L3 Pharmacological Modulation of Memory

Question 1

What is memory?

Answer 1

Memory is a term given to the processes and structures involved in the storage and subsequent retrieval of information

Question 2

3 stages of memory

Answer 2

1. Encoding
2. Storage
3. Retrieval

Question 3

2 major forms of memory

Answer 3

1. Explicit (declarative) memory - conscious attention necessary for recall
2. Implicit (procedural) memory - unconsciously recalled

Question 4

How does electroshock therapy affect memory?

Answer 4

Has a serious negative impact on retrograde memory

Question 5

ADHD is believed to be due to…

Answer 5

a lack of connection between neurons in the prefrontal cortex

Question 6

Lesions to the network formed by different neuronal populations within the hippocampus affect…

Answer 6

functional connectivity and cause memory impairment

Question 7

Relay centre for memory storage

Answer 7

Hippocampus

Question 8

How was learning and memory linked to the hippocampus?

Answer 8

Patient H.M. had intractable temporal lobe epilepsy. Bilateral removal of H.M.’s temporal lobe & hippocampus cured his epileptic seizures. Declarative memory was impaired. Procedural memory was intact.

Question 9

Age-associated hippocampal atrophy corresponds to __

Answer 9

cognitive decline

Question 10

Hebb’s Rule

Answer 10

Basically cells that fire together wire together (synaptic efficacy arises from presynaptic cell repeatedly stimulating postsynaptic cell)

Question 11

A key aspect of memory is __

Answer 11

glutamate

Question 12

NMDA glutamate receptor

Answer 12

• heteromeric ion channel
• 4 subunits (2x NR1, 2x NR2)
• glutmate binds NR2
• glycine (co-agonist) binds NR1

Question 13

NMDA receptor antagonists

Answer 13

Memantine, Amantadine, Ketamine, PCP (angel dust)

Question 14

Overactivation of glutamate receptors can induce __

Answer 14

excitotoxicity

Question 15

What minerals can inhibit the NMDA receptor?

Answer 15

Zinc and magnesium

Question 16

Resting membrane potential of a neuron

Answer 16

-40mV (or low Mg2+)

Question 17

Competitive inhibitor of the active site of the NMDA receptor

Answer 17

APV

Question 18

Selective competitive AMPA receptor antagonist

Answer 18

CNQX

Question 19

What is the net result of administering APV and CNQX together?

Answer 19

no glutamate response

Question 20

What is long term potentiation?

Answer 20

A lasting, activity-dependent increase in synaptic efficacy (repeated firing of neurons strengthens synaptic connections)

Question 21

Molecular changes in LTP

Answer 21

• Glutamate activation of NMDA receptors allow Ca influx→activation of Ca/calmodulin-dependent protein kinase→phosphorylation of non-NMDA (AMPA) receptors (to increase sensitivity to glutamate)
• Repeated AP trains activate NMDA receptors, activating AC→sensitisation cascade
• Late LTP is thought to give rise to growth of new synaptic connections

Question 22

What is a potential target for novel memory enhancers, and why?

Answer 22

CREB transcription factor - transcribes genes involved in forming new synaptic connections

Question 23

NMDA antagonists in the amygdala block acquisition, but not expression, of __

Answer 23

fear learning

Question 24

What is the name given to drugs that enhance cognition (in clinical development)?

Answer 24

Nootropics

Question 25

Examples of nootropics

Answer 25

• AMPakines
• MEM1414 prolongs CREB activity (PDE inhibitor)
• GABAb receptor antagonists
• Estrogen (anabolic steroid)
• 5-HT6 receptor antagonists

Question 26

What can act as a partial agonist at the glycine site of NMDA receptors to facilitate extinction of fear memories?

Answer 26

D-cycloserine (combined with CBT)

Question 27

How does nicotine act as a cognitive enhancer?

Answer 27

• Stimulation of nAChRs leads to enhanced NT release in brain areas
• Low conc of nicotine can enhance performance in individuals with compromised nicotinic function, however, when an individual’s performance is already at optimum levels, nicotine impairs performance

Question 28

Most robust effects of nicotine are seen in tasks that have…

Answer 28

a high attentional requirement

Question 29

Increased smoking in patients with…

Answer 29

ADHD and schizophrenia

Question 30

Sensorimotor gating inhibition deficit in schizophrenia has been linked to __

Answer 30

nAChα7 subunit gene (reduced number in hippocampus of patients)

Question 31

What are in development for improving cognitive symptoms of schizophrenia?

Answer 31

α7-nicotinic agonists

Question 32

Examples of pharmacological agents that can regulate PFC function

Answer 32

• D1 receptor agonist (A77636) - improves (low dose) and impairs (high dose) working memory in monkey
• Guanfacine (agonist at postsynaptic α2A-adrenoceptors) - improves working memory in WT mice, but no benefit in α2A-KO mice

Question 33

Most effective treatments for ADHD facilitate…

Answer 33

catecholamine transmission

Question 34

Drug treatments for ADHD

Answer 34

• Methylphenidate (Ritalin) - blocks DA & NA transporters (approved)
• Amphetamines (e.g. Adderall) - block DA & NA transporters (approved)
• Atomoxetine (inhibits NA transporters)
• Guanfacine (NA mimetic)

Question 35

Methylphenidate improves performance of…

Answer 35

PFC tasks

Question 36

Attention enhancer than inhibits DAT

Answer 36

Modafinil (approved drug treatment for individuals with attention deficit)

Question 37

What is caffeine?

Answer 37

An adenosine receptor antagonist that interacts with GABAergic and dopaminergic neurotransmission

Question 38

Potential MCI therapeutics

Answer 38

• AChE inhibitors
• Anti-oxidants
• Anti-inflammatories
• Glu receptor modulators
• Nootropics
• Immunomodulators

Question 39

True or False: Environmental effects modify learning

Answer 39

True