculties required to express long-term taste 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.

Regulated transcription of the immediate‐early gene Zif268: Mechanisms and gene dosage‐dependent function in synaptic plasticity and memory formation

“…Similar results have been obtained in the lateral nucleus of the amygdala in the consolidation of fear memory (Schafe et al, 2000), where Zif268 is also activated (Hall et al, 2000;Malkani and Rosen, 2000). Moreover, coordinated activation of MAPK/ ERK, CREB and Elk-1 has also been reported in the hippocampus after one-trial avoidance learning (Cammarota et al, 2000) and in the insular cortex in association with long-term storage of taste memory (Berman et al, 1998). Together, these data suggest, but do not prove, that the same transduction mechanisms via the MAPK/ERK cascade that are implicated in LTP, are recruited in different structures and pathways to mediate learning-induced Zif268 expression.…”

“…A crucial event in signal transduction leading to gene regulation in neurons is the activation of protein kinases. Although several kinases, including protein kinase C (PKC), protein kinase A (PKA), ␣-calmodulin protein kinase II (␣CaMKII), and the tyrosine kinases, are known to play an important role in LTP (for review, see Soderling and Derkach, 2000), recent work suggests that the MAPK/ERK cascade, a complex kinase cascade implicated in cell differentiation and proliferation, is essential for long-term synaptic plasticity Sweatt, 1996, 1997) and for certain types of learning (Berman et al, 1998;Atkins et al, 1998;Blum et al, 1999), and is a likely candidate for mediating the transcriptional response associated with synaptic plasticity. In cell lines, experimental evidence suggests that MAPK/ERK, once activated, translocates to the nucleus where it can regulate transcriptional activity of many IEGs (reviewed in Treisman, 1996).…”

Extracellular Signal-Regulated Kinase Activity in the Entorhinal Cortex Is Necessary for Long-Term Spatial Memory

“…For example, our laboratory has shown that intrahippocampal PD098059 administration blocks longterm memory in the water maze task without any effect on short-term memory (Blum et al 1999). In addition, it has been reported that PD098059 administration blocks longterm memory in taste aversion, fear conditioning, and passive avoidance tasks (Berman et al 1998;Schafe et al 1999;Walz et al 1999). In this report, we have used PD098059 to investigate the role of Erk activity in the EC in long-term spatial memory.…”

NMDA Partial Agonist Reverses Blocking of Extinction of Aversive Memory by GABAA Agonist in the Amygdala

“…This test session is defined as extinction training since animals are exposed to nonreinforced presentations of a conditioned stimulus (CS; eg, saccahrine) that had previously been paired with a fear-inducing unconditioned stimulus (US; eg, LiCl). Under these conditions, the conditioned rats preferred water to saccharin at a ratio of 9:1 in a multiple choice test situation (Berman et al, 1998). Multiple-bottle tests are more sensitive than one-bottle tests to obtain an aversion index.…”