vertebrate models of learning synaptic plasticity in the hippocampus –ltp and ltd key to forming...
TRANSCRIPT
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
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
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.
LTP - hippocampus
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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
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
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
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
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
Vertebrate Models of Learning
• LTP, LTD, and Glutamate Receptor Trafficking (Cont’d)
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
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
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
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%
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