MCDB 4777/5777
Molecular Neurobiology
Lecture 17
Mechanisms of Synaptic Plasticity and Learning
Learning Goals for Lecture 17
2.4 Understand mechanisms by which patterns of neuronal activity can lead to synaptic
plasticity
a. Distinguish between mechanisms that increase and decrease synaptic strength
(habituation, sensitization, LTP, LTD).
b. Relate intracellular signal transduction mechanisms to modification of neuronal
excitability properties.
Goals for today…
The neuromuscular junction- a synapse that can change with prior
activity
Aplysia and a primitive form of learning- habituation and sensitization
The hippocampus and its requirement for spatial learning and memory
Hippocampal circuitry and long-term potentiation of synaptic strengthdefinition
Requirements for LTP- association and timing
Figure 8.2 Short-term plasticity at the neuromuscular synapse (Part 1)
24.1 Short-term sensitization of the Aplysia gill withdrawal reflex. (Part 1)
24.1 Short-term sensitization of the Aplysia gill withdrawal reflex. (Part 2)
Lecture 17
What mechanism would you predict
causes this serotonin-mediated
short-term sensitization of the Aplysia
gill withdrawal circuit, in the time
frame observed?
A. a change in gene transcription
B. a change in mRNA translation
C. a change in posttranslational modification
D. a change in ion concentration gradients
24.2 Synaptic mechanisms underlying short-term sensitization. (Part 1)
24.2 Synaptic mechanisms underlying short-term sensitization. (Part 2)
Habituation- due to synaptic
depression- fewer vesicles for
release
Behavioral Sensitization- serotonin
from modulatory interneuron
enhances transmitter releasesynaptic facilitation
Lecture 17
What kind of posttranslational modification
would most likely cause the effect seen here
after shocking the tail in Aplysia?
A. phosphorylation of Ca2+ channels, reducing the chance they will open
during a depolarization
B. phosphorylation of K+ channels, reducing the chance they will open during
a depolarization
C. phosphorylation of metabotropic serotonin receptors, reducing their
activation of G-protein
D. Transcription, translation, and insertion of additional voltage-gated calcium
channels
Additional InfoAll synapses shown are excitatory
Modulatory interneuron- uses serotonin
As an excitatory transmitter
24.3 Mechanism of presynaptic enhancement underlying behavioral sensitization. (Part 1)
Mechanisms of short-term Sensitization- serotonin from modulatory interneuron enhances transmitter
release
Lecture 17
What mechanism would you predict
causes this serotonin-mediated
long-term sensitization of the Aplysia
gill withdrawal circuit, in the time
frame observed?
A. a change in gene transcription
B. a change in mRNA translation
C. a change in posttranslational modification
D. a change in ion concentration gradients
24.3 Mechanism of presynaptic enhancement underlying behavioral sensitization. (Part 2)
Long-term Sensitization- increased degradation of PKA regulatory subunit; PKA constitutive
Also- C/EBP causes creation of additional synapses
Box A Genetics of Learning and Memory in the Fruit Fly
Dunce- cAMP phosphodiesterase
Rutabaga- adenylyl cyclase
Amnesiac-peptide transmitter
stimulating adenylyl cyclase
Manipulation of CREB also interferes
w/ learning & memory in flies
The rodent hippocampus
30.7 Spatial learning and memory in rodents depends on the hippocampus. (Part 1)
Testing spatial learning and memory in rodents
30.7 Spatial learning and memory in rodents depends on the hippocampus. (Part 2)
24.5 Diagram of a section through the rodent hippocampus.
Lecture 17, CQ 1
What happens to pathway 1 after high
frequency stimulation?
A.
there is a higher frequency of
action potentials
B.  More pathways are activated,
including pathway 2
C. There must be more transmitter
released or a more responsive
postsynaptic membrane
D.  The Schaeffer collaterals increase
in number
E.  All of the above
Figure 8.7 Long-term potentiation of Schaffer collateral-CA1 synapses
Figure 8.7 Long-term potentiation of Schaffer collateral-CA1 synapses (Part 1)
Figure 8.7 Long-term potentiation of Schaffer collateral-CA1 synapses (Part 2)
Figure 8.7 Long-term potentiation of Schaffer collateral-CA1 synapses (Part 3)
24.7 Pairing presynaptic and postsynaptic activity causes LTP. (Part 1)
+depolarize!
24.7 Pairing presynaptic and postsynaptic activity causes LTP. (Part 2)
LTP is state-dependentpairing of a weak stimulus
(that wouldn t cause LTP) w/
depolarization (w/in ~100ms)
leads to LTP