Lecture 6 - Processes Important to the Stabilization of Long-Term Potentiation Flashcards
___ ____ in ____ ____ are key to supporting LTP
structural changes in dendritic spines
a central theory of LTP is that ____ ____ ____ increase in the ____ ____
AMPA receptor numbers increase in the dendritic spines
AMPA receptors ____ ____ and ____ of the ____
traffic into and out of the spines
AMPA receptor trafficking occurs ____ and ____ ____ ____
_____ trafficking
____-____ trafficking
with and without synaptic activity
constitutive trafficking
activity-induced trafficking
constitutive trafficking of AMPA receptors:
moves AMPA receptors ____ and ____ of the ____ _____
into and out of the dendritic spines
constitutive trafficking of AMPA receptors:
AMPA receptors are located both on the ____ and in the _____ _____ of the _____ ____
surface and in the intracellular space of the dendritic spine
constitutive trafficking of AMPA receptors:
some AMPA receptors are in the _____ and other are ______
PSD and others are extra synaptic
constitutive trafficking of AMPA receptors:
AMPA receptors are ____ by ____ in the ____ ____ and ____ back to the _____
captured by proteins in the endocytotic zone and recycled back to the membrane
constitutive trafficking of AMPA receptors:
____ processes deliver AMPA receptors to the _____ in ____ steps
constitutive processes deliver AMPA receptors to the membrane in 3 steps
constitutive processes deliver AMPA receptors to the membrane in 3 steps:
- _____ ____ containing ___ ____ (called ____) are ____ to ____ these ____ ____ to the region near the _____
- intracellular vesicles containing AMPA receptors (called endosomes) are mobilized to deliver theses AMPA receptors to the region near the PSD
constitutive processes deliver AMPA receptors to the membrane in 3 steps:
- these receptors then _____ ____ along the _____ to enter the ____
diffuse randomly along the membrane to enter the PSD
constitutive processes deliver AMPA receptors to the membrane in 3 steps:
- some receptors are _____ ____ and others ____ the ____ and are ____ back to the ____
trapped there and others leave the PSD and are recycled back to the endosomes
AMPA receptors can be composed of different _____
subunits
under resting/basal conditions, AMPA receptors tend to contain primarily _____ subunits
GluA2 subunits
LTP ____ the number of AMPA receptors with _____ subunits
increases the number of AMPA receptors with GluA1 subunits
these subunits have important ____ ____
phosphorylation sites
the initial ____ of LTP increases the number of AMPA receptors composed of _____
induction of LTP increases the number of AMPA receptors composed of GluA1
these GluA1 subunits of the AMPA receptors have ___ important ____ sites known as ____, ____, ____
3 important phosphorylation sites known as Ser 818, Ser 831, Ser 845
P1 Ser 818 ____ GluA1 to the ____
P2 Ser 831 ____ GluA1 ____ ____
P3 Ser 845 ____ GluA1 to the ____ _____
P1 Ser 818 anchors GluA1 to the PSD
P2 Ser 831 changes GluA1 channel conductance
P3 Ser 845 traffics GluA1 to the extrasynaptic region
LTP changes the ____ of AMPA receptors that are ____ or ____ in the _____
number of AMPA receptors that are trapped or immobilized in the PSD
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 ____
- more capturing of these types of AMPA receptors to the PSD
- changes to the rate at which receptors are removed from the membrane
the LTP ____ stimulus increases ____ of ____ _____
the LTP inducing stimulus increases trapping of AMPA receptors
how does the LTP inducing stimulus increases trapping of AMPA receptors?
3 molecules important for this:
1. ____
2. ____ known as ____
3. ___-__ ____ _____
- CaMKII
- TARP known as Stargazin
- PSD-95 scaffolding proteins
how do these 3 molecules interact to increase AMPA receptor number in the synapse?
- PSD-95 scaffolding proteins form ____ ____ for _____ AMPA receptors ____ through the _____
- PSD-95 scaffolding proteins form potential slots for trapping AMPA receptors diffusing through the PSD
how do these 3 molecules interact to increase AMPA receptor number in the synapse?
- CaMKII _____ stargazin from the _____ and facilitates ____ to _____
- CaMKII phosphorylates stargazin from the membrane and facilitates binding to PSD-95
how do these 3 molecules interact to increase AMPA receptor number in the synapse?
- the binding of ____ to ____ ____ additional AMPA receptors
- the binding of stargazin to PSD-95 traps additional AMPA receptors
___ ____ are also important to AMPA receptor delivery to the ____
recycling endosomes are also important to AMPA receptor delivery to the PSD
the initial generation of LTP causes rapid trapping of the ____ ____ ____ ____ diffusing around the _____ ____ of the plasma membrane
already present AMPA receptors diffusing around the extrasynaptic regions of the plasma membrane
____ processes continue to ____ AMPA receptors from the _____
endocytotic processes continue to remove AMPA receptors from the PSD
recycling endosomes contain ____ ____ ____ of AMPA receptors
___ ___ through the ____ receptors results in ____ of the _____ to the ____ ____ where these receptors can more slowly enter the ____
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
in terms of the increase in AMPA receptors in the PSD, calcium engages 2 independent processes:
- ___ ____ of ____ AMPA receptors that are ____ around the ____ ____
- ___ ____ of ___ ___ of AMPA receptors from the ____ to the ___ ____
- rapid trapping of existing AMPA receptors that are diffusing around the plasma membrane
- slower exocytosis of additional pools of AMPA receptors from the endosomes to the plasma membrane
rapid ____ of AMPA receptors based on _____ of basal AMPA receptor ____ processes are important for LTP
insertion of AMPA receptors based on reorganization of basal AMPA receptor trafficking processes are important for LTP
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 ____ _____
actin filaments within the spine must be rapidly degraded
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 ____
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
how are LTP processes stabilized?
(___ ___) -> ____ ____ -> (____) -> ___-___ ____ -> (____) -> ___-___ ____
(sensory input) -> sensory memory -> (attention) -> short-term memory -> (encoding) -> long-term memory
regarding sensory memory, ____ info is ___
unattended info is lost
regarding short-term memory, ____ info is ____
unrehearsed info is lost
regarding long-term memory, some info may be lost ____
overtime
LTP also evolves in ____
stages
delivery of ____-____ stimulus prevents ____ of ____ _____ when occurring within ____ ____ of TBS-inducing stimulus
low-frequency stimulus prevents development of lasting LTP when occurring within a minute of TBS-inducing stimulus
___-___ stimulation does not prevent ____ of a _____ ____ when delivered at least ___ ___ after TBS stimulation
low-frequency stimulation does not prevent emergence of a durable LTP when delivered at least 10 minutes after TBS stimulation
these finding indicate that the ____ ___ that support LTP are ___ ____ ____
but within about ___ ____, ____ ____ work to ____ these ____ ____ and ____ ____ to _____
synaptic changes that support LTP are not initially stable
10 minutes, additional process work to stabilize these synaptic changes and decrease vulnerability to disruption
for LTP to endure longer that 30 minutes, ___ ___ must be ____ to create a ____ ____ ____ that will:
prevent ____ processes that ____ ____ ____ from the ____
ensure ____ of a ___ ___ of ____ ____
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
during the 30 minute period after LTP induction, ____ ____ are recruited that change the ____ of the ____
additional processes are recruited that change the architecture of the spine
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 ____ ____
stabilization phase and it involves remodeling of the dendritic spine
dendritic spines have diverse ___ and ____
shapes and sizes
dendritic spines are ____ and constantly ___ and ____ on _____
dynamic and constantly extending and retracting on dendrites
the size of dendritic spines determines ___ ___ they will _____
larger spines ___ much ____ than small spines
how long they will endure
larger spines endure much longer than small spines
dendritic spine size is highly correlated with the ____ of ___ ____ in the _____
number of AMPA receptors in the PSD
these large dendritic spines can endure for ____ in living animals
days in living animals
processes that create ___ ____ are critical to ____ of ____ synapses and thus key to ____ and ____
large spines are critical to stability of potentiated synapses and thus key to LTP and memory
changes in dendritic spine ____, ____, and _____ underlie ___ changes due to _____
density, size, and plasticity underlie cognitive changes due to age
___ ___ within spines is key to stabilizing LTP
actin polymerization within spines is key to stabilizing LTP
____ is the major _____ component of dendritic spines
actin is the major cytoskeleton component of dendritic spines
actin molecules exist in ____ ____: ____-actin and ___-actin
2 states: G-actin and F-actin
polymerization results in the formation of a _____, which is a large molecule formed by ____ ___ ____
polymer, which is a large molecule formed by combining smaller molecules
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 ____
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
actin exists in 2 states:
single arrow tips represent the ____ state, __-actin
strings of arrows represent ____ actin (___-actin), its ____ state
monomer state, G-actin
filament actin (F-actin), its polymer state
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
turnover similar to a treadmill
old units are removed from the pointed end, and new units are added to the barbed end
the ____ of ____ regulates actin _____
the state of cofilin regulates actin polymerization
the state of cofilin regulates actin polymerization:
- in its normal, ____ state, cofilin ____ and _____ actin filaments
- when ____ by _____, ____ (____) no longer interferes with ____ ____
- in its normal, unphosphorylayted state, cofilin severs and depolymerizes actin filaments
- when phosphorylated by LIMK, cofilin (pcofilin) no longer interferes with actin polymerization
actin polymerization is necessary to ____ ____
stabilize LTP
when drugs (such as latrunculin and cytochalasin) that ____ ____ ____ are applied before TBS, they ___ ____ ____ the ____ of LTP, but it ___ ____ (___ is affected, not ____)
prevent actin polymerization are applied before TBS, they do not prevent the generation of LTP, but it rapidly decays (stability is affected, not generation)
LTP is ____ if these drugs that prevent actin polymerization are applied ____ minutes after LTP is _____
thus, ____ ___ is necessary to ____ LTP, but not to ____ LTP
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
