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Lecture 12

PSY397H5 Lecture 12: Lecture 7 (Part I) .pdf


Department
Psychology
Course Code
PSY397H5
Professor
Robert Gerlai
Lecture
12

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11/7/11
1
THE CASE FOR GENE EXPRESSION IN L-LTP
EXPERIMENT TYPE and FINDING
Block
Block of L-LTP with protein synthesis inhibitors
Block of L-LTP with RNA synthesis inhibitors
Loss of L-LTP with CREB KOs
Block of L-LTP with Arc antisense
THE CASE FOR GENE EXPRESSION IN L-LTP
EXPERIMENT TYPE and FINDING
Measure
Increased zif268/krox24 mRNA
Increased krox20
Increased expression of fos, jun IEG mRNAs
Increased CREB phosphorylation
Increased CRE read-out
Increased elk-1 phosphorylation
Increased Arc/Arg3.1 mRNA expression
Increased AMPA receptor protein
Increased BDNF message
Increased tissue Plasminogen Activator message
Increased C/EBP beta (in long-term memory)
Increased HOMER
Increased MAP Kinase Phosphatase-1
Increased SSAT message
Increased MAP2 message
Mimic
Constitutively active CREB augments L-LTP induction
CREB Binding Protein (CBP)
cAMP Response Element
5’-TGACGTCA-3’ TATA Sequence
CREB CREB
Basal Transcription
Factor IID (TFIID)
Complex
ser 133 ser 133
RNA Helicase A
RNA
Polymerase II
Histone
pKAF
acetylation
Target
Gene
PO4 PO4
The CREB/CRE Gene Regulation System
Histone acetylation
c-fos
fosB
junB
egr-1
etc...
Histone Acetyltransferase (HAT) – Regulation of Gene Expression
Components of the LTP Gene Expression System
1. A core signal transduction cascade linking calcium to the
transcription factor CREB
2. Modulatory influences that impinge upon this cascade
3. Additional transcription factors besides CREB that may be involved
in L-LTP induction
4. Gene targets in L-LTP
5. mRNA targeting and transport
6. Effects of the gene products on synaptic structure
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