title: Transforming growth factor β recruits persistent MAPK signaling to regulate long-term memory consolidation in Aplysia californica.
abstract: In this study, we explore the mechanistic relationship between growth factor signaling and kinase activity that supports the protein synthesis-dependent phase of long-term memory (LTM) consolidation for sensitization ofAplysia Specifically, we examine LTM for tail shock-induced sensitization of the tail-elicited siphon withdrawal (T-SW) reflex, a form of memory that requires both (i) extracellular signal-regulated kinase (ERK1/2; MAPK) activity within identified sensory neurons (SNs) that mediate the T-SW and (ii) the activation of transforming growth factor β (TGFβ) signaling. We now report that repeated tail shocks that induce intermediate-term (ITM) and LTM for sensitization, also induce a sustained post-training phase of MAPK activity in SNs (lasting at least 1 h). We identified two mechanistically distinct phases of post-training MAPK: (i) an immediate phase that does not require ongoing protein synthesis or TGFβ signaling, and (ii) a sustained phase that requires both protein synthesis and extracellular TGFβ signaling. We find that LTM consolidation requires sustained MAPK, and is disrupted by inhibitors of protein synthesis and TGFβ signaling during the consolidation window. These results provide strong evidence that TGFβ signaling sustains MAPK activity as an essential mechanistic step for LTM consolidation.
authors.affiliation: Department of Neurobiology, University of California at Los Angeles, Los Angeles, California 90095, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Shobe
authors.affiliation: Center for Neural Science, New York University, New York, New York 10003, USA.
authors.forename: Gary T
authors.initials: GT
authors.lastname: Philips
authors.affiliation: Center for Neural Science, New York University, New York, New York 10003, USA tcarew@nyu.edu.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Carew
mesh_terms: D000818:Animals; D001048:Aplysia; D003609:Dactinomycin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017952:Ganglia, Invertebrate / Q000166:cytology; D066298:In Vitro Techniques; D057567:Memory, Long-Term / Q000187:drug effects / Q000502:physiology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D008954:Models, Biological; D010446:Peptide Fragments / Q000494:pharmacology; D010812:Physical Stimulation; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D018709:Statistics, Nonparametric; D013623:Tail / Q000294:innervation; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D016212:Transforming Growth Factor beta; D003609:Dactinomycin; D020929:Mitogen-Activated Protein Kinase Kinases