Short and Long Term Plasticity Flashcards by Genevieve Benjamin

Plasticity: changes in _____ function as a result of _____

Neuronal

Experience

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What does “experience” refer to in terms of plasticity?

Prior excitation or inhibition

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Plasticity enables the _____ to change the _____.

Environment

Neuron

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Plasticity always requires _____ signaling.

Intracellular

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Plasticity can last from _____ to ____ and ____ (time frame).

mSec

Hours and days

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Plasticity can change neurons in what 4 ways?

Excitability of neuron (ability to fire action potential)
Ability of neuron to signal to another neuron
Number and type of synapses on a neuron
How many other neurons it synapses with

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Plasticity underlies ____ and ____ at both the cellular and organismal level.

Learning

Memory

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Of the methods of synaptic strength modulation, which 4 are considered short term? Which one has the shortest time frame?

Facilitation
Depression
Augmentation
Potentiation
Shortest time frame: facilitation

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Synaptic strength is related to what?.

Amplitude of depolarization

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Facilitation: increase or decrease synaptic strength, time scale

Increase

mSec

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Depression: increase or decrease synaptic strength, time scale

Decrease

mSec-seconds

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Augmentation: increase or decrease synaptic strength, time scale

Increase

Seconds

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Potentiation: increase or decrease synaptic strength, time scale

Increase

Minutes

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Habituation: increase or decrease synaptic strength, time scale

Decrease

Minutes

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Sensitization: increase or decrease synaptic strength, time scale

Increase

Minutes-hours

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Long-term depression: increase or decrease synaptic strength, time scale

Decrease

Hours-days

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Long-term potentiation: increase or decrease synaptic strength, time scale

Increase

Hours-days

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As a general rule, the longer the time scale of modulation, the more ____ and greater _____ of mechanisms underlie it.

Complex

Number

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Many of the long-term mechanisms of synaptic modulation proceed through ___-____ pathways first.

Short-term

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In facilitation, what difference would you see in membrane potential (Vm) between the pre- and post-synaptic neuron? What is happening on the pre-synaptic side that causes this phenomenon?

Post-synaptic neuron has an increase in Vm

Greater vesicle release on the pre-synaptic side

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Facilitation is due to the fact that after an action potential, clearing of ____ (ion) from the pre-synaptic side is relatively ____ (speed).

Ca+2

Slow

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In facilitation, if the interval between action potentials is short and the Ca+2 from the previous action potential has not been cleared, what is the effect on Ca+2 concentration and synaptic vesicle release?

Ca+2 concentration increases

More synaptic vesicles are released

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Facilitation has a direct relationship with what action potential-related phenomenon? What about this relationship yields the short time frame under which facilitation occurs?

Minimum interspike interval (minimum interval between action potentials)
Minimum interspike interval is short, so facilitation is short

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Depression causes an (increase/decrease) in post-synaptic membrane potential at high stimulation. Why?

Decrease

Pool of vesicles is depleted, so ability of pre-synaptic cell to cause depolarization is decreased

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Of depression and augmentation, which is seen at normal pre-synaptic Ca+2 levels? Which is seen at low pre-synaptic Ca+2 levels?

Depression | Augmentation

Augmentation causes an (increase/decrease) in post-synaptic membrane potential at high stimulation. What causes this, and what about pre-synaptic Ca+2 levels makes this effect visible?

Increase High stimulation causes more vesicles to be released Low pre-synaptic Ca+2 levels slows down molecular machinery, so effect of increased vesicle fusing is seen

Potentiation is observed under (lower/higher) pre-synaptic stimulation than in the depression experiments.

Lower

In potentiation, increase in intracellular ____ (ion) activates _____ that ______ proteins involved in ____ release. What effect does this have on the proteins, and thus post-synaptic membrane potential?

``` Ca+2 Kinases Phosphorylate Vesicle Increases activity of proteins Increases membrane potential ```

The model organism Aplysia is what type of animal?

Sea slug

Aplysia has 2 sensory neurons, one at the _____ skin and one at the ____. What neurotransmitter do these sensory neurons release?

Siphon Tail Glutamate

The siphon skin sensory neuron of Aplysia synapses onto a ____ neuron that is attached to the ____. What neurotransmitter does the latter neuron release?

Motor Gill Acetylcholine

Poking the siphon of Aplysia causes its ____ neuron to release _____, which activates ____ release by the ____ neuron that triggers gill _____.

``` Sensory Glutamate Acetylcholine Motor Retraction ```

The tail sensory neuron of Aplysia synapses onto a ___ ___, which releases ____ (neurotransmitter) onto the ___ neuron of the ____, which changes its ability to release ____.

``` Modulatory interneuron Serotonin Sensory Siphon Glutamate ```

In Aplysia, touching the siphon causes an action potential in the ____ neuron, which triggers an excitatory post-synaptic potential in the ____ neuron, which causes ____ contraction.

Sensory Motor Gill

Habituation in Aplysia: repeated touching of the siphon causes a ____ in motor neuron excitatory post-synaptic potential, leading to ____ contraction of the gill.

Decrease | Lessened

Sensitization in Aplysia: what is done to the tail before touching the siphon? What effect does this have on motor neuron post-synaptic potential and gill contraction?

Tail is shocked | Increases motor neuron post-synaptic potential and magnitude of gill contraction

In habituation, repeated stimulation of the same pathway leads to ____ response.

Lessened

Of habituation and sensitization, which is considered to be multi-trial circuit learning and which is considered to be single trial learning? Why?

Habituation- multi-trial circuit learning (effect only seen after multiple stimulations) Sensitization- single trial learning (effect seen after only 1 stimulation)

In Aplysia habituation, which is lessened with repeated stimulation, the action potential of the sensory neuron or the action potential of the motor neuron? What is happening at the neurotransmitter level that causes that change?

Action potential of motor neuron | Sensory neuron is releasing less glutamate onto motor neuron, so excitation isn't as strong

In Aplysia sensitization, shocking the tail causes the sensory neuron to release what? Modulatory interneuron to release what? How does this effect the siphon sensory neuron's ability to release its neurotransmitter upon stimulation through poking? What effect does this then have on the motor neuron?

Shocking tail -> glutamate release by tail sensory neuron -> serotonin release by modulatory interneuron -> increased glutamate release by siphon sensory neuron Increased glutamate release means increased excitation of motor neuron, so stronger gill withdrawal

In Aplysia sensitization, release of serotonin on the siphon sensory neuron activates what type of serotonin GPCR (Gs, Gi, or Gq) on the (siphon sensory neuron/modulatory interneuron)?

Gs | Siphon sensory neuron

Aplysia sensitization: Activation of serotonin Gs coupled GPCR in the siphon sensory neuron stimulates _____ to make ____, which activates ____ ____ ___.

Adenylyl cyclase cAMP Protein kinase A

Aplysia sensitization: Activation of serotonin Gs coupled GPCR in the siphon sensory neuron causes protein kinase A to phosphorylate what 2 types of voltage-gated channels? What effect does phosphorylation have on each of the 2 channels? How does this affect the action potential and neurotransmitter release?

VG K+ channels: decreases activity VG Ca+2 channels: increases activity Increases length of action potential and neurotransmitter release

Aplysia sensitization: Persistent changes in protein kinase A activity caused by activation of serotonin GPCR of siphon sensory neuron leads to (long-term/short-term) changes in gene expression of sensory neuron through activation of what transcription factor?

Long-term | CREB

In the case of patient HM, what happened to his memories from more than 3 years before the removal of his hippocampus? Less than 3 years before? How was his ability to form new memories affected after the surgery? What was the conclusion from his case?

More than 3 years before: intact Less than 3 years before: partially lost Lost ability to form new memories Hippocampus is required for formation of new memories

What is the difference between retrograde and anterograde amnesia?

Retrograde: lose old memories Anterograde: lose ability to form new memories

What is the difference between declarative and procedural memory?

Declarative is explicit (can be recalled) | Procedural is implicit (skill-based)

In declarative memory, what part of the brain is important for creating memories, and which part of the brain is responsible for storing them?

Creating memories: hippocampus | Storing memories: pre-frontal cortex

What are 3 parts of the brain involved in procedural memory? Is procedural memory controlled by the hippocampus?

Striatum, cortex limbic system, cerebellum | Hippocampus isn't involved

1) Neurons carrying information that enters the mouse hippocampus synapse on the ____ cells in the ____ ____. 2) The ____ cells synapse on the ____ cells. 3) The ____ cells synapse on the ____ cells. The neurons that connect these 2 types of cells are also called ____ ____.

``` 1) Granule cells Dentate gyrus 2) Granule cells CA3 3) CA3 CA1 Schaffer collaterals ```

Which of the 3 regions of the mouse hippocampus is usually used to study synaptic plasticity? Why?

CA3 to CA1 (Schaffer collaterals) | Most organized and most homogenous

What type of memory is assessed through the Morris water maze? How is it assessed? How would a mouse with a hippocampal lesion perform on this test?

Spatial reference memory Mouse has to swim through opaque water to find platform using spatial orientation guides Mouse with hippocampal lesion wouldn't show improvement on test by finding platform more quickly after multiple trials

What type of memory is assessed through the Pavlovian fear conditioning test? How is it assessed? How would a mouse with a hippocampal lesion perform on this test?

Associative memory Mouse is put in box and then shocked- on subsequent trials, mouse shows fear upon being placed in box Mouse with hippocampal lesion wouldn't show fear upon being placed in box after previously being shocked

What type of memory is assessed through the novel object recognition test? How is it assessed? How would a mouse with a hippocampal lesion perform on this test?

Recognition memory Mouse is presented with a familiar object (has seen before in a previous trial) and an unfamiliar object- amount of time mouse spends investigating each object is measured Mouse with hippocampal lesion would show equal time investigating familiar and unfamiliar objects

Long-term potentiation: (Brief/long) period of (low/high) frequency stimulation of Schaffer collaterals causes an increase of ____ (ion) and subsequent ____ release from the Schaffer collaterals. What is the effect seen in the CA1 cells? Is there an increase or decrease in synaptic strength seen? Does this effect last following the return to baseline stimulation of Schaffer collaterals?

``` Brief High Ca+2 Vesicle Increased excitatory post-synaptic potential (EPSP) Increase in synaptic strength Yes ```

Mutations or treatments that interfere with long-term potentiation or depression affect performance in what tests?

Behavioral tests of memory

Specificity of long-term potentiation: 2 Schaffer collateral pathways synapsing on same CA1 neuron- what was the difference in how the 2 were stimulated prior to receiving a single stimulus? What was the result for each pathway following the single stimulus? What was the conclusion?

1 pathway received high frequency stimluation, the other received no stimluation The stimulated pathway showed long-term potentiation, the other did not Conclusion: long-term potentiation is specific to the active synapse

Associativity of long-term potentiation: 2 Schaffer collateral pathways synapsing on same CA1 neuron- what was the difference in how the 2 were stimulated prior to receiving a single stimulus? What was the result for each pathway following the single stimulus? What was the conclusion?

1 pathway received high frequency stimulation, the other received low frequency stimulation Both pathways showed long-term potentiation Conclusion: synapses whose activity (firing pattern) is associated in time will undergo long-term potentiation, even if they didn't all receive the high-frequency stimulus

High-frequency stimulation as in the long-term potentiation experiments can also be called what?

Tetanic stimulation/ tetanus

What is the phrase coined by Hebb? Hebbian plasticity requires (specificity/associativity/both). Why?

"Neurons that fire together wire together" Both Only neurons that are active together will undergo synaptic strengthening (specificity) and neurons that are active at the same time will undergo synaptic strengthening (associativity)

Hebbian plasticity: when groups of synchronous neurons fire onto a target neuron, what happens to the synaptic strength of that pathway? How is this different from when groups of asynchronous neurons fire onto a target neuron? Why is this phenomenon observed?

Synchronous: pathway is strengthened and new synapses are added Asynchronous: pathway is lost (synapses are removed) In order to maintain homeostasis of nervous system, favoring of synchronous pathway requires loss of asynchronous pathway

In long-term potentiation, 2 things happen with the AMPA receptors that enable increased synaptic strength: 1) The kinases ___ ___ ___ and ___ ____ ___ ___ activate AMPA receptors through _____. 2) ____ signaling pathway triggers _____ to induce the ___ ____ to put more AMPA receptors on the _____ ____. Both changes are due to activation of ___-dependent _____. Ca+2 in this pathway enters through what receptors?

``` 1) Protein kinase C, Ca calmodulin kinase II (CaMKII) Phosphorylation 2) Kinase Synaptotagmin Recycling endosome Plasma membrane Ca+2-dependent kinases NMDA ```

NMDA receptors are said to be "dual sensors" because they require both (depolarization/hyperpolarization) from the ____ receptors to remove the ____ block as well as _____ (neurotransmitter) binding in order to pass current.

Depolarization AMPA Mg+2 Glutamate

What 2 types of synapses would only contain NMDA receptors without AMPA receptors? What are these synapses termed, and why?

Immature synapses or synapses following long-term depression "Silent synapses": little to no current passes through them because they don't receive necessary depolarization from AMPA receptors

Is long-term potentiation restricted to one region of the brain? Does it require high or low frequency stimulation to occur?

No | High

Long-term depression: (Brief/long) period of (low/high) frequency stimulation of Schaffer collaterals causes an increase of ____ (ion) and subsequent ____ release from the Schaffer collaterals, which (increases/decreases) over period of stimulation until ____ is reached. What is the effect seen in the CA1 cells after returning to baseline measurements? Is there an increase or decrease in synaptic strength seen? Does this effect last following the return to baseline stimulation of Schaffer collaterals?

``` Long Low Ca+2 Vesicle Decreases Baseline Decreased excitatory post-synaptic potential (EPSP) Decrease in synaptic strength Yes ```

In long-term depression, low level Ca+2 stimulation for a long period of time causes 2 things to happen with the AMPA receptors that enable decreased synaptic strength: 1) The phosphatase ______ decreases activation of AMPA receptors through _____. 2) ____ of AMPA receptors is induced, which causes (placement/removal) of AMPA receptors from the plasma membrane. Both changes are due to activation of ___-dependent _____. Ca+2 in this pathways enters through what receptors?

``` 1) Calcineurin Dephosphorylation 2) Endocytosis Removal Ca+2-dependent phosphatases NMDA ```

How are long-term potentiation and long-term depression affected by knocking out CaMKII?

LTP: none observed LTD: shorter lasting

How are long-term potentiation and memory affected by overexpressing CaMKII?

LTP: increased Memory: decreased

How are long-term potentiation, long-term depression, and memory affected by overexpressing the NMDA GluN2A subunit? What does this indicate?

LTP: no effect LTD: decreased Memory: decreased LTD is important for memory

What about the cause of short-term depression makes it short-term?

Short-term depression is caused by depletion of synaptic vesicles, and it doesn't take very long to make more vesicles

In Hebbian plasticity, only neurons that are activated when (relative to each other) have their synapses strengthened?

At the same time

Much of what is known about LTP and LTD has been learned from studying what type of synapses (neurotransmitter specific)? Is it possible for other types of synapses to be changed by experience?

Glutamatergic | Yes

What are the protrusions of dendrites called? The skinny part of these structures is called the ____, and the large bulbous part is called the _____.

Dendritic spines Neck Head

On what part of the dendritic spine is the post-synaptic density and synapse site located?

Spine head

What is the effect of LTP on dendritic spine size? LTD?

LTP: bigger spines LTD: smaller spines

Dendritic spine heads specifically contain what 2 types of glutamatergic receptors?

AMPA | NMDA

Dendritic spines can be seen in the ____ neurons of the ____ and _____, the ___ ___ neurons of the ____, and the ____ neurons of the ____.

``` Pyramidal Cortex Hippocampus Medium spiny Striatum Purkinje Cerebellum ```

Abnormalities of dendritic spines are associated with what type of condition?

Intellectual disability

How does measuring the effects of cocaine exposure on dendritic spine size show that changes in spines are dynamic?

Cocaine exposure could either cause spine head size to increase or decrease depending on how long afterwards you measure it

In a healthy adult animal, are there generally major changes in dendritic spines as a result of normal plasticity? What kinds of changes are seen?

No | Shapes and numbers of spines

When LTP is induced, what happens to the size of the stimulated dendritic spine head and the magnitude of AMPA receptor current? What phenomenon underlies these observations?

Dendritic spine head size increases AMPA receptor current increases Both caused by increased number of AMPA receptors

The effects of LTP are seen (only in the stimulated dendritic spine/ in stimulated and neighboring dendritic spines).

Only in the stimulated dendritic spine

When LTD is induced, what happens to the size of the stimulated dendritic spine and the magnitude of AMPA receptor current? What phenomenon underlies these observations?

Dendritic spine head size decreases AMPA receptor current decreases Both caused by decreased number of AMPA receptors

When the dendritic spine is stimulated, there is an increase in what ion that is primarily restricted to what part of the spine?

Ca+2 | Head

____ (ion) enters the dendritic spine ____ through the ____ receptors.

Ca+2 Head NMDA

What part of the dendritic spine is said to restrict Ca+2 to the head?

Neck

Dendritic spines, which are considered to be (pre-/post-) synaptic, are called Ca+2 micro-domains for what reason?

Post-synaptic | Ca+2 enters through them and triggers signalling within them

Ca+2 in dendritic spines activates what kinase that phosphorylates what 2 receptors that are important in LTP?

CaMKII | AMPA, NMDA

Is it with a short or a long neck that Ca+2 increase is limited to the dendritic head? Is it with a short or long neck that Ca+2 can diffuse from the dendritic head to the dendritic shaft? In which case is the area of strengthening restricted to just one synapse?

Long Short Long

Stimulation of a single dendritic spine: in _____ (timeframe), there is a short transient increase in ____ (ion) in the stimulated spine. This transient increase causes activation of _____ (kinase) already in the stimulated spine, which takes place in a time frame of ____. Activation of this kinase causes ____ (plasticity type) in the stimulated spine which triggers more ____ (kinase) to enter the spine, all occurring under a time frame of ____.

``` Milliseconds Ca+2 CaMKII Seconds LTP CaMKII Minutes ```

LTP in the dendritic spine: (low/high) frequency stimulation causes _____ to flow in through the ____ receptor. This ion activates ______ (kinase) which can do one of 2 things: 1) Stimulate ___ or ____ receptors 2) Activate ____- _____ kinase signaling pathway that triggers ____ of AMPA receptors to the ___ zone

``` High Ca+2 NMDA CaMKII AMPA or NMDA Ras-MAP kinase Exocytosis Active ```

What type of plasticity causes growth of or increase in dendritic spines? What about the time frame of this type of plasticity enables these changes?

LTP | It is long-lasting (short-lasting forms of plasticity won't cause this change)

What is the effect of blocking protein synthesis on long-lasting LTP (time frame of hours)? What are 2 things that long-lasting LTP requires?

Decrease LTP | LTP requires protein synthesis and changes in gene expression (CREB)

More synapses can be made by making additional ___ ___.

Dendritic spines

LTP that is pre-synaptic can occur through an increase in ____ synthesis.

Neurotransmitter

Pre-synaptic LTP mechanism: high frequency stimulation changes ___ (ion) levels, which activates _____ that phosphorylate ____ ____ (enzyme), causing it to make more dopamine.

Ca+2 Kinases Tyrosine hydroxylase

Long-term changes associated with post-synaptic LTP can occur through activation of CREB, which controls what?

Transcriptional regulation

Post-synaptic LTP mechanism: CREB can be activated through what 3 kinases?

Protein kinase A CaMKII MAP kinase

Pre-synaptic LTP can also occur by changing the machinery responsible for what? How does this increase synaptic strength?

Docking and priming of vesicles | Increases neurotransmitter release

Post-synaptic LTD can also occur by activating which receptors, which decrease the availability of which receptors (also decreased in the NMDA-dependent LTD pathway)?

Metabotropic glutamate receptors | AMPA receptors

Endocannabinoids in LTD are synthesized by the (pre-/post-)synaptic neuron and act on the (pre-/post-)synaptic neuron in what way? How does this decrease synaptic strength?

Post-synaptic Pre-synaptic Trigger decreased vesicle release Decreases neurotransmitter release

Habituation at the molecular level involves decreased activity of (pre-/post-)synaptic ____-____ ____ channels, which cause decreased synaptic strength how?

Pre-synaptic Voltage-gated Ca+2 channels Decrease number of vesicles (and thus neurotransmitter) released

What is the main difference between Hebbian and homeostatic plasticity?

Hebbian plasticity looks at changes in one or a small group of synapses, whereas homeostatic plasticity looks at changes in all the synapses in a given neuron

Homeostatic plasticity involves balancing the effects of ____ synapses with the ____ activity.

Individual | Overall

Do the same LTD and LTP mechanisms apply in homeostatic plasticity as in Hebbian plasticity? What is the difference?

Yes | Larger scale in homeostatic plasticity