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MIT OpenCourseWare http://ocw.mit.edu 9.01 Introduction to Neuroscience Fall 2007 For information about citing these materials or our Terms of Use, visit: http://ocw.mit.edu/terms.

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Page 1: 9.01 Introduction to Neuroscience Fall 2007 For

MIT OpenCourseWare http://ocw.mit.edu

9.01 Introduction to Neuroscience Fall 2007

For information about citing these materials or our Terms of Use, visit: http://ocw.mit.edu/terms.

Page 2: 9.01 Introduction to Neuroscience Fall 2007 For

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?