9.01 Introduction to Neuroscience Fall 2007
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1 MIT OpenCourseWare Introduction to Neuroscience Fall 2007 For information about citing these materials or our Terms of Use, visit:
2 Declarative memory conscious, declared, explicit
3 Where is declarative memory? epilepsy electrical stimulation lesion
4 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
5 Bilateral medial temporal lobectomy 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 Michael A. Paradiso. Neuroscience: Exploring the Brain. 3rd ed. Baltimore, MD: Lippincott Williams & Wilkins, 2007.
6 H.M. long-term memory anterograde amnesia partial retrograde amnesia short-term memory intact procedural memory intact
7 Short-term vs. long-term memory Short-term memory seconds to minutes Long-term memory up to a lifetime Consolidation conversion of STM to LTM
8 Medial temporal lobe lesion in monkeys Errors in delayed non-match to sample increase with time delay Image removed due to copyright restrictions. See Figure in Bear, Mark F., Barry W. Connors, and Michael A. Paradiso. Neuroscience: Exploring the Brain. 3rd ed. Baltimore, MD: Lippincott Williams & Wilkins, 2007.
9 Strongest effect from lesion of perirhinal cortex 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, weak effect from removal of hippocampus alone
10 Hypothesis: long-term memories are stored by synaptic modifications
11 Hebbian synaptic plasticity Neurons that fire together, wire together.
12 Brain slice preparation intracellular recording is easier than in vivo thickness: fraction of a millimeter used for studying intrinsic and synaptic conductances
13 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: Lippincott Williams & Wilkins, 2007.
14 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.
15 Long-term depression (LTD) Neurons that fire out of sync lose their link. induction: low-frequency stimulation
16 Glutamate receptor subtypes Presynaptic axon terminal Postsynaptic dendritic spine Glutamate Dendrite AMPA receptor Axon NMDA receptor Metabotropic glutamate receptor Figure by MIT OpenCourseWare. After Figure in Bear, Connors, and Paradiso. Neuroscience: Exploring the Brain. 3rd ed. Baltimore, MD: Lippincott Williams & Wilkins, 2007.
17 NMDA receptor transmitter-gated magnesium block: voltage-gated permeable to calcium
18 NMDA receptor as a coincidence detector (a) Postsynaptic membrane at resting potential (b) Postsynaptic membrane at depolarized potential Presynaptic glutamate release Mg 2+ Glutamate Presynaptic glutamate release Glutamate Mg 2+ AMPA receptor NMDA receptor AMPA receptor NMDA receptor Ca 2+ Na + Na + Na + Figure by MIT OpenCourseWare. After Figure in Bear, Connors, and Paradiso. Neuroscience: Exploring the Brain. 3rd ed. Baltimore, MD: Lippincott Williams & Wilkins, 2007.
19 The evidence NMDA receptor LTP is blocked by the antagonist AP5 Calcium chelators (such as EGTA) block LTP release of caged calcium mimics LTP
20 Morris water maze swimming pool with opaque water submerged platform measure time for rodent to swim to platform learning is impaired by AP5
21 NR1 knockout mouse NMDA-R has seven subunits NR1 knockout is lethal. Site-specific knockouts can be viable.
22 CA3 specific NR1 knockout no effect on Morris water maze performance if visual cues are reduced, then performance suffers
23 The central dogma STM Hebbian plasticity pattern completion LTM
24 Hebbian plasticity creates cell assemblies
25 Pattern completion
26 Interference How many memories can be stored?
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