Transcript Ch 25 - Molecular Mechanisms of Learning and Memory

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