Lecture 7: Processes Important to the Stabilization of Long-Term Potentiation

Question 1

structural changes in dendritic spines are key to ____ ____

Answer 1

supporting LTP

Question 2

AMPA receptors are necessary for ____ ____ ____

Answer 2

stimulation induced LTP

Question 3

induction of LTP requires an increase in ____ ____ within the ____

two ____ processes, both mediated by ____, are responsible for this

Answer 3

AMPA receptors within the PSD

two independent processes, both mediated by calcium, are responsible for this

Question 4

actin cytoskeleton ____ is also important for the ____ / ____ phase

also mediated by ____ activation of ____ which ____ ___ the ____-___ which can prevent ____ ____ of ____ ____

Answer 4

actin cytoskeleton degradation is also important for the generation or induction phase

Ca2+ activation of calpains which break down the actin-mesh which can prevent rapid insertion of AMPA receptors

Question 5

theta burst stimulation (TBS) is a series of ____ ____ stimulation ____

it represents ____ ___ behavior in ____ while ____ ____ ___

Answer 5

high frequency stimulation pattern

natural electrographic behavior in rats while learning something new

Question 6

in first graph, LFS is disrupting ___ ___, showing that the ____ is ____

Answer 6

initial potentiation, showing that the potentiation is unstable

Question 7

these findings indicate that the ____ ____ that support LTP are not ____ ___

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

Answer 7

synaptic changes that support LTP are not initially stable

but within about 10 minutes, additional processes work to stabilize these synaptic changes and decrease vulnerability to disruption

Question 8

for LTP to endure longer Thant 30 min, additional process must be engaged to create a dendritic spine environment that will:

1. prevent ____ ____ that ___ ____ ___ from the ____

these processes would happen if the ___ ___ does not ____

2. ensure ____ of a ____ ___ of ___ ___

allowing important ___ to ___ ___

Answer 8

1. prevent endocytotic processes that remove AMPA receptors from the PSD

dendritic spine does not restructure

2. ensure delivery of a steady supply of synaptic proteins

allowing important proteins to move in

Question 9

actin polymerization within ____ are key to ____ LTP

Answer 9

actin polymerization within spines are key to stabilizing LTP

Question 10

a major _____ component of dendritic spine is ____

Answer 10

cytoskeletal component of dendritic spine is actin

Question 11

___ is an important protein in regulating the ____ of actin

it is considered the ___-___ step

it makes sure the _____ doesn’t _____ too much under ___ ____

Answer 11

cofilin is an important protein in regulating the state of actin

rate-limiting step

f-actin doesn’t polymerize too much under basal conditions

Question 12

the ____ ____ of cofilin’s ____ role is essential to producing a ____ form of ____

Answer 12

temporary disruption of cofilin’s depolymerizing role is essential to producing a stable form of LTP

Question 13

a molecule called ____ returns cofilin back to its unphosphorylated state

it ____ cofilin again

Answer 13

slingshot

dephosphorylates

Question 14

LTP can still be _____ without ____ _____, but it is not ____

Answer 14

induced without actin polymerization, but it is not stable

Question 15

LTP is maintained if the drugs are applied ___ minutes after LTP is ____

Answer 15

15 minutes after LTP is induced

Question 16

actin polymerization is necessary to _____ LTP

this ____ can occur in about ____ minutes

Answer 16

actin polymerization is necessary to stabilize LTP

this stabilization can occur in about 15 minutes

Question 17

the ____ of actin ____ is central to ___ LTP

this occurs in 2 phases: ____, ____

Answer 17

regulation of actin dynamics is central to stabilizing LTP

break it down, build it up

Question 18

prior to LTP:

actin filaments are ____ in a ____ ____ in the ____ ____

during induction, Ca2+ ___ ___ this ___ ____

the spine neck contains _____ of ____ held together by an ____ ____ ___

Answer 18

connected in a meshlike network in the spine head

breaks apart this meshlike network

bundles of F-actin held together by an inactive CaMKII complex

Question 19

____ and ____ of ____ activates a number of intracellular events

Answer 19

LTP and influx of calcium activates a number of intracellular events

Question 20

phase 1 of stabilization: actin filaments are ____ and _____

Answer 20

unbundled and severed

Question 21

phase 1 of stabilization:

• _____ is activated / ____ from ____, exposing these filaments to _____ that ____ the ____ _____ ____ into ____ ____
• ____ moves into the ____ region and _____ _____ and prevents them from ____ / other forces also increase ____ of ____ ___ and increase ____ ____ of _____

Answer 21

• CaMKII is activated / detaches from F-actin, exposing these filaments to proteins that sever the long F-actin strands into shorter strands
• cofilin moves into the spine region and depolymerizes F-actin and prevents them from rejoining / other forces also increase shearing of actin bundles and increase smaller strands of F-actin

Question 22

phase 2 of stabilization: the ____-____ architecture is ____

Answer 22

actin-spine architecture is reconstructed

Question 23

phase 2 of stabilization:

• ____ is ____ and can no longer ____ ____
• other enzymes also ____ the ____/____ of actin
• these new, small ____ strands are ____ ____
• although ____ will soon dephosphorylate ____, other proteins _____ these new ____ and ____ them from ____-____ _____

Answer 23

• cofilin is phosphorylated and can no longer depolymerize actin
• other enzymes also terminate the severing/depolymerization of actin
• these new, small f-actin strands are rapidly polymerized
• although slingshot will soon dephosphorylate cofilin, other proteins reorganize these new strands and protect them from cofilin-initated depolymerization

Question 24

within this 2-phase process, there is a shift in the ____ of ____ to ____….within about ___ minutes

Answer 24

direction of disassembling to rebuilding….within about 30 minutes

Question 25

.cofilin has a central role in this stabilization process: - the active, _____ state of cofilin is important in phase ____ - phosphorylation of cofilin is necessary to generate an ____ and ____ ___ ___ in the ___ ____

Answer 25

- the active, unphosphorylated state of cofilin is important in phase 1 - phosphorylation of cofilin is necessary to generate an expanded and enduring actin environment in the dendritic spine

Question 26

___ ____ molecules are also important to stabilizing LTP

Answer 26

cell adhesion

Question 27

cell adhesion molecules are ____ that are located on the ____ ____ and ____ with other ____ or with the ____ ____

Answer 27

proteins that are located on the cell surface and bind with other cells or with the extracellular matrix

Question 28

activation of ____ ___ molecules by an ___ ___ ___ is also important for ____

Answer 28

activation of cell adhesion molecules by an LTP inducing stimulus is also important for stabilization

Question 29

the 2 important cell adhesion molecules are _____ ____ and ____ ___ (_____)

Answer 29

integrin receptors and neural cadherins (N-cadherins

Question 30

integrin receptors: - connect the ____ ____ to the ____ ____ - ____ of ____ and the ____ of ____-____ ____ ____ increases the ____ of ___ ___ in the ____

Answer 30

- connect the extracellular matrix to the actin cytoskeleton - influx of Ca2+ and the activation of calcium-induced signaling cascades increases the number of integrin molecules in the PSD

Question 31

neural cadherins (n-cadherins): - facilitate the ____ of ___ and _____ regions - with an increase in synaptic activity, they begin to ____ ____ and help to keep the ____ and ____ regions of these _____ _____ ____ ____

Answer 31

- facilitate the coupling of pre and postsynaptic regions - with an increase in synaptic activity, they begin to cluster together and help to keep the presynaptic and postsynaptic regions of these larger spines tightly coupled

Question 32

these processes important to stabilization of LTP contribute to an _____ in ____ ____ that maintain this structure ____ size of ____

Answer 32

increase in large spines that maintain this structure large size of spine

Question 33

importantly, the process that ____ LTP are ____ _____ for the _____ of LTP

Answer 33

importantly, the process that stabilize LTP are not important for the generation of LTP

Question 34

this stabilization process is ____ attempts to block stabilization are ineffective after ___ minutes

Answer 34

short 10 minutes

Question 35

3 main phases to stabilization: 1. ____-____ engaged 2. rapid ____ of _____ ____ ____ proteins help to ____ and ____ ____ ____ to the _____ _____ 3. ____-____ molecules help to maintain an ____ and ____ _____

Answer 35

1. actin-severing engaged 2. rapid polymerization of actin actin stabilizing proteins help to crosslink and bind actin filaments to the plasma membrane 3. cell-adhesion molecules help to maintain an integrated and connected synapse

Question 36

the construction of these ____, ____ ____ is not the only requirement for enduring LTP

Answer 36

large, stable spines

Question 37

de novo protein synthesis hypothesis of memory: in the _____, inhibiting ____ ____ had no impact on ____, but prevented the formation of _____ (___ work)

Answer 37

1960s, inhibiting protein synthesis had no impact on STM, but prevented the formation of LTM (animal work)

Question 38

de novo protein synthesis hypothesis of memory: 1960s, inhibiting protein synthesis had no impact on STM, but prevented the formation of LTM (animal work) thus, this hypothesis suggests that for memories to _____, the learning experience must result in the _____ of ___ ____

Answer 38

endure, the learning experience must result in the synthesis of new proteins

Question 39

de novo protein synthesis hypothesis of memory: LTP research came later and provided overwhelming evidence that if ____ ____ are impacted, there is no ____ BUT there is evidence that if a ___ ____ is to result in an ____ ____, then ____ ____

Answer 39

spine dynamics are impacted, there is no LTP synaptic event is to result in an enduring LTP, then new proteins must be synthesized

Question 40

the generation of new proteins is important to the ____ phase of the trace

Answer 40

consolidation phase of the trace

Question 41

the consolidation phase of LTP is the time period during which these ____ ____ are ____

Answer 41

new proteins are generated