Lecture 5 - Induction and Expression of LTP

Question 1

postsynaptic potentials can be recorded from either an _____ ____ that penetrates the neuron or an _____ placed in the _____ _____

Answer 1

intracellular electrode that penetrates the neuron or an electrode placed in the extracellular fluid

Question 2

the intracellular electrode detects ___ ____ flowing ___ the neuron, indicating ____

Answer 2

positive ions flowing into the neuron, indicating depolarization

Question 3

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

Answer 3

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

Question 4

the slope represents the _____ of ____ in ____ you’re getting

Answer 4

strength of change in plasticity you’re getting

Question 5

LTP represents an ___ in ___ ___

Answer 5

increase in synaptic strength

Question 6

synaptic strength is measured as the amount of ____ ____ (____) produced by the ____

Answer 6

amount of postsynaptic depolarization (EPSP) produced by the stimulus

Question 7

the slope of the extracellular recording reflects ____ ____ ___ ___ flow ____ the ____ ____ and the ____ of _____

Answer 7

how many positive ions flow into the postsynaptic neuron and the strength of LTP

Question 8

LTP is viewed as a ____ ____ of ____ ____

it provided researchers with a means to study the ____ and ____ ____ that underly ____ ____

Answer 8

cellular hallmark of synaptic plasticity

cellular and molecular changes the underly synaptic plasticity

Question 9

the synapse is a ____, ____ region

the entire complement of molecules can turn over ___ or ____ times a ___

Answer 9

happening, dynamic region

2 or 3 times a day

Question 10

the _____ ____ (___) occupies the synaptic cleft

Answer 10

extracellular matrix (ECM) occupies the synaptic cleft

Question 11

the extracellular matrix (ECM) is composed of molecules that are synthesized and secreted by ___ and ___ ____

Answer 11

synthesized and secreted by neurons and glial cells

Question 12

the extracellular matrix (ECM) forms a ____ between the ____ and ___-____ ____, and the molecule it contains interact with ____ in order to influence their ____

Answer 12

bridge between the pre and post-synaptic neuron and the molecules it contains interact with both to influence their function

Question 13

a feature of the excitatory synapses is a ___ of the ____ ____

this area is referred to as the ____-____ ____ (___)

Answer 13

thickening of the postsynaptic membrane

post-synaptic density (PSD)

Question 14

the PSD contains ____ ___ ____ that include ____ ____, ____ ____, ____ ____, and ___ ___ (e.g. ____-___)

Answer 14

several hundred proteins that include glutamate receptors, ion channels, signaling enzymes, and scaffolding proteins (e.g. PSD-95)

Question 15

PSD is a ___ ___ that helps to ___ the ___ and ___-____ ____

it also helps to position ____ ___ near ____ ___ so that these ___ ___ can be ___ and ___ to ___-___ change

Answer 15

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

Question 16

____ is another important protein in the synapse that provides ____

Answer 16

actin is another important protein in the synapse that provides scaffolding

Question 17

actin helps to provide the ‘____’ by which important ____ can be moved to the ____

Answer 17

‘highways’ by which important proteins can be moved to the PSD

Question 18

functional proteins are ____ that can ____ ____ and ____ the ____ of other proteins

Answer 18

enzymes that can catalyze reactions and modify the function of other proteins

Question 19

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 ____ ____

Answer 19

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

Question 20

why focus on excitatory synapses?

changes in ___ ____ produced by events that lead to LTP are primarily the result of ____ of ____ ____

Answer 20

synaptic potentials produced by events that lead to LTP are primarily the result of modifications of excitatory synapses

Question 21

the post-synaptic component of excitatory synapses is a ____ ____

these ___ ____ contain ______-____ _____ called ____ ____

Answer 21

dendritic spine

dendritic spines contain membrane-spanning receptors called glutamate receptors

Question 22

LTP is a long-lasting _____ in _____ ____ that occurs after _____ _____ of a _____

Answer 22

LTP is a long-lasting increase in synaptic strength that occurs after repeated stimulation of a synapse

Question 23

glutamate receptors are anchored into the ____ by proteins called _____

so that they don’t ____ ___ from the ____ (within the ____)

other anchoring proteins are ____, ____, _____, and ____

Answer 23

membrane by proteins called PSD-95

move away from the synapse (within the membrane)

SynGAP, GKAP, Shank, Homer

Question 24

____ ____ are key to synaptic modifications

Answer 24

signaling cascades are key to synaptic modifications

Question 25

plasticity refers to the brain’s ability to ____ and ____ in response to ____ ____ or ____

Answer 25

the brain’s ability to adapt and change in response to new information or injury.

Question 26

the plasticity that occurs during LTP (and memory) begins with the _____ of ____ from the _____ _____

this activates important ____ ____ that are key to producing ___-____ ____ in the ____

Answer 26

release of glutamate from the presynaptic neuron

signaling pathways that are key to producing long-lasting changes in the synapse

Question 27

simple schematic of signaling cascade:

1. ___ ___ (ex: ____)
2. ___ ___ (ex: ____, ___)
3. ____
4. _____ / ____
5. ____ and ____ ____

Answer 27

1. first messenger (ex: glutamate)
2. second messenger (ex: cAMP, IP3)
3. proteins
4. kinases / phosphatases
5. structural and functional proteins

Question 28

the framework approach to LTP is guided around 3 principles (____ / ____ ____ / ____)

Answer 28

duration / molecular changes / stages

Question 29

the principles of the framework to approach LTP are:

1. ___ / ____
2. _____ mechanisms
3. _____ / ____
   4 ____

Answer 29

1. generation / induction
2. stabilization mechanisms
3. consolidation / expression
4. maintenance

Question 30

LTP induction requires _____ ____

Answer 30

NMDA receptors

Question 31

increase in # of ____ receptors supports LTP ____

Answer 31

AMPA receptors supports LTP expression

Question 32

NMDA receptors have a ____ ____

a significant ____ must happen in order to ____ this ____

Answer 32

magnesium block

depolarization must happen in order to remove this block

Question 33

NMDA receptor antagonist APV prevents ____ of LTP but has no effect on its _____

AMPA receptor antagonist CNQX prevents both the ____ and ___ of LTP

Answer 33

induction of LTP but has no effect on its expression

induction and expression

Question 34

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 ____ ____

Answer 34

calcium into the post-synaptic cell

glutamate must bind to the receptor, and the cell must depolarize in order to remove the magnesium plug

Question 35

pharmacological agents that antagonize AMPA receptors prevent LTP _____ (not surprisingly since AMPA receptors are key to ____ ____)

Answer 35

expression (not surprisingly since AMPA receptors are key to Na+ influx)

Question 36

expression of LTP involves an ____ in ____ receptors in the region of the _____

Answer 36

increase in AMPA receptors in the region of the PSD

Question 37

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 ____ _____

Answer 37

glutamate, their channels open longer

increased number of AMPA receptors in the dendritic spine

Question 38

once LTP is induced, the expression of LTP only requires ____ of ____ ____

these post-translational processes are ____ ____ ____ that cause 2 main processes to occur

Answer 38

rearrangement of existing receptors

mediated signaling cascades that cause 2 main processes to occur

Question 39

these two processes are:

AMPA receptors are ____ ____ to the ____

the ___ ____ in the ____ ____ is temporally ____

Answer 39

rapidly delivered to the PSD

actin cytoskeleton in the spine head is temporally degraded

Question 40

it now appears safe to state that the major mechanism for the expression of LTP involves ____ the ____ of ____ ___ in the ___ ___ at ____ via ___-___ changes in ____ ____ ____

Answer 40

increasing the number of AMPA receptors in the plasma membrane at synapses via activity-dependent changes in AMPA receptor trafficking

Question 41

a central theory of LTP is that the AMPA receptor numbers ____ in the ____ ____

Answer 41

increase in the dendritic spines

Question 42

AMPA receptors traffic ___ and ____ of the ___

Answer 42

into and out of the spines

Question 43

this occurs with and without ___ ___

____ trafficking

____-___ trafficking

Answer 43

synaptic activity

constitutive trafficking

activity-induced trafficking

Question 44

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 _____

Answer 44

into and out of the dendritic spines

surface and in the intracellular space of the dendritic spine

PSD and others are extrasynaptic

Question 45

AMPA receptors are captured by ____ in the ____ ___ and ____ back to the ____

Answer 45

proteins in the endocytotic zone and recycled back to the membrane

Question 46

_____ processes deliver AMPA receptors to the ____ in 3 steps

Answer 46

constitutive processes deliver AMPA receptors to the membrane in 3 steps

Question 47

these 3 steps are:

1. intracellular _____ containing ____ ____ (called ____) are ____ to deliver these ____ ____ to the region near the ____
2. these receptors then ____ ___ along the ____ to enter the ____
3. some receptors are ____ there and other leave the ____ and are ___ back to the _____

Answer 47

1. intracellular vesicles containing AMPA receptors (called endosomes) are mobilized to deliver these AMPA receptors to the region near the PSD
2. these receptors then diffuse randomly along the membrane to enter the PSD
3. some receptors are trapped there and other leave the PSD and are recycled back to the endosomes

Question 48

AMPA receptors can be composed of _____ ____

Answer 48

different subunits

Question 49

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 ____ ____

Answer 49

GluA2 subunits

GluA1 subunits

phosphorylation sites

Question 50

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 ___ (__)

Answer 50

GluA1

Ser818 (P1), Ser 831 (P2), Ser 845 (P3)

Question 51

P1 Ser 818 _____ GluA1 to the ____

P2 Ser 831 ____ GluA1 ____ ____

P3 Ser 845 ____ GluA1 to the ____ ___

Answer 51

P1 Ser 818 anchors GluA1 to the PSD

P2 Ser 831 changes GluA1 channel conductance

P3 Ser 845 traffics GluA1 to the extrasynaptic region

Question 52

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 ____

Answer 52

• more capturing of these types of AMPA to the PSD
• changes to the rate at which receptors are removed from the membrane