Memory II
• Learning is the acquisition of new information   – Classical Conditioning• Memory is the retention of learned information
Electrical vs. Synaptic Storage of Memory• Anesthesia• Electroshock therapy• Protein Synthesis Inhibitors
The Hebbian Synapse“When an Axon of Cell A is near enough to excite a cell BAnd repeatedly or persistently takes part in f...
Strong Activity        In „A‟ Leads to1       Action Potentials        In „D‟23    4
Weak Activity        In „B‟ or „C‟1       Leads to        Nothing In „D‟23    4
Strong Activity        In „A‟ Leads1       Paired with        Weak activity in        „B” leads to        Action Potential...
Strengthening of the        B to D connection1         • Cooperativity &           Associativity2        • Input specifici...
Such a system might beAble to produce Classical Conditioning       Conditioned       Stimulus       (eg Tone) Unconditione...
How Synapses Might Change
More        More      Bothtransmitter receptorsreleased
Searching for the Hebbian Synapse          Hippocampus
Bliss and Lomo
LTP (Long-Term Potentiation)Is a long term change in synaptic strength            Hippocampal LTP requires NMDA receptors
NMDAr – Coincident Detector                   To Open…                   - Depolarization to                       remove ...
Neural Basis of LTP in theHippocampus  • Silent synapse
Neural Basis of LTP in theHippocampus                         Influx in Ca through                         NMDAr causes   ...
Neural Basis of LTP in theHippocampus term changes…          Long
Calcium Influx can alsoLead to even morePermanent changesLike the formation ofNew synapses
LTP PhasesLTP 1 (less than 3hours)   -blocked by NMDA blockers   -blocked by protein kinase inhibitorsLTP 2   -blocked by ...
Are Phases of LTP related to Short- and Long-Term Memory?                   long        intermediateshort                 ...
Is NMDA mediated LTP really the         Neural basis of memory?• Blocking NMDA receptors often blocks learning• Increase i...
Doogie MouseIncreased number of NMDA receptors
Morris Water Maze
Anti-NMDA-receptor Autoimmune Ancephalitis                   Josep Dalmau M.D. Ph.D.                   University of Penns...
BCM Theory• Accounts for bi-direction of synaptic  strength• „Neurons that fire together wire  together‟… AND „neurons tha...
HippocampalLong Term Depression              - Low frequency                stimulation              - Low Ca influx      ...
Cerebellar Long Term                   DepressionDifferences…- Inhibitory output- NMDAr independent- mGluR (parallel fiber...
Lecture19 memory ii
Lecture19 memory ii
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Lecture19 memory ii

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Lecture19 memory ii

  1. 1. Memory II
  2. 2. • Learning is the acquisition of new information – Classical Conditioning• Memory is the retention of learned information
  3. 3. Electrical vs. Synaptic Storage of Memory• Anesthesia• Electroshock therapy• Protein Synthesis Inhibitors
  4. 4. The Hebbian Synapse“When an Axon of Cell A is near enough to excite a cell BAnd repeatedly or persistently takes part in firing it a growthProcess of metabolic change takes place in one or both cellsSuch that A‟s efficacy, as one of the cells firing B, is increased.
  5. 5. Strong Activity In „A‟ Leads to1 Action Potentials In „D‟23 4
  6. 6. Weak Activity In „B‟ or „C‟1 Leads to Nothing In „D‟23 4
  7. 7. Strong Activity In „A‟ Leads1 Paired with Weak activity in „B” leads to Action Potentials2 In „D‟ AND...3 4
  8. 8. Strengthening of the B to D connection1 • Cooperativity & Associativity2 • Input specificity3 4
  9. 9. Such a system might beAble to produce Classical Conditioning Conditioned Stimulus (eg Tone) Unconditioned Unconditioned Stimulus Response (eg Meat) (eg Salivation)
  10. 10. How Synapses Might Change
  11. 11. More More Bothtransmitter receptorsreleased
  12. 12. Searching for the Hebbian Synapse Hippocampus
  13. 13. Bliss and Lomo
  14. 14. LTP (Long-Term Potentiation)Is a long term change in synaptic strength Hippocampal LTP requires NMDA receptors
  15. 15. NMDAr – Coincident Detector To Open… - Depolarization to remove Mg plug - Glutamate Binding Lets both Na & Ca pass through
  16. 16. Neural Basis of LTP in theHippocampus • Silent synapse
  17. 17. Neural Basis of LTP in theHippocampus Influx in Ca through NMDAr causes AMPAr insertion („un-silencing‟) into the postsynaptic membrane leading to a stronger synapse!
  18. 18. Neural Basis of LTP in theHippocampus term changes… Long
  19. 19. Calcium Influx can alsoLead to even morePermanent changesLike the formation ofNew synapses
  20. 20. LTP PhasesLTP 1 (less than 3hours) -blocked by NMDA blockers -blocked by protein kinase inhibitorsLTP 2 -blocked by gene translation inhibitors -blocked by protein synthesis inhibitorsLTP 3 (days) -requires extensive synaptic remodeling -requires transcription & translation
  21. 21. Are Phases of LTP related to Short- and Long-Term Memory? long intermediateshort Chick learned avoidance behavior
  22. 22. Is NMDA mediated LTP really the Neural basis of memory?• Blocking NMDA receptors often blocks learning• Increase in AMPAr of rats that were trained in inhibitory avoidan• Disrupting genes involved in LTP disrupts learning
  23. 23. Doogie MouseIncreased number of NMDA receptors
  24. 24. Morris Water Maze
  25. 25. Anti-NMDA-receptor Autoimmune Ancephalitis Josep Dalmau M.D. Ph.D. University of Pennsylvania Discovered 2007 NYU’s Souhel Najjar M.D. An illness now thought to be the cause of “demonic possessions” throughout history
  26. 26. BCM Theory• Accounts for bi-direction of synaptic strength• „Neurons that fire together wire together‟… AND „neurons that fire out of sync, loose their link‟
  27. 27. HippocampalLong Term Depression - Low frequency stimulation - Low Ca influx - Activation of phosphatases - AMPAr internalization
  28. 28. Cerebellar Long Term DepressionDifferences…- Inhibitory output- NMDAr independent- mGluR (parallel fiber)- VGCC (climbing fiber)- Requires kinases for depression not potentiationSimilarities…- AMPAr internalization

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