Lecture 4-Learning and Memory Continued

Question 1

long-term depression (LTD)

Answer 1

Form of long-term synaptic plasticity decreases synaptic strength?

Question 2

What Long-Term Depression (LTD) is typically induced by?

Answer 2

low-frequency stimulation,

Question 3

What cellular changes occur during long-term depression (LTD) in the hippocampus?

Answer 3

Low Calcium Rise: When there’s a small increase in calcium (Ca2+) in the postsynaptic CA1 neuron, it’s the trigger.

Protein Phosphatases Activate: The low calcium activates proteins called protein phosphatases within the neuron.

AMPA Receptor Internalization: These protein phosphatases cause AMPA receptors in the postsynaptic neuron to move inside the cell.

Moving AMPA receptors inside makes the neuron less responsive to glutamate from the Schaffer collateral terminals.

Question 4

What are the key requirements for long-term depression (LTD) to occur in the brain?

Answer 4

LTD requires depolarization of the Purkinje cell (caused by climbing fiber activation) and signals generated by active parallel fiber synapses.

Question 5

What happens to the strength of parallel fiber signals during LTD?

Answer 5

Pairing stimulation of climbing fibers (CF) and parallel fibers (PF) causes LTD, which reduces the strength of the parallel fiber EPSP (excitatory postsynaptic potential).

Question 6

Long-term potentiation (LTP)

Answer 6

Strengthens synaptic connections

Question 7

What is LTP caused by?

Answer 7

Stimulate the neurons with a high frequency stimulus,

Question 8

LTP involved the _____ of AMPA recpetors?

Answer 8

LTP involves the addition of AMPA receptors to the neuron’s surface, which makes it more sensitive to signals.

Question 9

LTD involves the ____ of AMPA receptors

Answer 9

It involves removal of AMPA receptors from the neuron’s surface, reducing its sensitivity to signals.

Question 10

Describe the role of the enzyme CaMKII in synaptic plasticity, specifically in long-term potentiation (LTP) and long-term depression (LTD)

Answer 10

1) CaMKII acts as a crucial enzyme in both LTP and LTD.
2) Upon calcium influx through channels, calcium binds to calmodulin, changing its shape and activating CaMKII through phosphorylation.
3) Phosphorylation of CaMKII subunits encodes the strength of synaptic activation.
4) Once phosphorylated, CaMKII can enter the nucleus and initiate pathways that activate CREB.
5) CREB is a DNA-binding protein that can trigger the transcription of many genes related to learning and memory.

Question 11

What triggers the activation of CaMKII in synaptic plasticity?

Answer 11

The influx of calcium into the neuron and its binding to calmodulin triggers the activation and subsequent phosphorylation of CaMKII.

Question 12

How does CaMKII contribute to encoding synaptic strength?

Answer 12

CaMKII has multiple phosphorylation sites on its subunits, with more calcium influx leading to stronger phosphorylation, reflecting the level of synaptic activity.

Question 13

What is the correlation between calcium influx and CaMKII phosphorylation?

Answer 13

There is a direct correlation between the amount of calcium influx and the degree of phosphorylation on CaMKII, with more influx resulting in stronger phosphorylation

Question 14

What role does phosphorylated CaMKII play in gene expression?

Answer 14

Phosphorylated CaMKII can enter the nucleus and interact with CREB to activate transcriptional pathways involved in learning and memory

Question 15

What is the effect of LTP-inducing stimuli on CaMKII activation?

Answer 15

LTP-inducing stimuli, like 100 Hz stimulation, result in maximal phosphorylation and activation of CaMKII, strengthening synaptic responses.

Question 16

How does LTD-inducing stimulation affect CaMKII?

Answer 16

LTD-inducing stimulation, such as 1 Hz, leads to a different pattern of CaMKII phosphorylation, which reduces its activity and weakens synaptic connections.

Question 17

What determines the different states of CaMKII activation?

Answer 17

The activation state of CaMKII is determined by the site and extent of its phosphorylation, which can be influenced by the frequency of synaptic stimuli.

Question 18

What determines CaMKII’s presence in dendritic spines?

Answer 18

CaMKII’s integration or removal from spines is governed by phosphorylation levels: high for LTP means it stays in the spine, strengthening connections, while less during LTD means it leaves, weakening connections.

Question 19

What is the role of CREB in synaptic plasticity?

Answer 19

CREB is a DNA-binding protein that can either inhibit or promote gene transcription, depending on its form (CREB1 or CREB2), playing a crucial role in long-term synaptic plasticity.

Question 20

How does CREB2 regulate gene expression?

Answer 20

CREB2 binds to the CRE site on DNA and inhibits gene transcription, preventing the expression of genes involved in synaptic plasticity.

Question 21

What is the consequence of CREB1 phosphorylation?

Answer 21

Phosphorylation of CREB1 activates it, resulting in the transcription of genes that contribute to the molecular changes underlying long-term memory.

Question 22

What activates gene transcription in the CREB pathway?

Answer 22

Strong neural signals cause CREB1 to swap with CREB2 and get phosphorylated, turning on gene transcription.

Question 23

What can be the consequence of using protein synthesis inhibitors in memory experiments?

Answer 23

r] Protein synthesis inhibitors can lead to deficits in learning and memory by preventing the consolidation phase of long-term memory formation.

Question 24

Why is protein synthesis critical in the formation of long-term memory?

Answer 24

Protein synthesis is essential for long-term memory because it supports the structural and functional changes needed at synapses for memory consolidation.

Question 25

How does CREB contribute to both LTP and LTD?

Answer 25

CREB is a transcription factor that, when activated, can initiate the synthesis of proteins necessary for both LTP and LTD, thereby influencing synaptic strength and plasticity

Question 26

What does the fact that LTD can occur without being affected by protein synthesis inhibitors suggest?

Answer 26

It suggests that not all forms of synaptic plasticity are dependent on new protein synthesis and that LTD might rely on different molecular mechanisms.

Question 27

What is the role of FMRP in synaptic plasticity?

Answer 27

FMRP is an RNA-binding protein essential for translating mRNA into proteins that regulate the activity of glutamate receptors, such as AMPA receptors, crucial for synaptic plasticity.