BIPN 148 Lecture 15

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BIPN 148 Lecture 15
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Calcium regulation of gene expression
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Spatial learning defects in dnCKIV mice
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Impaired hippocampal LTP in CKIV null mice
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Impaired amygdala and cortical LTP in CKIV null
mice
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Impaired fear conditioning in CKIV null mice
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Calcium regulation of gene expression
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Reduced CREB phosphorylation in CKIV null mice
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Reduced CREB phosphorylation in CKIV null mice
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Reduced CREB phosphorylation in fear conditioning
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Fear conditioning induces CRE-mediated gene
expression
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Reduced Fear Conditioning after inhibition of CREB
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Transcriptional targets of CREB
CaMKIV ERK
RSK2
Elk-1
CBP/CREB
zif268
CRE
SRE
C/EBP
krox20
Arc
AMPAR HOMER BDNF (Brain-derived Neurotrophic
Factor) NT-3
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BDNF increases synaptic efficacy
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Reduction in LTP in BDNF null mice
Kandel et al.
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Rescue of LTP defect by infusion of BDNF
Kandel et al.
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Reduced LTP in conditional TrkB (BDNF receptor)
null mice
Klein et al.
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Impaired spatial learning in BDNF mutants
WT
BDNF mutant
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Synaptic Tagging and LTP
New gene products or proteins
New gene products or proteins
Synaptic tag
NMDAR
Signal to nucleus
Synaptic Potentiation
Locally generated tag captures new gene product
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CREB and taste aversion
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THE CASE FOR GENE EXPRESSION IN L-LTP
EXPERIMENT TYPE and FINDING Block Block of
L-LTP with protein/RNA synthesis
inhibitors  Block of L-LTP with RNA synthesis
inhibitors  Loss of L-LTP with CREB KOs Block of
L-LTP with Arc antisense  Loss of L-LTP with
CaMKIV KO  Loss of L-LTP with zif268 KO  
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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 (Brain-derived
neurotrophic factor) message