Exam 2 3/30/16
14
Exam 1
12
Range: 60-100
Average: 79.8
10
# students
Exam 1 2/17/16
Range: 49-98
Average: 77
Exam 2
8
6
4
2
0
A (90-100)
B (80-89)
C (70-79)
D (60-69)
F (<60)
Per student performance comparison exam 1 vs. 2
100
90
Exam 2 grade
80
70
60
50
40
40
50
60
70
Exam 1 grade
80
90
100
The four basic stages of neurotransmission
The generation & release of a synaptic vesicle
Synaptic vesicles are recycled following exocytosis
From action potential to postsynaptic depolarization
Action potential via Na+ channels depolarizes the presynaptic
cell to open PSM Ca2+ channels & promote vesicle fusion
AMPA-R: Na+/K+ channel; NMDA-R: Ca2+ channel
NMDA-R required for postsynaptic depolarization
Remember: the NMJ synapse requires ACh - AChR
Both presynaptic and postsynaptic factors influence release
probability
# docked vesicles (pre) + active Rs (post)
# release sites (pre) + active Rs (post)
# active Rs & # spines (post) contacting AZ (pre)
Habituation vs. sensitization to repeated stimulus
Habituation:
mild stimulus
Sensitization:
noxious
stimulus
Aplysia as a model for learning and memory
Eric Kandel
Aplysia protects itself from potential harm by withdrawing its gill
when the siphon is touched
40 sensory neurons (siphon skin) synapse w/ 6 gill MNs &
excitatory and inhibitory INs
Electrophysiology in Aplysia using the abdominal ganglia
Habituation was observed in Aplysia by EPSP recordings after
repeated siphon stimulation
Possible mechanisms for short-term habituation
Habituation leads to decreased neurotransmitter release and
reduced gill withdrawal
Long-term habituation after 4 days of training synaptic
depression & fewer sensorimotor synapses
A strong aversive stimulus leads to enhanced neurotransmission
via facilitatory INs  amplified signal to MNs = sensitization
Sensitization/short-term memory involves 5-HT, cAMP, & PKA
All 3 increase
Glu release
Increased MN response (EPSPs) after injecting 5-HT, cAMP, or
PKA
5-min incubation with 5-HT causes cAMP increase (pre) +
EPSP (post) = cAMP facilitates sensitization
Ionotropic Rs (eg. AMPA): ion channel; GABAB-R, 5HTR:
metabotropic R
Decreased K+ via PKA phosphorylation prolongs action potential
normal
action
potential
after
sensitization
1) 5-HT binds R;
AdCyc ON
2) cAMP turns PKA
ON
3) PKA phos. K+
channel– closed
4) action potential
keeps Ca2+
channels open
PKA also acts directly on neurotransmitter release machinery
Presynaptic facilitation targets K+ channels, NT vesicles, & Ca2+
channels
Repetitive shocks for 4 days induces shock memory for 2-3 weeks
= LTM
Catalytic subunits of PKA translocate from the cytoplasm to the
nucleus
RNA polymerase needs direct contact w/ enhancer binding
proteins to activate transcription
CREB-2 represses transcription; CREB-1 displaces it to activate
Sensitizing stimulus in tail results in heightened responses at the
synapse & in behavior
stimulating the tail then
the siphon increased
response in gill with
drawal
requires interneuron
release of 5HT 
increased cAMP 
increased PKA 
enhanced NT release
Long-term LTP: MAPK, CREB transcription/short-term LTP: 5HT,
cAMP increases, activating PKA, closing K+ chan & incr NT release
Learning to pair stimulus with reward: classical conditioning
Classical conditioning in Aplysia: pairing tail shock with water jet
on the siphon; output= gill withdrawal reflex
US
CS
US/CS: unconditional/conditional stimulus
Mechanism: activation of interneurons via CS increases Ca2+ to
enhance response to stimulus (activation of Ca2+-dep AdCyc)
Training and neuronal circuits in learning in Aplysia
siphon
5HT neuron (tail)
Conditioning: APCa2+ influx calmodulin  cAMP  PKA
increased NT release
Presynaptic depolarization by INs increases Glu release to amplify
PSP response
Figure 21-53. Intracellular signaling pathways during
sensitization and classical conditioning in the Aplysia
gill-withdrawal reflex arc. Sensitization occurs when the
facilitator neuron is triggered by the unconditioned
stimulus (US) in the absence of the conditioned
stimulus (CS) to the siphon sensory neuron (see Figure
21-52). Classical conditioning occurs when the CS is
applied 1 – 2 seconds before the US, and involves
coincidence detectors in both the presynaptic siphon
sensory neuron and the motor neuron. In the sensory
neuron, the detector is an adenylate cyclase that is
activated by both Ca2+-calmodulin and by Gsα· GTP
(see Figure 21-42). In the motor neuron, the detectors
are NMDA glutamate receptors (see Figure 21-40).
Partial depolarization of the motor neuron induced by
an unconditioned stimulus (via an unknown transmitter)
from interneurons activated by the tail sensory neuron
enhances the response to glutamate released by the
siphon sensory neuron.
Learning & memory w/ odor + shock in Drosophila melanogaster
Genetic mutants in Drosophila that identified memory pathways
amnesiac: enhances AdCyc; dPACAP=
pituitary AdCyc activating peptide
Ddc: Dopamine
decarboxylase
rutabaga: defective
Ca2+-calmod dep.
AdCyc
dunce: PDE mutation