Vertebrate Models of Learning

1. Vertebrate Models of Learning Synaptic Plasticity in the Hippocampus LTP and LTD Key to forming declarative memories in the brain Bliss and Lomo High frequency electrical stimulation of excitatory pathway Anatomy of Hippocampus Brain slice preparation: Study of LTD and LTP

3. Vertebrate Models of Learning Synaptic Plasticity in the Hippocampus Properties of LTP in CA1

4. LTP - hippocampus

5. LTP Form of plasticity can be induced by 1-s of tetanus LTP in CA1 in awake animals can last many weeks, maybe a lifetime. CA1 neurons must be active during tetanus for LTP Temporal & spatial summation required Important for associations

6. Vertebrate Models of Learning Synaptic Plasticity in the Hippocampus (Cont�d) Mechanisms of LTP in CA1 Glutamate receptors mediate excitatory synaptic transmission AMPARs Na+ ions enter to cause EPSP NDMARs Ca++ entry only if depolarized enough to displace Mg++ ions that clog channel Ca - PKC & CaMKII Inhibition of kinases blocks LTP More AMPARs, more spines

7. Vertebrate Models of Learning Synaptic Plasticity in the Hippocampus Long-Term Depression in CA1 (decrease synaptic effectiveness) Tetanic stimulation at low frequencies (1-5 Hz) produces LTD

8. Vertebrate Models of Learning Synaptic Plasticity in the Hippocampus (Cont�d) BCM theory Named after authors: Bienenstock, Cooper, Munro at Brown University When the postsynaptic cell is weakly depolarized by other inputs: Active synapses undergo LTD instead of LTP Accounts for bidirectional synaptic changes (up or down) LTP adding phosphate groups, LTD removing phosphate groups w protein phosphotases

9. Vertebrate Models of Learning Synaptic Plasticity in the Hippocampus (Cont�d) LTP, LTD, and Glutamate Receptor Trafficking Stable synaptic transmission: AMPA receptors are replaced maintaining the same number LTD and LTP disrupt equilibrium Bidirectional regulation of phosphorylation

10. Vertebrate Models of Learning LTP, LTD, and Glutamate Receptor Trafficking (Cont�d)

11. Vertebrate Models of Learning LTP, LTD, and Glutamate Receptor Trafficking (Cont�d) Egg carton model of AMPA receptor trafficking at synapse Size of scaffold - slot proteins Scaffold like egg carton Slot proteins form egg cups AMPARs are the eggs LTP increase scaffold LTD decrease scaffold PSD-95 may be egg carton New AMPARs have GluR1

12. The Molecular Basis of Long-Term Memory Phosphorylation as a long term mechanism: Problematic (transient and turnover rates) Persistently Active Protein Kinases Phosphorylation maintained: Kinases stay �on� CaMKII and LTP Molecular switch hypothesis

13. The Molecular Basis of Long-Term Memory Protein Synthesis Requirement of long-term memory Synthesis of new protein Protein Synthesis and Memory Consolidation Protein synthesis inhibitors Deficits in learning and memory CREB and Memory CREB: Cyclic AMP response element binding protein

14. The Molecular Basis of Long-Term Memory Protein Synthesis (Cont�d) Structural Plasticity and Memory Long-term memory associated with formation of new synapses Rat in complex environment: Shows increase in number of neuron synapses by about 25%

15. Concluding Remarks Learning and memory Occur at synapses Unique features of Ca2+ Critical for neurotransmitter secretion and muscle contraction, every form of synaptic plasticity Charge-carrying ion plus a potent second messenger Can couple electrical activity with long-term changes in brain