Lecture 38: Cellular Basis of Learning and Memory

Question 1

What is the molecular mechanism underlying short-term sensitization?

Answer 1

1. Serotonin is released from interneurons and bind to GPCRs on the terminal bouton of the sensory neuron
   
   • hence why Hamilton called it a serotenergic axoaxonal mediated process
2. activated G-protein makes cAMP which is eventually converted into PROTEIN KINASE A
3. For short-term shit, elevation of PKA in terminal bouton leads to increased Ca influx/neurotramitter release

Question 2

What is the molecular mechanism for long-term sensitization?

Answer 2

Serotonin from interneurons leads to PKA in terminal bouton
In this case, however, PKA travels in a retrograde fashion and PHOSPHORYLATES CREB
Phosphorylation of CREB thereby activates CRE which leads to transcription of more genes that lead to increased synaptical activity
That’s why it is said that long-term sensitization involves a STRUCTURAL change

Question 3

Most well studied pathway in hippocampus? Significance?

Answer 3

1. Perforant path from entorhinal cortex synapses with mossy fibers of dentate gyrus
2. Mossy fibers then go to CA3 pyramidal cells (Shaffer collaterals)
3. Schaffer collaterals then go to CA1 (output)
   If you stimulate this guy, it is shown that this pathway demonstrates long-term potentiation

Question 4

Schaffer collaterals

Answer 4

CA3 pyramidal cells = hippocampus

Question 5

What are the neurotransmitters used in learning? What type of receptors are associated with them?

Answer 5

Glutamate

AMPA and NMDA

Question 6

What is long-term potentiation? Molecular change?

Answer 6

Long-lasting enhancement in signal transmission between two neurons that results from stimulating them synchronously
Significance: one cellular mechanism that underlies learning and memory
Example: sensitization
More AMPA-receptors

Question 7

What are the four properties of long term potentiation?

Answer 7

A. Rapid onset
B. Long-lasting
C. Pathway (synapse) specificity
-specific to synapses of the stimulated input
D. Associativity
-results from PAIRING of postsynaptic depolarization with presynaptic activity
-NMDA mediated

Question 8

What is long-term depression? Molecular change?

Answer 8

Activity-dependent reduction in the efficacy of neuronal synapses lasting hours following long patterned stimulus
Significance: also a cellular mechanism for learning
Example: habituation
Less AMPA

Question 9

What is the significance of NMDA? What are its properties?

Answer 9

NMDA is a glutamate receptor on postsynaptic membrane
Activated ONLY when depolarized
-so NMDA can sense a concomitant depolarization of pre-synaptic membrane and post-synaptic membrane when there is a high-frequency of synaptic ctivation
Significance: NMDA is a coincidence detector and a logical choice for associative learning
-allows for LTP because postsynaptic terminal has greater response to glutamate (since NMDA receptors now open along with AMPA)

Question 10

What is single trial, short term memory dependent upon?

Answer 10

Phosphorylation

Question 11

What is multiple long term memory dependent upon?

Answer 11

Translation and Transcription

Can involve structural change

Question 12

Where can learning and memory be expressed?

Answer 12

At the synaptic level