The robust translocation of MAPK during synaptic plasticity (11xMartin, K.C, Michael, D, Rose, J.C, Barad, M, Casadio, A, Zhu, H, and Kandel, E.R. Neuron. 1997; 18: 899–912Abstract | Full Text | Full Text PDF | PubMed | Scopus (411)See all References, 9xImpey, S, Obrietan, K, Wong, S.T, Poser, S, Yano, S, Wayman, G, Deloulme, J.C, Chan, G, and Storm, D.R. Neuron. 1998; 21: 869–883Abstract | Full Text | Full Text PDF | PubMed | Scopus (644)See all References, 15xSgambato, V, Pages, C, Rogard, M, Besson, M.J, and Caboche, J. J. Neurosci. 1998; 18: 8814–8825PubMedSee all References) indicates that there are likely additional nuclear targets of MAPK signaling other than CREB. For example, several recent reports suggest that the transcription factor Elk1 is a major nuclear target of MAPK during synaptic plasticity and memory consolidation (2xBerman, D.E, Hazvi, S, Rosenblum, K, Seger, R, and Dudai, Y. J. Neurosci. 1998; 18: 10037–10044PubMedSee all References, 15xSgambato, V, Pages, C, Rogard, M, Besson, M.J, and Caboche, J. J. Neurosci. 1998; 18: 8814–8825PubMedSee all References).The prominent dendritic localization of activated MAPK following synaptic activity (Impey et al. 1998xImpey, S, Obrietan, K, Wong, S.T, Poser, S, Yano, S, Wayman, G, Deloulme, J.C, Chan, G, and Storm, D.R. Neuron. 1998; 21: 869–883Abstract | Full Text | Full Text PDF | PubMed | Scopus (644)See all ReferencesImpey et al. 1998) suggests that it may also have important cytosolic targets. The best example of such a target is the Aplysia cell adhesion molecule ApCAM. MAPK activity is required for the downregulation and internalization of ApCAM, a key step in the induction of LTF. This is an important observation because the Drosophila (Fas II) and murine (NCAM) homologs of ApCAM have also been implicated in neuronal plasticity.Collectively, these studies indicate that the MAPK pathway is a fundamental component of LTM formation in invertebrates and vertebrates. Thus, the MAPK cascade joins the cAMP/PKA pathway and the CREB transcriptional pathway as an evolutionarily conserved regulator of LTM consolidation (Figure 1Figure 1). Work showing that MAPK is a major activator of plasticity-associated CREB-dependent gene expression also strongly suggests that MAPK signaling facilitates memory consolidation and L-LTP by promoting de novo CREB-regulated gene expression. There are a number of unanswered questions regarding the role of MAPK in neuronal plasticity and memory formation. Is CREB a target of Ras/MAPK signaling during memory consolidation? How is MAPK activated during adaptive neuronal plasticity and memory consolidation? What are the cytosolic and nuclear targets of MAPK that facilitate memory formation and modulate synaptic efficacy? Additional research using temporally and spatially restricted transgenic technologies should help clarify and confirm the role of Ras/MAPK signaling in LTM.*To whom correspondence should be addressed (e-mail: firstname.lastname@example.org).