Lecture 6 - Processes Important to the Stabilization of Long-Term Potentiation Flashcards

1
Q

___ ____ in ____ ____ are key to supporting LTP

A

structural changes in dendritic spines

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1
Q

a central theory of LTP is that ____ ____ ____ increase in the ____ ____

A

AMPA receptor numbers increase in the dendritic spines

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2
Q

AMPA receptors ____ ____ and ____ of the ____

A

traffic into and out of the spines

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3
Q

AMPA receptor trafficking occurs ____ and ____ ____ ____

_____ trafficking

____-____ trafficking

A

with and without synaptic activity

constitutive trafficking

activity-induced trafficking

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4
Q

constitutive trafficking of AMPA receptors:

moves AMPA receptors ____ and ____ of the ____ _____

A

into and out of the dendritic spines

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5
Q

constitutive trafficking of AMPA receptors:

AMPA receptors are located both on the ____ and in the _____ _____ of the _____ ____

A

surface and in the intracellular space of the dendritic spine

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6
Q

constitutive trafficking of AMPA receptors:

some AMPA receptors are in the _____ and other are ______

A

PSD and others are extra synaptic

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7
Q

constitutive trafficking of AMPA receptors:

AMPA receptors are ____ by ____ in the ____ ____ and ____ back to the _____

A

captured by proteins in the endocytotic zone and recycled back to the membrane

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8
Q

constitutive trafficking of AMPA receptors:

____ processes deliver AMPA receptors to the _____ in ____ steps

A

constitutive processes deliver AMPA receptors to the membrane in 3 steps

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9
Q

constitutive processes deliver AMPA receptors to the membrane in 3 steps:

  1. _____ ____ containing ___ ____ (called ____) are ____ to ____ these ____ ____ to the region near the _____
A
  1. intracellular vesicles containing AMPA receptors (called endosomes) are mobilized to deliver theses AMPA receptors to the region near the PSD
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10
Q

constitutive processes deliver AMPA receptors to the membrane in 3 steps:

  1. these receptors then _____ ____ along the _____ to enter the ____
A

diffuse randomly along the membrane to enter the PSD

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11
Q

constitutive processes deliver AMPA receptors to the membrane in 3 steps:

  1. some receptors are _____ ____ and others ____ the ____ and are ____ back to the ____
A

trapped there and others leave the PSD and are recycled back to the endosomes

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12
Q

AMPA receptors can be composed of different _____

A

subunits

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13
Q

under resting/basal conditions, AMPA receptors tend to contain primarily _____ subunits

A

GluA2 subunits

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14
Q

LTP ____ the number of AMPA receptors with _____ subunits

A

increases the number of AMPA receptors with GluA1 subunits

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15
Q

these subunits have important ____ ____

A

phosphorylation sites

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16
Q

the initial ____ of LTP increases the number of AMPA receptors composed of _____

A

induction of LTP increases the number of AMPA receptors composed of GluA1

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17
Q

these GluA1 subunits of the AMPA receptors have ___ important ____ sites known as ____, ____, ____

A

3 important phosphorylation sites known as Ser 818, Ser 831, Ser 845

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18
Q

P1 Ser 818 ____ GluA1 to the ____

P2 Ser 831 ____ GluA1 ____ ____

P3 Ser 845 ____ GluA1 to the ____ _____

A

P1 Ser 818 anchors GluA1 to the PSD

P2 Ser 831 changes GluA1 channel conductance

P3 Ser 845 traffics GluA1 to the extrasynaptic region

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19
Q

LTP changes the ____ of AMPA receptors that are ____ or ____ in the _____

A

number of AMPA receptors that are trapped or immobilized in the PSD

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20
Q

how does LTP change the number of AMPA receptors that are trapped or immobilized in the PSD?

  • more ____ of these types of ___ ____ to the ____
  • changes to the ____ at which ____ are _____ from the ____
A
  • more capturing of these types of AMPA receptors to the PSD
  • changes to the rate at which receptors are removed from the membrane
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21
Q

the LTP ____ stimulus increases ____ of ____ _____

A

the LTP inducing stimulus increases trapping of AMPA receptors

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22
Q

how does the LTP inducing stimulus increases trapping of AMPA receptors?

3 molecules important for this:
1. ____
2. ____ known as ____
3. ___-__ ____ _____

A
  1. CaMKII
  2. TARP known as Stargazin
  3. PSD-95 scaffolding proteins
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23
Q

how do these 3 molecules interact to increase AMPA receptor number in the synapse?

  1. PSD-95 scaffolding proteins form ____ ____ for _____ AMPA receptors ____ through the _____
A
  1. PSD-95 scaffolding proteins form potential slots for trapping AMPA receptors diffusing through the PSD
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24
Q

how do these 3 molecules interact to increase AMPA receptor number in the synapse?

  1. CaMKII _____ stargazin from the _____ and facilitates ____ to _____
A
  1. CaMKII phosphorylates stargazin from the membrane and facilitates binding to PSD-95
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25
Q

how do these 3 molecules interact to increase AMPA receptor number in the synapse?

  1. the binding of ____ to ____ ____ additional AMPA receptors
A
  1. the binding of stargazin to PSD-95 traps additional AMPA receptors
26
Q

___ ____ are also important to AMPA receptor delivery to the ____

A

recycling endosomes are also important to AMPA receptor delivery to the PSD

27
Q

the initial generation of LTP causes rapid trapping of the ____ ____ ____ ____ diffusing around the _____ ____ of the plasma membrane

A

already present AMPA receptors diffusing around the extrasynaptic regions of the plasma membrane

28
Q

____ processes continue to ____ AMPA receptors from the _____

A

endocytotic processes continue to remove AMPA receptors from the PSD

29
Q

recycling endosomes contain ____ ____ ____ of AMPA receptors

___ ___ through the ____ receptors results in ____ of the _____ to the ____ ____ where these receptors can more slowly enter the ____

A

additional intracellular pools of AMPA receptors

calcium influx through the NMDA receptors results in movement of the endosomes to the extrasynaptic regions where these receptors can more slowly enter the PSD

30
Q

in terms of the increase in AMPA receptors in the PSD, calcium engages 2 independent processes:

  1. ___ ____ of ____ AMPA receptors that are ____ around the ____ ____
  2. ___ ____ of ___ ___ of AMPA receptors from the ____ to the ___ ____
A
  1. rapid trapping of existing AMPA receptors that are diffusing around the plasma membrane
  2. slower exocytosis of additional pools of AMPA receptors from the endosomes to the plasma membrane
31
Q

rapid ____ of AMPA receptors based on _____ of basal AMPA receptor ____ processes are important for LTP

A

insertion of AMPA receptors based on reorganization of basal AMPA receptor trafficking processes are important for LTP

32
Q

in order for rapid insertion of AMPA receptors based on reorganization of basal AMPA receptor trafficking processes to occur, the _____ ____ within the spine must be ____ _____

A

actin filaments within the spine must be rapidly degraded

33
Q

the influx of ____ during the ____ of LTP activates a ___ ___ that ____ the ___ ____

this is another way that ____ acts as a ___ ____ to initiate a critical step in LTP ____

A

Ca2+ during the induction of LTP activates a signaling cascade that degrades the actin cytoskeleton

Ca2+ acts as a second messenger to initiate a critical step in LTP induction

34
Q

how are LTP processes stabilized?

(___ ___) -> ____ ____ -> (____) -> ___-___ ____ -> (____) -> ___-___ ____

A

(sensory input) -> sensory memory -> (attention) -> short-term memory -> (encoding) -> long-term memory

35
Q

regarding sensory memory, ____ info is ___

A

unattended info is lost

36
Q

regarding short-term memory, ____ info is ____

A

unrehearsed info is lost

37
Q

regarding long-term memory, some info may be lost ____

A

overtime

38
Q

LTP also evolves in ____

A

stages

39
Q

delivery of ____-____ stimulus prevents ____ of ____ _____ when occurring within ____ ____ of TBS-inducing stimulus

A

low-frequency stimulus prevents development of lasting LTP when occurring within a minute of TBS-inducing stimulus

40
Q

___-___ stimulation does not prevent ____ of a _____ ____ when delivered at least ___ ___ after TBS stimulation

A

low-frequency stimulation does not prevent emergence of a durable LTP when delivered at least 10 minutes after TBS stimulation

41
Q

these finding indicate that the ____ ___ that support LTP are ___ ____ ____

but within about ___ ____, ____ ____ work to ____ these ____ ____ and ____ ____ to _____

A

synaptic changes that support LTP are not initially stable

10 minutes, additional process work to stabilize these synaptic changes and decrease vulnerability to disruption

42
Q

for LTP to endure longer that 30 minutes, ___ ___ must be ____ to create a ____ ____ ____ that will:

prevent ____ processes that ____ ____ ____ from the ____

ensure ____ of a ___ ___ of ____ ____

A

additional processes must be engaged to create a dendritic spine environment that will:

prevent endocytotic processes that will remove AMPA receptors from the PSD

ensure delivery of a steady supply of synaptic proteins

43
Q

during the 30 minute period after LTP induction, ____ ____ are recruited that change the ____ of the ____

A

additional processes are recruited that change the architecture of the spine

44
Q

during the 30 minute period after LTP induction, additional processes are recruited that change the architecture of the spine

this period is called the ____ ____ and it involves ____ of the ____ ____

A

stabilization phase and it involves remodeling of the dendritic spine

45
Q

dendritic spines have diverse ___ and ____

A

shapes and sizes

46
Q

dendritic spines are ____ and constantly ___ and ____ on _____

A

dynamic and constantly extending and retracting on dendrites

47
Q

the size of dendritic spines determines ___ ___ they will _____

larger spines ___ much ____ than small spines

A

how long they will endure

larger spines endure much longer than small spines

48
Q

dendritic spine size is highly correlated with the ____ of ___ ____ in the _____

A

number of AMPA receptors in the PSD

49
Q

these large dendritic spines can endure for ____ in living animals

A

days in living animals

50
Q

processes that create ___ ____ are critical to ____ of ____ synapses and thus key to ____ and ____

A

large spines are critical to stability of potentiated synapses and thus key to LTP and memory

51
Q

changes in dendritic spine ____, ____, and _____ underlie ___ changes due to _____

A

density, size, and plasticity underlie cognitive changes due to age

52
Q

___ ___ within spines is key to stabilizing LTP

A

actin polymerization within spines is key to stabilizing LTP

53
Q

____ is the major _____ component of dendritic spines

A

actin is the major cytoskeleton component of dendritic spines

54
Q

actin molecules exist in ____ ____: ____-actin and ___-actin

A

2 states: G-actin and F-actin

55
Q

polymerization results in the formation of a _____, which is a large molecule formed by ____ ___ ____

A

polymer, which is a large molecule formed by combining smaller molecules

56
Q

F-actin is in a constant state of ____, where it is continually ___ ____

new ____ are ____ and older ____ are ____

____ is key to this process, and thus key to ___ and ____

A

flux, where it is continually turned over

new subunits are added and older subunits are removed

cofilin is key to this process and thus key to LTP and memory

57
Q

actin exists in 2 states:

single arrow tips represent the ____ state, __-actin

strings of arrows represent ____ actin (___-actin), its ____ state

A

monomer state, G-actin

filament actin (F-actin), its polymer state

58
Q

actin is in a continuous state of ____ similar to a _____

old units are removed from the ____ end, and new units are added to the ____ end

A

turnover similar to a treadmill

old units are removed from the pointed end, and new units are added to the barbed end

59
Q

the ____ of ____ regulates actin _____

A

the state of cofilin regulates actin polymerization

60
Q

the state of cofilin regulates actin polymerization:

  1. in its normal, ____ state, cofilin ____ and _____ actin filaments
  2. when ____ by _____, ____ (____) no longer interferes with ____ ____
A
  1. in its normal, unphosphorylayted state, cofilin severs and depolymerizes actin filaments
  2. when phosphorylated by LIMK, cofilin (pcofilin) no longer interferes with actin polymerization
61
Q

actin polymerization is necessary to ____ ____

A

stabilize LTP

62
Q

when drugs (such as latrunculin and cytochalasin) that ____ ____ ____ are applied before TBS, they ___ ____ ____ the ____ of LTP, but it ___ ____ (___ is affected, not ____)

A

prevent actin polymerization are applied before TBS, they do not prevent the generation of LTP, but it rapidly decays (stability is affected, not generation)

63
Q

LTP is ____ if these drugs that prevent actin polymerization are applied ____ minutes after LTP is _____

thus, ____ ___ is necessary to ____ LTP, but not to ____ LTP

A

maintained if these drugs that prevent actin polymerization are applied 15 minutes after LTP is induced

actin polymerization is necessary to stabilize LTP, but not to generate LTP