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Bear: Neuroscience: Exploring the Brain 3e Chapter 25: Molecular Mechanisms of Learning and Memory Slide 1 Neuroscience: Exploring the Brain, 3rd Ed, Bear, Connors, and Paradiso Copyright © 2007 Lippincott Williams & Wilkins Declarative memory Non-associative learning Procedual memory Associative learning Habituation Sensitization Classical conditioning Instrumental conditioning Slide 2 Neuroscience: Exploring the Brain, 3rd Ed, Bear, Connors, and Paradiso Copyright © 2007 Lippincott Williams & Wilkins Types of Memory Long-Term, Short-Term Memory Sensory information Short-term memory Consolidation Long-term memory Short-term memory Sensory information Consolidation Long-term memory Time Slide 3 Neuroscience: Exploring the Brain, 3rd Ed, Bear, Connors, and Paradiso Copyright © 2007 Lippincott Williams & Wilkins Procedural Learning Declarative and procedural memories Nonassociative Learning Habituation Learning to ignore stimulus that lacks meaning Sensitization Learning to intensify response to stimuli Slide 4 Neuroscience: Exploring the Brain, 3rd Ed, Bear, Connors, and Paradiso Copyright © 2007 Lippincott Williams & Wilkins Procedural Learning Associative Learning Classical Conditioning Slide 5 Neuroscience: Exploring the Brain, 3rd Ed, Bear, Connors, and Paradiso Copyright © 2007 Lippincott Williams & Wilkins Simple Systems: Invertebrate Models of Learning Nonassociative Learning in Aplysia (군소) Slide 6 Neuroscience: Exploring the Brain, 3rd Ed, Bear, Connors, and Paradiso Copyright © 2007 Lippincott Williams & Wilkins Simple Systems: Invertebrate Models of Learning Nonassociative Learning in Aplysia (Cont’d) Habituation of the Gill-Withdrawal Reflex Slide 7 Neuroscience: Exploring the Brain, 3rd Ed, Bear, Connors, and Paradiso Copyright © 2007 Lippincott Williams & Wilkins Habituation at the cellular level: Dr. Eric Kandel After habituation, fewer quanta per action potential were released. The sensitivity of the postsynaptic cell to NT did not change. Nonassociative Learning in Aplysia Sensitization of the Gill-Withdrawal Reflex Slide 9 How does NE accelerate the heartbeat? K+ conductance is decreased by phosphorylation modulation close If this occurs at the presynaptic nerve term., it will increase the NT release. G-protein coupled receptors (GPCR) -Same NT can have different postsynaptic actions, depending on what receptors it binds to. Ach Heart -GPCR K+ channel Hyperpolarization Slows contraction Skeletal M. -Ach-gated Na+ channel Depolarization Induce contraction Metabolic effcts Metabotropic receptors Simple Systems: Invertebrate Models of Learning Associative Learning in Aplysia Classical conditioning CS-US pairing Cellular level Molecular level Slide 14 Neuroscience: Exploring the Brain, 3rd Ed, Bear, Connors, and Paradiso Copyright © 2007 Lippincott Williams & Wilkins Simple Systems: Invertebrate Models of Learning The molecular basis for classical conditioning in Aplysia Slide 15 Neuroscience: Exploring the Brain, 3rd Ed, Bear, Connors, and Paradiso Copyright © 2007 Lippincott Williams & Wilkins Vertebrate Models of Learning Neural basis of memory learned from invertebrate studies Learning and memory can result from modifications of synaptic transmission Synaptic modifications can be triggered by conversion of neural activity into intracellular second messengers Memories can result from alterations in existing synaptic proteins Slide 16 Neuroscience: Exploring the Brain, 3rd Ed, Bear, Connors, and Paradiso Copyright © 2007 Lippincott Williams & Wilkins Pre-synaptic stimulation Post-synaptic depolarization LTP ; long-term potentiation - AMPAfication synapse split Neurons that fire together wire together (Hebb) Vertebrate Models of Learning The structure of the cerebellar cortex cortex muscle Neuroscience: Exploring the Brain, 3rd Ed, Bear, Connors, and Paradiso Copyright © 2007 Lippincott Williams & Wilkins Vertebrate Models of Learning Synaptic Plasticity in the Cerebellar Cortex Long-Term Depression in the Cerebellar Cortex Slide 20 Neuroscience: Exploring the Brain, 3rd Ed, Bear, Connors, and Paradiso Copyright © 2007 Lippincott Williams & Wilkins A mechanism of LTD induction in the cerebellum: A mechanism for motor memory? LTD is caused when three signals occur at the same time: Na+, Ca2+ and PKC Slide 22 Neuroscience: Exploring the Brain, 3rd Ed, Bear, Connors, and Paradiso Copyright © 2007 Lippincott Williams & Wilkins Vertebrate Models of Learning (declarative memory) Synaptic Plasticity in the Hippocampus Anatomy of the Hippocampus Two sheets Ammon’s horn Perforant path Vertebrate Models of Learning Synaptic Plasticity in the Hippocampus Properties of LTP in CA1 tetanus 100Hz 15-30 min Every min Input specific Vertebrate Models of Learning Synaptic Plasticity in the Hippocampus (Cont’d) Mechanisms of LTP in CA1 Glutamate receptors mediate excitatory synaptic transmission NMDARs and AMPARs PKC, CaMKII Slide 26 Neuroscience: Exploring the Brain, 3rd Ed, Bear, Connors, and Paradiso Copyright © 2007 Lippincott Williams & Wilkins Vertebrate Models of Learning Synaptic Plasticity in the Hippocampus (Cont’d) Long-Term Depression in CA1 1-5 Hz Slide 27 Neuroscience: Exploring the Brain, 3rd Ed, Bear, Connors, and Paradiso Copyright © 2007 Lippincott Williams & Wilkins Vertebrate Models of Learning LTP, LTD, and Glutamate Receptor Trafficking (Cont’d) Strongly depolarized Weakly depolarized Vertebrate Models of Learning Synaptic Plasticity in the Hippocampus LTP, LTD, and Memory - inject NMDA-receptor blocker into Hippo. water maze Susumu Tonegawa Genetic “knockout” mice Consequences of genetic deletions (e.g., CaMK11 subunit) Advances (temporal and spatial control) - Transgenic overexpressing NMDA receptor enhanced learning ability Limitations of using genetic mutants to study LTP/learning: secondary consequences Morris water maze Slide 30 Neuroscience: Exploring the Brain, 3rd Ed, Bear, Connors, and Paradiso Copyright © 2007 Lippincott Williams & Wilkins 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; 10 subunits autophosphorylation 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% New synapse