1. BIPN 148 Lecture 15

2. Calcium regulation of gene expression

3. Spatial learning defects in dnCKIV mice

4. Impaired hippocampal LTP in CKIV null mice

5. Impaired amygdala and cortical LTP in CKIV null mice

6. Impaired fear conditioning in CKIV null mice

7. Calcium regulation of gene expression

8. Reduced CREB phosphorylation in CKIV null mice

10. Reduced CREB phosphorylation in fear conditioning

11. Fear conditioning induces CRE-mediated gene expression

12. Reduced Fear Conditioning after inhibition of CREB

13. CRESRE zif268 C/EBP krox20 AMPAR HOMER BDNF (Brain-derived Neurotrophic Factor) NT-3 Arc CBP/CREB CaMKIV + ERK Elk-1 RSK2 Transcriptional targets of CREB

14. BDNF increases synaptic efficacy

15. Reduction in LTP in BDNF null mice Kandel et al.

16. Rescue of LTP defect by infusion of BDNF Kandel et al.

17. Reduced LTP in conditional TrkB (BDNF receptor) null mice Klein et al.

18. Impaired spatial learning in BDNF mutants WTBDNF mutant

19. New gene products or proteins Signal to nucleus New gene products or proteins Synaptic Potentiation Locally generated tag captures new gene product Synaptic tag NMDAR Synaptic Tagging and LTP

20. CREB and taste aversion

21. 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

22. 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