Lecture 7: Processes Important to the Stabilization of Long-Term Potentiation Flashcards
structural changes in dendritic spines are key to ____ ____
supporting LTP
AMPA receptors are necessary for ____ ____ ____
stimulation induced LTP
induction of LTP requires an increase in ____ ____ within the ____
two ____ processes, both mediated by ____, are responsible for this
AMPA receptors within the PSD
two independent processes, both mediated by calcium, are responsible for this
actin cytoskeleton ____ is also important for the ____ / ____ phase
also mediated by ____ activation of ____ which ____ ___ the ____-___ which can prevent ____ ____ of ____ ____
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
theta burst stimulation (TBS) is a series of ____ ____ stimulation ____
it represents ____ ___ behavior in ____ while ____ ____ ___
high frequency stimulation pattern
natural electrographic behavior in rats while learning something new
in first graph, LFS is disrupting ___ ___, showing that the ____ is ____
initial potentiation, showing that the potentiation is unstable
these findings indicate that the ____ ____ that support LTP are not ____ ___
but within about ___ minutes, ____ ___ work to ____ these ___ ____ and _____ _____ to ____
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
for LTP to endure longer Thant 30 min, additional process must be engaged to create a dendritic spine environment that will:
- prevent ____ ____ that ___ ____ ___ from the ____
these processes would happen if the ___ ___ does not ____
- ensure ____ of a ____ ___ of ___ ___
allowing important ___ to ___ ___
- prevent endocytotic processes that remove AMPA receptors from the PSD
dendritic spine does not restructure
- ensure delivery of a steady supply of synaptic proteins
allowing important proteins to move in
actin polymerization within ____ are key to ____ LTP
actin polymerization within spines are key to stabilizing LTP
a major _____ component of dendritic spine is ____
cytoskeletal component of dendritic spine is actin
___ is an important protein in regulating the ____ of actin
it is considered the ___-___ step
it makes sure the _____ doesn’t _____ too much under ___ ____
cofilin is an important protein in regulating the state of actin
rate-limiting step
f-actin doesn’t polymerize too much under basal conditions
the ____ ____ of cofilin’s ____ role is essential to producing a ____ form of ____
temporary disruption of cofilin’s depolymerizing role is essential to producing a stable form of LTP
a molecule called ____ returns cofilin back to its unphosphorylated state
it ____ cofilin again
slingshot
dephosphorylates
LTP can still be _____ without ____ _____, but it is not ____
induced without actin polymerization, but it is not stable
LTP is maintained if the drugs are applied ___ minutes after LTP is ____
15 minutes after LTP is induced
actin polymerization is necessary to _____ LTP
this ____ can occur in about ____ minutes
actin polymerization is necessary to stabilize LTP
this stabilization can occur in about 15 minutes
the ____ of actin ____ is central to ___ LTP
this occurs in 2 phases: ____, ____
regulation of actin dynamics is central to stabilizing LTP
break it down, build it up
prior to LTP:
actin filaments are ____ in a ____ ____ in the ____ ____
during induction, Ca2+ ___ ___ this ___ ____
the spine neck contains _____ of ____ held together by an ____ ____ ___
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
____ and ____ of ____ activates a number of intracellular events
LTP and influx of calcium activates a number of intracellular events
phase 1 of stabilization: actin filaments are ____ and _____
unbundled and severed
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 _____
- 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
phase 2 of stabilization: the ____-____ architecture is ____
actin-spine architecture is reconstructed
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 ____-____ _____
- 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
within this 2-phase process, there is a shift in the ____ of ____ to ____….within about ___ minutes
direction of disassembling to rebuilding….within about 30 minutes
.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 ___ ____
- 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
___ ____ molecules are also important to stabilizing LTP
cell adhesion
cell adhesion molecules are ____ that are located on the ____ ____ and ____ with other ____ or with the ____ ____
proteins that are located on the cell surface and bind with other cells or with the extracellular matrix
activation of ____ ___ molecules by an ___ ___ ___ is also important for ____
activation of cell adhesion molecules by an LTP inducing stimulus is also important for stabilization
the 2 important cell adhesion molecules are _____ ____ and ____ ___ (_____)
integrin receptors and neural cadherins (N-cadherins
integrin receptors:
- connect the ____ ____ to the ____ ____
- ____ of ____ and the ____ of ____-____ ____ ____ increases the ____ of ___ ___ in the ____
- 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
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 _____ _____ ____ ____
- 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
these processes important to stabilization of LTP contribute to an _____ in ____ ____ that maintain this structure
____ size of ____
increase in large spines that maintain this structure
large size of spine
importantly, the process that ____ LTP are ____ _____ for the _____ of LTP
importantly, the process that stabilize LTP are not important for the generation of LTP
this stabilization process is ____
attempts to block stabilization are ineffective after ___ minutes
short
10 minutes
3 main phases to stabilization:
- ____-____ engaged
- rapid ____ of _____
____ ____ proteins help to ____ and ____ ____ ____ to the _____ _____ - ____-____ molecules help to maintain an ____ and ____ _____
- actin-severing engaged
- rapid polymerization of actin
actin stabilizing proteins help to crosslink and bind actin filaments to the plasma membrane - cell-adhesion molecules help to maintain an integrated and connected synapse
the construction of these ____, ____ ____ is not the only requirement for enduring LTP
large, stable spines
de novo protein synthesis hypothesis of memory:
in the _____, inhibiting ____ ____ had no impact on ____, but prevented the formation of _____ (___ work)
1960s, inhibiting protein synthesis had no impact on STM, but prevented the formation of LTM (animal work)
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 ___ ____
endure, the learning experience must result in the synthesis of new proteins
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 ____ ____
spine dynamics are impacted, there is no LTP
synaptic event is to result in an enduring LTP, then new proteins must be synthesized
the generation of new proteins is important to the ____ phase of the trace
consolidation phase of the trace
the consolidation phase of LTP is the time period during which these ____ ____ are ____
new proteins are generated
