Lecture 5 - Induction and Expression of LTP Flashcards
postsynaptic potentials can be recorded from either an _____ ____ that penetrates the neuron or an _____ placed in the _____ _____
intracellular electrode that penetrates the neuron or an electrode placed in the extracellular fluid
the intracellular electrode detects ___ ____ flowing ___ the neuron, indicating ____
positive ions flowing into the neuron, indicating depolarization
the extracellular electrode measures the ___ ___ btw the ____ ___ and a ___ ____
when synapses depolarize, ___ ___ move away from the ___ of the ____ into the ___
this results in the electrical ____ btw the ____ ___ and ___ ___ becoming ____
thus, the extracellular recording has a ____ slope
electrical potential between the extracellular fluid and a ground electrode
positive ions move away from the tip of the electrode into the neuron
electrical potential between the extracellular fluid and ground electrode becoming negative slope
the slope represents the _____ of ____ in ____ you’re getting
strength of change in plasticity you’re getting
LTP represents an ___ in ___ ___
increase in synaptic strength
synaptic strength is measured as the amount of ____ ____ (____) produced by the ____
amount of postsynaptic depolarization (EPSP) produced by the stimulus
the slope of the extracellular recording reflects ____ ____ ___ ___ flow ____ the ____ ____ and the ____ of _____
how many positive ions flow into the postsynaptic neuron and the strength of LTP
LTP is viewed as a ____ ____ of ____ ____
it provided researchers with a means to study the ____ and ____ ____ that underly ____ ____
cellular hallmark of synaptic plasticity
cellular and molecular changes the underly synaptic plasticity
the synapse is a ____, ____ region
the entire complement of molecules can turn over ___ or ____ times a ___
happening, dynamic region
2 or 3 times a day
the _____ ____ (___) occupies the synaptic cleft
extracellular matrix (ECM) occupies the synaptic cleft
the extracellular matrix (ECM) is composed of molecules that are synthesized and secreted by ___ and ___ ____
synthesized and secreted by neurons and glial cells
the extracellular matrix (ECM) forms a ____ between the ____ and ___-____ ____, and the molecule it contains interact with ____ in order to influence their ____
bridge between the pre and post-synaptic neuron and the molecules it contains interact with both to influence their function
a feature of the excitatory synapses is a ___ of the ____ ____
this area is referred to as the ____-____ ____ (___)
thickening of the postsynaptic membrane
post-synaptic density (PSD)
the PSD contains ____ ___ ____ that include ____ ____, ____ ____, ____ ____, and ___ ___ (e.g. ____-___)
several hundred proteins that include glutamate receptors, ion channels, signaling enzymes, and scaffolding proteins (e.g. PSD-95)
PSD is a ___ ___ that helps to ___ the ___ and ___-____ ____
it also helps to position ____ ___ near ____ ___ so that these ___ ___ can be ___ and ___ to ___-___ change
scaffolding protein that helps to bind the pre and post-synaptic neuron
signaling molecules near glutamate receptors so that these signaling molecules can be activated and lead to long-term change
____ is another important protein in the synapse that provides ____
actin is another important protein in the synapse that provides scaffolding
actin helps to provide the ‘____’ by which important ____ can be moved to the ____
‘highways’ by which important proteins can be moved to the PSD
functional proteins are ____ that can ____ ____ and ____ the ____ of other proteins
enzymes that can catalyze reactions and modify the function of other proteins
complexes important for the running of this mini factory:
endosomes move ____ in and out of the _____
ribosomes that are important for _____ ____ ____
smooth ER that can ____ and ____ ____, which is an imporant ____ ____
endosomes move receptors in and out of the membrane
ribosomes that are important for translating new protein
smooth ER that can sequester and release calcium, which is an important second messenger
why focus on excitatory synapses?
changes in ___ ____ produced by events that lead to LTP are primarily the result of ____ of ____ ____
synaptic potentials produced by events that lead to LTP are primarily the result of modifications of excitatory synapses
the post-synaptic component of excitatory synapses is a ____ ____
these ___ ____ contain ______-____ _____ called ____ ____
dendritic spine
dendritic spines contain membrane-spanning receptors called glutamate receptors
LTP is a long-lasting _____ in _____ ____ that occurs after _____ _____ of a _____
LTP is a long-lasting increase in synaptic strength that occurs after repeated stimulation of a synapse
glutamate receptors are anchored into the ____ by proteins called _____
so that they don’t ____ ___ from the ____ (within the ____)
other anchoring proteins are ____, ____, _____, and ____
membrane by proteins called PSD-95
move away from the synapse (within the membrane)
SynGAP, GKAP, Shank, Homer
____ ____ are key to synaptic modifications
signaling cascades are key to synaptic modifications
plasticity refers to the brain’s ability to ____ and ____ in response to ____ ____ or ____
the brain’s ability to adapt and change in response to new information or injury.
the plasticity that occurs during LTP (and memory) begins with the _____ of ____ from the _____ _____
this activates important ____ ____ that are key to producing ___-____ ____ in the ____
release of glutamate from the presynaptic neuron
signaling pathways that are key to producing long-lasting changes in the synapse
simple schematic of signaling cascade:
- ___ ___ (ex: ____)
- ___ ___ (ex: ____, ___)
- ____
- _____ / ____
- ____ and ____ ____
- first messenger (ex: glutamate)
- second messenger (ex: cAMP, IP3)
- proteins
- kinases / phosphatases
- structural and functional proteins
the framework approach to LTP is guided around 3 principles (____ / ____ ____ / ____)
duration / molecular changes / stages
the principles of the framework to approach LTP are:
- ___ / ____
- _____ mechanisms
- _____ / ____
4 ____
- generation / induction
- stabilization mechanisms
- consolidation / expression
- maintenance
LTP induction requires _____ ____
NMDA receptors
increase in # of ____ receptors supports LTP ____
AMPA receptors supports LTP expression
NMDA receptors have a ____ ____
a significant ____ must happen in order to ____ this ____
magnesium block
depolarization must happen in order to remove this block
NMDA receptor antagonist APV prevents ____ of LTP but has no effect on its _____
AMPA receptor antagonist CNQX prevents both the ____ and ___ of LTP
induction of LTP but has no effect on its expression
induction and expression
during LTP induction, the NMDA receptor allows ____ into the post-synaptic cell
in order for this to happen, ____ must bind to the receptor, and the cell must ____ in order to remove the ____ ____
calcium into the post-synaptic cell
glutamate must bind to the receptor, and the cell must depolarize in order to remove the magnesium plug
pharmacological agents that antagonize AMPA receptors prevent LTP _____ (not surprisingly since AMPA receptors are key to ____ ____)
expression (not surprisingly since AMPA receptors are key to Na+ influx)
expression of LTP involves an ____ in ____ receptors in the region of the _____
increase in AMPA receptors in the region of the PSD
potential mechanisms to explain the enhanced AMPA receptor response:
the properties of existing AMPA receptors change so that in response to _____, their ____ ____ ____
there is an ____ ____ of AMPA receptors in the ____ _____
glutamate, their channels open longer
increased number of AMPA receptors in the dendritic spine
once LTP is induced, the expression of LTP only requires ____ of ____ ____
these post-translational processes are ____ ____ ____ that cause 2 main processes to occur
rearrangement of existing receptors
mediated signaling cascades that cause 2 main processes to occur
these two processes are:
AMPA receptors are ____ ____ to the ____
the ___ ____ in the ____ ____ is temporally ____
rapidly delivered to the PSD
actin cytoskeleton in the spine head is temporally degraded
it now appears safe to state that the major mechanism for the expression of LTP involves ____ the ____ of ____ ___ in the ___ ___ at ____ via ___-___ changes in ____ ____ ____
increasing the number of AMPA receptors in the plasma membrane at synapses via activity-dependent changes in AMPA receptor trafficking
a central theory of LTP is that the AMPA receptor numbers ____ in the ____ ____
increase in the dendritic spines
AMPA receptors traffic ___ and ____ of the ___
into and out of the spines
this occurs with and without ___ ___
____ trafficking
____-___ trafficking
synaptic activity
constitutive trafficking
activity-induced trafficking
constitutive trafficking of AMPA receptors moves AMPA receptors ___ and ____ of the ____ ____
AMPA receptors are located both on the ____ and in the ___ ____ of the ____ ____
some of these receptors are within the ____ and others are _____
into and out of the dendritic spines
surface and in the intracellular space of the dendritic spine
PSD and others are extrasynaptic
AMPA receptors are captured by ____ in the ____ ___ and ____ back to the ____
proteins in the endocytotic zone and recycled back to the membrane
_____ processes deliver AMPA receptors to the ____ in 3 steps
constitutive processes deliver AMPA receptors to the membrane in 3 steps
these 3 steps are:
- intracellular _____ containing ____ ____ (called ____) are ____ to deliver these ____ ____ to the region near the ____
- these receptors then ____ ___ along the ____ to enter the ____
- some receptors are ____ there and other leave the ____ and are ___ back to the _____
- intracellular vesicles containing AMPA receptors (called endosomes) are mobilized to deliver these AMPA receptors to the region near the PSD
- these receptors then diffuse randomly along the membrane to enter the PSD
- some receptors are trapped there and other 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
however, LTP increases the number of AMPA receptors with ____ subunits
how do we know about these subunits? they have important ____ ____
GluA2 subunits
GluA1 subunits
phosphorylation sites
initial induction of LTP increases the number of AMPA receptors composed of _____
these subunits of the AMPA receptors have 3 important phosphorylation sites known as ____ (__), ____ (__), and ___ (__)
GluA1
Ser818 (P1), Ser 831 (P2), Ser 845 (P3)
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
how though does LTP change the number of AMPA receptors 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 to the PSD
- changes to the rate at which receptors are removed from the membrane
