Lecture 6 Part II

Question 1

memory is measured by the stability of ?

Answer 1

• behaviors
• synaptic connections
• cell morphology
• neuronal function

Question 2

ways biomolecules turn over occurs rapidly in neurons

Answer 2

• phosphorylation events
• transmembrane receptors
• majority of proteins
• even actin microfilaments

Question 3

T or F: A single phosphorylation event, synthesized protein, inserted ion channel, synaptic contact cannot store memory for an appreciable amount of time

Answer 3

true

Question 4

Paradigms for studying behavioral memory and memory impairment

Answer 4

• Habituation
• dishabituation
• sensitization
• fear conditioning (cued vs contextual)
• spatial learning

Question 5

Fear conditioning

Answer 5

• puts animal in box
• pair particular context with foot shock and auditory cue
• when we put animal back into this particular context the animal will freeze
• when we put animal into a different context animal shows less freezing way
• context -only or auditory-only
• context-only memory is hippocampal dependent

Question 6

modeling memory disorders: Alzheimer’s disease

Answer 6

• Alzheimer’s is characterized by an impairment in declarative memory formation
• extracellular B-amyloid protein plaque formation and intracellular neurofibrillary tangles composed of tau protein

-accompanied by neuroinflammation of nearby glial cells and neuronal loss in the hippocampus, cortex, and other brain regions

Question 7

which paradigms of learning are simple and non-associative btw multiple cues

Answer 7

• habituation
• dishabituation
• sensitization

Question 8

which paradigms of learning are associative

Answer 8

• fear conditioning

- spatial learning

Question 9

Most common method use to studying learning

Answer 9

fear conditioning

Question 10

the _________ memory in the fear conditioning paradigm is hippocampal dependent while the _______ memory is not

Answer 10

context-only; auditory -only

Question 11

how is studying the mechanisms that underline contextual hippocampal dependent types of memories help in understanding disorders like Alzheimer’s?

Answer 11

-some of the mechanisms being studied that underline contextual hippocampal dependent types of memories are also present and involve in what becomes dysregulated during cognitive disorders like Alzheimer’s

• Use freezing model as a way of studying learning but also as a way of understanding
  a. what becomes dysregulated
  b. By purposely dysregulating something can we induced contextual memory deficits
  c. Can we treat animals and restored/ see a revival in contextual memory

Question 12

dysregulation of Cdk5 in neurodegenerative diseases occurs under what conditions

Answer 12

-cyclin dependent kinase

Question 13

CDK5

Answer 13

• early development (neuronal migration)
• synaptic plasticity
• synaptic structure
• axon guidance
• memory transport/ formation
• microtubule stability /transport

Question 14

Cdk5 dysregulation is linked to some of the pathologies associated with what

Answer 14

-Alzheimer’s disease

Question 15

Cdk5 dysregulation occurs under what conditions

Answer 15

-neurotoxic conditions in which its regulatory protein p35 is cleaved to generated a p25 molecule

Question 16

To investigate whether Cdk5 dyregulation is associated with neurodegeneration what type of model is needed

Answer 16

conditional transgenic mouse model

Question 17

p25

Answer 17

• contributes to the B-amyloid plaque buildup associated with Alzheimer’s disease
• ends up producing excessive phosphorylation of the protein

Question 18

If we wanted to understand Cdk5 and how its dysregulation impacts a neurodegenerative disorder it will be really important to control Cdk5 spatially and temporally in relevant ways . which method would we use and why

Answer 18

• a mouse model in which Cdk5 becomes dysregulated in old age that way we can understand what p25 causes and to test treatments
• b/c during birth Cdk5 dysregulation will cause much more problems so we wouldn’t be able to test and measure

Question 19

two strategies used to genetically engineer mice

Answer 19

• targeted insertion of trans genes (engineered genes)

- ectopic insertion of transgene (random)

Question 20

transgenic mouse models

Answer 20

-knockout / knock-in

• used to understand the function of a gene
• Knock-in: what happens when the gene is in the wrong place or expressed at the wrong time (gain of function)

-knockout: what happens when the gene is gone (loss of function)

Question 21

which newer transgenic models allow for highly specific spatial and temporal manipulation of gene expression, which is used to address numerous questions

Answer 21

• Cre-lox

- TetO

Question 22

conditional transgenic mouse models

Answer 22

-

Question 23

Tetracycline Inducible Systems

Answer 23

• used to dysregulate during old age
• tetracycline activator protein is borrowed from bacterial system
• something mammalian cells would not normally be able to generate
• insert sequences into the gene that can be controlled into a specific promoter
• when tetracycline transactivator protein is expressed we use it by building a TetO promoter to control the activity of a second gene

Question 24

what process involves something getting expressed under specific conditions and then used to regulate the expression of a second gene

Answer 24

tetracycline inducible systems

Question 25

tetracycline inducible systems pathway

Answer 25

insert sequences into specific promoter ---> tetracycline transactivation protein expressed---> binds to TetO promoter which allows ---> controlling of second gene X

Question 26

Doxycycline

Answer 26

- an antibiotic drug - when administered it prevents the Tetracycline transactivator protein from binding to the TetO promoter -the drug will control the timing of when your transgene gets activated Ex: insert sequence that produces p25 into mice during embryo, insert doxycycline in order to prevent expression , mice grow up fine, take off doxycycline once mice are old, p25 gets expressed we can test it

Question 27

Synaptic plasticity hypothesis

Answer 27

- nerve cells are interconnected in fixed patterns, yet presumably undergo some sort of change when we learn or remember - if the connections between cells are so precise, what could that change be

Question 28

if the connections between cells are so precise, what allows for these patterns of activity to change across time

Answer 28

- learning was mediated by changes in synaptic connections - the strength of synaptic connections - the ease with which an action potential in one cell excites (or inhibits) its target cell- is not fixed but plastic and modifiable

Question 29

Hebb's postulate

Answer 29

- neurons that fire together wire together - when an axon of cell A is near enough to excite a cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic changes takes place in one or both cells such that A's efficiency as one of the cells firing B, is increased

Question 30

pyramidal cells

Answer 30

- long term potentiation | - connect to facilitate memory formation

Question 31

when cell A fires persistently and repeatedly onto cell B its easier for cell A to fire cell B in the future, there is a potentiation . this is defining

Answer 31

Hebb's postulate

Question 32

inducing and measuring plasticity steps

Answer 32

- stimulated cell A ---> recorded a particular postsynaptic potential in cell B ---> then use high frequency stimulation (repeat trial constantly) ---> record second time ---> we see that when we give the same stimulus that was given initially we get much larger response - what we think is happening on the molecular processes as the animal is learning - response that we get the second time to the same stimulus is amplified

Question 33

NMDA receptor are a ____ and _______ receptor subtype

Answer 33

ligand; voltage-gated glutamate

Question 34

NMDA receptors are activated and open calcium channels only under two which conditions

Answer 34

- glutamate has to be released from the pre-synaptic neuron and BINDING (NEUROTRANSMITTER BINDING) to glutamate needs to occur. - the post-synaptic membrane has to be DEPOLARIZED in order to remove the magnesium block from NMDA.

Question 35

____ receptors are necessary for long term potentiation because they allow for an influx of ____ into the cell which is critical for LTP

Answer 35

NMDA ; CALCIUM

Question 36

how does the membrane become depolarized enough for NMDA to be activated

Answer 36

- glutamate is released and binds to NMDA and AMPA - AMPA opens NA+ channels - enough NA+ inside causes depolarization ---> ejecting the Magnesium plug -NMDA allow NA+ and Calcium to enter

Question 37

calcium enters the cell and activates the _____ mechanisms that strengthen the synapse

Answer 37

intracellular

Question 38

early LTP is likely subserved by persistently activated _____

Answer 38

protein kinases

Question 39

late LTP requires _____ and new _____

Answer 39

gene transcription ; new protein synthesis