Gene expression profiling of facilitated L-LTP in VP16-CREB mice reveals that BDNF is critical for the maintenance of LTP and its synaptic capture.
Expression of VP16-CREB, a constitutively active form of CREB, in hippocampal neurons of the CA1 region lowers the threshold for eliciting the late, persistent phase of long-term potentiation (L-LTP) in the Schaffer collateral pathway. This VP16-CREB-mediated L-LTP differs from the conventional late phase of LTP in not being dependent on new transcription. This finding suggests that in the transgenic mice the mRNA transcript(s) encoding the protein(s) necessary for this form of L-LTP might already be present in CA1 neurons in the basal condition. We used high-density oligonucleotide arrays to identify the mRNAs differentially expressed in the hippocampus of transgenic and wild-type mice. We then explored the contribution of the most prominent candidate genes revealed by our screening, namely prodynorphin, BDNF, and MHC class I molecules, to the facilitated LTP of VP16-CREB mice. We found that the overexpression of brain-derived neurotrophic factor accounts for an important component of this phenotype.
Barco
Angel
A
Center for Neurobiology and Behavior, Columbia University, 1051 Riverside Drive, New York, New York 10032, USA. abarco@umh.es
Patterson
Susan L
SL
Patterson
Susan
S
Alarcon
Juan M
JM
Gromova
Petra
P
Mata-Roig
Manuel
M
Morozov
Alexei
A
Kandel
Eric R
ER
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000172:deficiency / Q000502:physiology*; D050882:CREB-Binding Protein / Q000172:deficiency / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D005091:Exons; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D017405:Herpes Simplex Virus Protein Vmw65 / Q000172:deficiency / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology; D017403:In Situ Hybridization / Q000379:methods; D017774:Long-Term Potentiation / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009473:Neuronal Plasticity / Q000235:genetics*; D009474:Neurons / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013569:Synapses / Q000235:genetics*; D009435:Synaptic Transmission; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D017405:Herpes Simplex Virus Protein Vmw65; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse