Growth factor signaling and memory formation: temporal and spatial integration of a molecular network

Abstract

Growth factor (GF) signaling is critically important for developmental plasticity. It also plays a crucial role in adult plasticity, such as that required for memory formation. Although different GFs interact with receptors containing distinct types of kinase domains, they typically signal through converging intracellular cascades (e.g., Ras–MEK–MAPK) to mediate overlapping functional endpoints. Several GFs have been implicated in memory formation, but due to a high level of convergent signaling, the unique contributions of individual GFs as well as the interactions between GF signaling cascades during the induction of memory is not well known. In this review, we highlight the unique roles of specific GFs in dendritic plasticity, and discuss the spatial and temporal profiles of different GFs during memory formation. Collectively, the data suggest that the roles of GF signaling in long-lasting behavioral and structural plasticity may be best viewed as interactive components in a complex molecular network.

Distinct Growth Factor Families Are Recruited in Unique Spatiotemporal Domains during Long-Term Memory Formation in Aplysia californica

“…Our data are consistent with the emerging evidence indicating that similar temporal and spatial regulation of GF signaling occurs during memory formation (Kopec and Carew, 2013). …”

“…These data thus support the notion (Kopec and Carew, 2013) that GFs do not act in isolation, but rather act as a complex, spatiotemporally regulated molecular network that is engaged in the service of information storage within a neural circuit.…”

“…For example, short-term memory (STM) is mediated by post-translational modifications and lasts minutes to hours, whereas long-term memory (LTM) requires both translation and transcription and can last for several days or longer (Bailey et al, 1996; Castellucci et al, 1989). Intriguingly, while a variety of GFs have been implicated in learning and memory processes, no individual GF can, by itself, support all the plastic changes that occur during memory formation (Kopec and Carew, 2013). Moreover, there is considerable overlap in the roles that different GFs play as critical mediators of plasticity, and their effects are exerted by engaging highly convergent molecular signaling cascades (Huang and Reichardt, 2003; Massague, 2000).…”

The Contribution of Spatial and Temporal Molecular Networks in the Induction of Long-term Memory and Its Underlying Synaptic Plasticity

“…GF signaling cascades are tightly regulated in both space and time during developmental plasticity in order to create precise neural circuits [89–91], and these same principles are at play during GF regulation of learning and memory formation [92]. GF signaling thus affords an ideal opportunity to demonstrate the concept of temporal and spatial networks in learning and memory.…”

“…Importantly, the high level of interaction between intracellular signaling cascades, including the kinases reviewed here, would predict that interactions also occur between multiple upstream signaling activators, like GFs. Indeed, a wide variety of GFs are engaged in learning and memory formation, and no GF by itself can mediate the complex molecular and cellular outcomes critical for long-lasting plasticity, (for a review on GF interactions mediating dendritic plasticity, see [92]). We thus propose that characterizing the parallel engagement of unique families of GFs supporting learning and memory formation can yield a deeper understanding of the molecular signaling networks involved in this long-lasting and dynamic plasticity.…”