1. By: Dustin Horn

2. Synaptic Plasticity During Learning
Overview of a Neuron
Short Term
Early Long Term Potentiation
Late Long Term Potentiation
The “Synaptic Tag”

3. The Neuron

4. Function

5. Other Terms Receptors: NMDA and AMPA
Glutamate receptors with integrated ion channels
Plasticity: change within the synapses that results in new electrical properties
Cytoskeleton: Actin
fibers within the cell
Allow transport
Support cell shape

6. Short Term Happen on timescale of seconds
Actin dependent post-synaptic plasticity

8. 10 % change in shape could significantly change synaptic communication
Possible mechanism:
Actin polymerization affects NMDA receptor
NMDA receptor affects actin polymerization

9. Early Long Term Potentiation
Changes properties of existing cellular processes
Proteins move to new locations
Proteins are chemically altered
Lasts for hours
NMDA and AMPA receptors

10. AMPA and NMDA

11. Late Long-Term Potentiation
Requires protein synthesis
FMRP- Fragile-x Mental Retardation Protein binds to mRNA

12. Unlocking of mRNA Local Glutamate receptors are activated
Results in phosphorylation of FMRP
Frees mRNA
Local synaptic ribosomes translate proteins

13. ARC/PSD-95 Located in the post-synaptic density
Regulates # of glutamate receptors inserted into plasma membrane

14. BDNF -Brain-Derived Neurotrophic Factor
Autocrine signal that regulates:
Scaffold Proteins
Neuro-transmitter Receptors
Inactive synapse elimination

15. “Synaptic Tag” Experiment Proposal
mRNA molecules are guided to proper location by a “Synaptic Tag”
Transcription in Nucleus
Loaded into vesicles
Transported along cytoskeleton
Molecular Identity is Unknown
Hypothesis:
Protein attached to FMRP or CAMKII
What and where?

16. Tracking Vesicular Movement

17. Magnetic Immuno-Precipitation

18. Gel-Electrophoresis & Mass Spec.

19. Gene Knock Out
CRISPR/Cas-9
Transgenic GFP-ARC

20. Immuno-Gold SEM Develop anti-bodies against candidate protein
Add in gold particle-antibody complex
Use SEM to locate protein

21. In Conclusion Neuronal synapses are dynamic structures
Changes last from seconds to weeks
Modulation of synapses underlies our ability to learn
Not all molecules involved in the processes are known
Synaptic “tag” is an important molecule in ability to form long-term memory

22. Questions?

23. References
Slides 2-5: Levitan, I. The Neuron: Cell and Molecular Biology. Oxford Univeristy Press Ch 1-4
Slides 6-8:Rapid Actin-Based Plasticity in Dendritic Spines. Fischer, Maria et al.Neuron , Volume 20 , Issue 5 ,
Slides 9-14: Levitan, I. The Neuron: Cell and Molecular Biology. Oxford Univeristy Press Ch 11, 17, 19
15-16: Ralf Dahm, Manuel Zeitelhofer, Bernhard Götze, Michael A. Kiebler, Paolo Macchi, Visualizing mRNA Localization and Local Protein Translation in Neurons, Methods in Cell Biology, Academic Press, 2008, Volume 85, Pages
Slides 15-20: Cox, M. Molecular Biology: Principles and Practice. W.H. Freeman and company. New York

24. Pictures Slides 2,6-8: Figures from
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20: Figure from: