Molecular Basis of Long-Term Memory

Question 1

What is the issue with phosphorylation of AMPA in LTP in regards to long-term memory consolidation?

Answer 1

Phosphorylation is not permanent and memory will be “erased” eventually. Proteins turnover and get degraded. We need a more permanent fix.

Question 2

How to stabilize enhanced transmission?

Answer 2

Morphological changes at synapse lead to longterm changes in synaptic strength. Need new proteins via transcription (signal to nucleus).

Question 3

Another fix for the transient effects of phosphorylation

Answer 3

Persistently active protein kinases maintain phosphorylation by AUTOPHOSPHORYLATION (no need for the activation by a second messenger). Leads to persistent phosphorylation even after Ca2+ levels drop.

Question 4

What has the ability to autophosphorylate?

Answer 4

CaMKII

Question 5

How long does autophosphorylation maintain an active form for?

Answer 5

Minutes to hours

Question 6

What is required for longer-term (days/weeks) memory consolidation?

Answer 6

Protein synthesis

Question 7

Anisomysin

Answer 7

A protein synthesis inhibitor that inhibits long-term memory consolidation

Question 8

How is a new protein formed?

Answer 8

DNA –transcription–> mRNA –translation–> protein

Question 9

Gene expression is regulated by

Answer 9

transcription factors

Question 10

What did Kandel do with anisomysin?

Answer 10

Context conditioning: 1. expose mouse to context. 2. play sound. 3. play sound and shock -> mouse freezes 4. expose mouse to context -> mouse freezes for specific duration.
Still does this 24 hours later.
Anisomycin: 5. Inject mice with anisomycin. 6. Mice still have short term memory but not long term memory -> doesn’t freeze for as long on the following day.

Question 11

Two transcription factors that are important in the consolidation of long-term memory

Answer 11

CREB-1 and CREB-2

Question 12

CREB-1

Answer 12

Activator of gene expression

Question 13

CREB-2

Answer 13

repressor of gene expression

Question 14

How do CREB-1 and CREB-2 affect gene transcription?

Answer 14

When CREB-2 is bound to specific regions of a gene, no transcription occurs.
CREB-1 and CREB-2 are competitive; CREB-1 knocks out CREB-2 and binds to gene region.
CREB-1 is phosphorylated and transcription occurs.

Question 15

What is the pathway that leads to the phosphorylation of CREB-1 and transcription?

Answer 15

NT release -> AMPA -> Na+ -> depolarization -> NMDA -> Ca2+ ->CaMK11, adenyl cyclase ->cAMP -> PKA -> phosphorylates CREB-1

Question 16

Consolidation of long-term memories depends on

Answer 16

The relative activities of CREB-1 and CREB-2. Enhanced CREB-1 facilitates the consolidation of long-term memories.

Question 17

Key requirement for LTM (days/weeks)

Answer 17

Synthesis of new proteins

Question 18

Key requirement for short-term memory (minutes/hours)

Answer 18

Autophosphorylation

Question 19

Requirement for induction of LTP?

Answer 19

Ca2+ influx

Question 20

Shorter term LTP (minutes/hours) depends on

Answer 20

AMPA insertion
AMPA phosphorylation
CaMKII autophosphorylation

Question 21

Longer term LTP depends on

Answer 21

Protein synthesis

Transcription factors