Lecture 6 Part II Flashcards Preview

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1

memory is measured by the stability of ?

-behaviors
-synaptic connections
-cell morphology
-neuronal function

2

ways biomolecules turn over occurs rapidly in neurons

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

3

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

true

4

Paradigms for studying behavioral memory and memory impairment

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

5

Fear conditioning

-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

6

modeling memory disorders: Alzheimer's disease

-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

7

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

-habituation
-dishabituation
-sensitization

8

which paradigms of learning are associative

-fear conditioning
-spatial learning

9

Most common method use to studying learning

fear conditioning

10

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

context-only; auditory -only

11

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

-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

12

dysregulation of Cdk5 in neurodegenerative diseases occurs under what conditions

-cyclin dependent kinase

13

CDK5

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

14

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

-Alzheimer's disease

15

Cdk5 dysregulation occurs under what conditions

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

16

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

conditional transgenic mouse model

17

p25

-contributes to the B-amyloid plaque buildup associated with Alzheimer's disease

-ends up producing excessive phosphorylation of the protein

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

- 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

19

two strategies used to genetically engineer mice

-targeted insertion of trans genes (engineered genes)

-ectopic insertion of transgene (random)

20

transgenic mouse models

-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)

21

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

-Cre-lox
-TetO

22

conditional transgenic mouse models

-

23

Tetracycline Inducible Systems

-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

24

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

tetracycline inducible systems

25

tetracycline inducible systems pathway

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

26

Doxycycline

-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

27

Synaptic plasticity hypothesis

-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

28

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

-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

29

Hebb's postulate

-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

30

pyramidal cells

-long term potentiation
-connect to facilitate memory formation