9.01 introduction to neuroscience fall 2007 for
TRANSCRIPT
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MIT OpenCourseWare http://ocw.mit.edu
9.01 Introduction to Neuroscience Fall 2007
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Declarative memory
conscious, declared, explicit
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Where is declarative memory?
epilepsy
electrical stimulation
lesion
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Temporal lobe epilepsy
• sensations • feelings of familiarity or unfamiliarity
• recollections/flashbacks • temporal cortex electrical stimulation
– causes the same effects – Wilder Penfield
• medial part of temporal lobe
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Bilateral medial temporallobectomy
Image removed due to copyright restrictions.Diagram comparing patient H.M.'s brain with normal brain.See Figure 24.8 in Bear, Mark F., Barry W. Connors, and MichaelA. Paradiso. Neuroscience: Exploring the Brain. 3rd ed. Baltimore,MD: Lippincott Williams & Wilkins, 2007.
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H.M.
• long-term memory – anterograde amnesia – partial retrograde amnesia
• short-term memory intact• procedural memory intact
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Short-term vs. long-termmemory
• Short-term memory – seconds to minutes
• Long-term memory – up to a lifetime
• Consolidation – conversion of STM to LTM
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Medial temporal lobe lesion inmonkeys
• Errors in delayed non-match to sample increase with time delay
Image removed due to copyright restrictions.See Figure 24.11 in Bear, Mark F., Barry W. Connors,and Michael A. Paradiso. Neuroscience: Exploring the Brain.3rd ed. Baltimore, MD: Lippincott Williams & Wilkins, 2007.
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Strongest effect from lesion ofperirhinal cortex
• weak effect from removal of hippocampusalone
Image removed due to copyright restrictions.See Figure 24.9b in Bear, Mark F., Barry W. Connors,and Michael A. Paradiso. Neuroscience: Exploring the Brain.3rd ed. Baltimore, MD: Lippincott Williams & Wilkins, 2007.
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Hypothesis: long-termmemories are stored bysynaptic modifications
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Hebbian synaptic plasticity
• Neurons that fire together, wire together.
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Brain slice preparation
• intracellular recording is easier than in vivo
• thickness: fraction of a millimeter • used for studying intrinsic and synaptic
conductances
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Synaptic plasticity experiment
• Measure EPSP amplitude • Induce synaptic modification • Measure new EPSP amplitude
Image removed due to copyright restrictions.See Figure 23.27a and b in Bear, Mark F., Barry W.Connors, and Michael A. Paradiso. Neuroscience:Exploring the Brain. 3rd ed. Baltimore, MD: LippincottWilliams & Wilkins, 2007.
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Long-term potentiation (LTP)
• activity-dependent synaptic modification
• lasts for tens of minutes or longer • induction
– high-frequency stimulation – postsynaptic depolarization
• found in cortex, hippocampus, etc.
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Long-term depression (LTD)
• Neurons that fire out of sync lose their link.
• induction: low-frequency stimulation
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Glutamate receptor subtypes
AMPA receptor
Postsynaptic dendritic spinePresynaptic axon terminal
Glutamate
NMDA receptor
Metabotropicglutamatereceptor
Dendrite
Axon
Figure by MIT OpenCourseWare. After Figure 23.25 in Bear, Connors, and Paradiso.Neuroscience: Exploring the Brain. 3rd ed. Baltimore, MD: Lippincott Williams &Wilkins, 2007.
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NMDA receptor
• transmitter-gated • magnesium block: voltage-gated
• permeable to calcium
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NMDA receptor as acoincidence detector
(a) Postsynaptic membrane atresting potential
(b) Postsynaptic membrane at depolarized potential
Na+ Na+Na+
Ca2+
Mg2+
Mg2+
AMPAreceptor
AMPAreceptor
NMDAreceptor
NMDAreceptor
GlutamatePresynapticglutamate
release
Presynapticglutamate
releaseGlutamate
Figure by MIT OpenCourseWare. After Figure 23.26 in Bear, Connors, and Paradiso.Neuroscience: Exploring the Brain. 3rd ed. Baltimore, MD: Lippincott Williams &Wilkins, 2007.
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The evidence
• NMDA receptor – LTP is blocked by the antagonist AP5
• Calcium – chelators (such as EGTA) block LTP – release of caged calcium mimics LTP
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Morris water maze
• swimming pool with opaque water• submerged platform • measure time for rodent to swim to
platform • learning is impaired by AP5
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NR1 knockout mouse
• NMDA-R has seven subunits • NR1 knockout is lethal. • Site-specific knockouts can be viable.
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CA3 specific NR1 knockout
• no effect on Morris water maze performance
• if visual cues are reduced, then performance suffers
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The central dogma
STM
Hebbian pattern plasticity completion
LTM
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Hebbian plasticity creates cellassemblies
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Pattern completion
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Interference
• How many memories can be stored?