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

2. Vertebrate Models of Learning
Synaptic Plasticity in the Hippocampus
Anatomy of the Hippocampus
Hippocampus:
Dentate Gyrus
Ammon’s horn (4 divisions: CA1, CA2, CA3, CA4; (CA stands for cornu Ammonis, Latin for “Ammon’s horn.”
Perforant path
Mossy fibers
Schaffer collateral

3. Vertebrate Models of Learning
Synaptic Plasticity in the Hippocampus
Properties of LTP in CA1
LTP first shown in perforant path synapses on CA3 neurons; now in Schaffer collateral synapse on CA1 neurons.
Test stimulus versus tetanus, a brief burst of high-frequency stimulation.
LTP is input specific.

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 Unique features of Ca2+
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