2. • Learning is the acquisition of new information
– Classical Conditioning
• Memory is the retention of learned information
3. Electrical vs. Synaptic Storage of Memory
• Anesthesia
• Electroshock therapy
• Protein Synthesis Inhibitors
4. The Hebbian Synapse
“When an Axon of Cell A is near enough to excite a cell B
And repeatedly or persistently takes part in firing it a growth
Process of metabolic change takes place in one or both cells
Such that A‟s efficacy, as one of the cells firing B, is increased.
5. Strong Activity
In „A‟ Leads to
1 Action Potentials
In „D‟
2
3
4
6. Weak Activity
In „B‟ or „C‟
1 Leads to
Nothing In „D‟
2
3
4
7. Strong Activity
In „A‟ Leads
1 Paired with
Weak activity in
„B” leads to
Action Potentials
2 In „D‟ AND...
3
4
8. Strengthening of the
B to D connection
1
• Cooperativity &
Associativity
2 • Input specificity
3
4
9. Such a system might be
Able to produce Classical Conditioning
Conditioned
Stimulus
(eg Tone)
Unconditioned Unconditioned
Stimulus Response
(eg Meat) (eg Salivation)
17. Neural Basis of LTP in the
Hippocampus
Influx in Ca through
NMDAr causes
AMPAr insertion
(„un-silencing‟) into
the postsynaptic
membrane leading
to a stronger
synapse!
19. Calcium Influx can also
Lead to even more
Permanent changes
Like the formation of
New synapses
20.
21. LTP Phases
LTP 1 (less than 3hours)
-blocked by NMDA blockers
-blocked by protein kinase inhibitors
LTP 2
-blocked by gene translation inhibitors
-blocked by protein synthesis inhibitors
LTP 3 (days)
-requires extensive synaptic remodeling
-requires transcription & translation
22. Are Phases of LTP related to
Short- and Long-Term Memory?
long
intermediate
short Chick learned avoidance
behavior
23. 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
26. 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
27. 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‟
28. Hippocampal
Long Term Depression
- Low frequency
stimulation
- Low Ca influx
- Activation of
phosphatases
- AMPAr
internalization
29. Cerebellar Long Term
Depression
Differences…
- Inhibitory output
- NMDAr independent
- mGluR (parallel fiber)
- VGCC (climbing fiber)
- Requires kinases for depression
not potentiation
Similarities…
- AMPAr internalization
