title: De Novo synthesis of CREB in a presynaptic neuron is required for synaptic enhancement involved in memory consolidation.
abstract: Interaction between the activator type of cyclic AMP response element binding protein (CREB1) and the repressor type (CREB2) results in determining the emergence of long-lasting synaptic enhancement involved in memory consolidation. However, we still do not know whether the constitutively expressed forms of CREB are enough or the newly synthesized forms are required for the synaptic enhancement. In addition, if the newly synthesized forms are needed, we must determine the time for translation of CREB from its mRNA. We applied the methods of RNA interference and real-time polymerase chain reaction (PCR) to CREB in the cerebral giant cells of Lymnaea. The cerebral giant cells play an important role in associative learning and employ a CREB cascade for the synaptic enhancement to neurons such as the B1 motoneurons. We injected the small interfering RNA (siRNA) of CREB1 or CREB2 into the cerebral giant cells and examined the changes in amplitude of excitatory postsynaptic potential (EPSP) recorded in the B1 motoneurons. The changes in the amounts of CREB1 and CREB2 mRNAs were also examined in the cerebral giant cells. The EPSP amplitude was suppressed 15 min after injection of CREB1 siRNA, whereas that was augmented 60 min after injection of CREB2 siRNA. In the latter case, the decrease in the amount of CREB2 mRNA was confirmed by real-time PCR. Our results showed that the de novo synthesized forms of CREB are required within tens of minutes for the synaptic enhancement in memory consolidation.
authors.affiliation: Division of Biological Sciences, Graduate School of Science, Hokkaido University, Sapporo, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Wagatsuma
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Azami
authors.forename: Midori
authors.initials: M
authors.lastname: Sakura
authors.forename: Dai
authors.initials: D
authors.lastname: Hatakeyama
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Aonuma
authors.forename: Etsuro
authors.initials: E
authors.lastname: Ito
mesh_terms: D000818:Animals; D050882:CREB-Binding Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002490:Central Nervous System / Q000166:cytology; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000528:radiation effects; D015870:Gene Expression / Q000187:drug effects; D066298:In Vitro Techniques; D008195:Lymnaea; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D050882:CREB-Binding Protein