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

• DOI: 10.1016/j.neuron.2015.04.025
• Publication Date: 2015-06-03T15:50:24Z
• Authors: Ashley M. Kopec; Gary T. Philips; Thomas J. Carew
• Keywords: 0301 basic medicine; Membrane Glycoproteins; Memory, Long-Term; Time Factors; Neuroscience(all); Intracellular Space; Receptor, Transforming Growth Factor-beta Type II; Protein Serine-Threonine Kinases; Protein-Tyrosine Kinases; Transforming Growth Factor beta2; 03 medical and health sciences; Organ Culture Techniques; Aplysia; Animals; Intercellular Signaling Peptides and Proteins; Receptor, trkB; Receptors, Transforming Growth Factor beta; Signal Transduction

Several growth factors (GFs) have been implicated in long-term memory (LTM), but no single GF can support all of the plastic changes that occur during memory formation. Because GFs engage highly convergent signaling cascades that often mediate similar functional outcomes, the relative contribution of any particular GF to LTM is difficult to ascertain. To explore this question, we determined the unique contribution of distinct GF families (signaling via TrkB and TGF-βr-II) to LTM formation in Aplysia. We demonstrate that TrkB and TGF-βr-II signaling are differentially recruited during two-trial training in both time (by trial 1 or 2, respectively) and space (in distinct subcellular compartments). These GFs independently regulate MAPK activation and synergistically regulate gene expression. We also show that trial 1 TrkB and trial 2 TGF-βr-II signaling are required for LTM formation. These data support the view that GFs engaged in LTM formation are interactive components of a complex molecular network.