Exam 2 Learning and Memory Chapter 5

what are the three stages of stabilization?

actin seeding, actin building, and resisting depolymerization

who formed the consolidation hypothesis?

Muller and Pilzecker

what is the consolidation hypothesis?

new memories require a long period of time to consolidate and become resistant to disruption

strong high frequency stimulation generates a _?

long lasting LTP

weak high frequency stimulation generates a _?

short lasting LTP

what is anisomycin and what does it do?

a protein synthesis inhibitor that prevents L-LTP

what is the difference between what L-LTP depends on vs S-LTP?

L-LTP depends on new proteins being generated but S-LTP does not

what does S-LTP depend on?

only on post-translational modification processes

what is the De Novo signaling hypothesis?

the idea that new proteins need to be formed for an enduring LTP

what two things does the LTP-inducing stimulus initiate (parallel effects)

local translation and genomic signaling cascades (synapse-to nucleus and soma-to-nucleus signals) that transcribe new mRNA that can then be translated

where are mRNA and post translational machinery located?

locally in the dendritic spine region

where does local protein synthesis occur?

in the dendritic spine region where ribosomes and mRNA are present

synaptic activity initiates _ that results in translation of new protein

second messenger kinase activity

when happens when dendrites are isolated in looking for evidence of local protein synthesis?

This prevents the delivery to the stimulated synapses of new proteins that were the product of a genomic signaling cascade. But, stimulation delivered to the Schaffer collateral fibers can produce a relatively long-lasting LTP.

what does L-LTP depend on (conclusion of the Bradshaw experiment)?

local dendritic translation

What happened in the Bradshaw experiment?

By stimulating one set of Schaffer collateral fibers they could produce L-LTP in synapses located on dendrites in the apical region of the neuron. By stimulating another set of Schaffer collaterals they could produce L-LTP in synapses located on dendrites in the basal region of the neuron. When the protein synthesis inhibitory emetine was applied to the entire slice, it prevented L-LTP in both dendritic fields. However, when emetine was applied to just the apical dendrites, it blocked L-LTP only in those dendrites, and when applied to just the basal dendrites, it blocked L-LTP only in the basal dendrites. It did not block L-LTP in either region of the dendrites when it was applied to just the soma. These results mean that L-LTP depended on proteins that were translated in the dendrites in response to the LTP-inducing stimulus.

Genomic signaling can occur via two pathways: __________ and __________.?

synapse to nucleus and soma to nucleus

which signaling model assumes that, as a result of action potentials produced by synaptic activity, Ca2+ enters the soma through voltage-dependent calcium channels where it can more directly initiate transcription?

soma to nucleus

which signaling model assumes that synaptic activity initiates a cascade that produces signaling molecules that eventually translocate to the nucleus to initiate transcription?

synapse to nucleus

for both genomic signaling cascades regulation of _ via _

transcription factor CREB via phosphorylation

what do ribosomes do?

translate mRNA into protein

when is synapse to nucleus signaling produced?

when second messenger kinase signaling cascades initiated in the dendritic spine compartment translocate to the nucleus to activate TFs such as CREB that target genes need for enduring LTP

Dudek and Fields Experiment: Weak stimulation produced only a _, but when it was followed by _ L-LTP was induced.

short lasting LTP, antidromic stimulation

LTP has two waves of _ that may result from strong high-frequency stimulation

protein synthesis

where do the two waves of protein synthesis occur?

The first wave occurs locally in the dendrites. The second wave occurs when new protein is synthesized from the new mRNA produced by the genomic signaling cascade. These proteins could be subsequently translated in either the soma or dendritic regions.

translating proteins requires increased _ levels

calcium

two general sources of calcium that influence LTP

calcium in the extracellular fluid surrounding the neuron and intracellular calcium stored in the smooth ER

how does extracellular calcium enter the cel/

it can enter a dendritic spine through NMDA receptors and can enter the soma through voltage dependent calcium channels

how is intracellular calcium stored on the smooth ER released?

it can be released into dendritic spines when Ca2+ binds to RyRs located in spines, or can be released into dendrites when IP3 binds to IP3Rs in the dendrite

_ are located on ER in dendritic spines and mediate calcium dependent calcium release

rynodine receptors

calcium induced calcium release (CICR) may contribute to some of the *_* to _

post-translational effects to induce LTP

_ are present on smooth ER in dendritic compartment

IP3 receptors

IP3 receptors release _ when activated by the _

calcium when activated by the second messenger IP3

_ mediate the synthesis of IP3

metabotropic glutamate receptors

metabotropic receptors are coupled to _ and can activate _

G-proteins and can activate second messengers

recruiting multiple _ increases the duration of LTP

calcium sources

the more calcium sources engaged, the more _ that increase stability and _ that support LTP

transcription and translation processes that increase the stability and consolidation of synaptic changes that support LTP

LTP1 depends only on RyRs releasing _ in the _ compartment

ER calcium in the dendritic spine compartment

LTP2 depends on _ activation and _ activation, so that IP3 receptors will release calcium from ER in the dendritic compartment

metabotropic GluR1 activation and IP3 SM activation

LTP3 depends on _ through vdCCs

calcium entering the soma through vdCCs

What two general processes are necessary for memory consolidation?

Translation and transcription

According to the *de novo* protein synthesis (DNPS) hypothesis long lasting memories require that the learning experience generate new proteins (t/f).

true

To ensure consolidation must be generated.

new proteins

Which of the following observations support the idea that the fundamental consolidating event is the construction of an enlarged stable spine?

a. inhibiting NMDA receptors prevent LTP induction

b. preventing actin polymerization prevents LTP from enduring

c. preventing cofilin phosphorylation prevents LTP from enduring

d. inhibiting actin polymerization prevents the generation of LTP

b and c

In the soma-to-nucleus cascade, __________ are assumed to open __________.

repetitive action potentials, voltage-dependent calcium channels (vdCCs)

To ensure a consolidated memory the __________ must initiate translation processes to generate new protein.

inducing stimulus

The consolidated outcome is likely the building of an _.

enlarged stable actin cytoskeleton

Why has anisomycin been used to study LTP?

Anisomycin is a general protein synthesis inhibitor. It is used to test the *de novo* protein synthesis hypothesis.

Why is emetine important?

It is the protein synthesis inhibitor Bradshaw and Bliss used to implicate local protein synthesis in the generation of long-lasting LTP.

Anisomycin causes LTP produced by intense, high-frequency stimulation to resemble LPT produced by a weak-induction stimulus (t/f).

true

Where is mRNA found in the neuron (three)?

nucleus, soma, and dendrites

Calcium dependent calcium release refers to extracellular calcium entering the cell (t/f).

false

Provide experimental support for the soma-to-nucleus model.

S-LTP can be converted into L-LTP by initiating action potentials without strongly stimulating synapses. First, CA1 neurons are weakly stimulated and then action potentials are initiated in the same CA1 cells antidromically. These action potentials alone also were sufficient to phosphorylate ERK and CREB protein.

Pretreatment with __________, a protein synthesis inhibitor, prevents the strong stimulus from producing L-LTP.

anisomycin

Which of the following is true?

a. transcription depends on post-translation modifications

b. transcription directly produces new proteins

c. genomic signaling can be initiated by synaptic activity

d. transcription processes generate mRNA

\

a, c, d

The __________ hypothesis is supported by experiments that separate dendrites in the CA1 region of the hippocampus from their cell bodies.

local protein synthesis

The synapse-to-nucleus hypothesis proposes that

a. genomic signaling is initiated directly in the synapse

b. genomic signaling molecules translocate from the synapse to the nucleus

c. genomic signaling is the result of calcium entering the soma from voltage depend calcium channels

d. all of the above

e. none of the above

a, b

The fact that anisomycin has no effect on short-lasting LTP implies that it require new protein to be generated (t/f)

false

Applying a protein synthesis inhibitor to the slice prior to LTP induction would _______?

prevent LTP from enduring

Local protein synthesis depends on _ mRNA.

already existing

The first of the two waves of protein synthesis depends on genomic signaling (t/f).

false

What is the major assumption in the soma-to-nucleus signaling model?

action potentials produced when a cell depolarizes open voltage dependent calcium channels near the soma that signal the nucleus

what is IP3 regulated by?

mGluRs

Name the two receptors that can release calcium from the ER into the dendritic compartment. What do they bind to?

\-IP3Rs, which respond to the second messenger IP3

\-RyRs, which bind to calcium

Transcription refers to the creation of new protein (t/f).

false

Describe the *de novo* protein synthesis hypothesis.

New protein is synthesized by processes initiated by the inducing stimulus.

When the protein synthesis inhibitor emetine was applied to the entire hippocampal slice, it __________ L-LTP, but when applied to only the soma it __________ L-LTP.

prevented; did not block

Both transcription and translation depend on post-translation modifications of existing protein (t/f).

true

Describe the influence of the protein synthesis inhibitor on anisomycin on LTP.

Applying anisomycin prevents the strong stimulus from producing L-LTP but leaves S-LTP intact.

CREB is an important translation factor found in dendrites (t/f).

false

Give two reasons why the ER is important in the context of synaptic plasticity.

1) It is a calcium sink that can rapidly sequester or store free calcium ions

2) It is a calcium source that can release calcium ions in response to second messengers

Calcium dependent calcium release occurs when calcium entering via NMDA receptors binds to RyRs on the endoplasmic reticulum (t/f).

true

Which of the following statements about the protein synthesis inhibitor emetine is true?

a. when applied selectively to the soma of stimulated neurons, it did not influence LTP.

b. when applied selectively to the apical dendrites, it prevented LTP from enduring in those dendrites

c. when applied selectively to the basal dendrites, it did not influence LTP in those dendrites.

d. a and b

e. none of the above

a, b

What are the calcium sources important for LTP?

enters the dendritic spines through NMDA receptors and enters the soma through vdCCs. The other source is intracellular Ca2+ stored in the ER. It can be released when calcium binds to the RyRs located on the ER in the spine or when IP3 binds to IP3Rs located on ER in the dendrite.

To produce mRNA, signaling molecules enter the nucleus to phosphorylate transcription factors (t/f).

true

A strong stimulus initiates two rounds of protein synthesis; they are _?

1) local translation and 2) genomic signaling cascades that transcribe new mRNA that can then be translated.

Genomic signaling refers to processes initiated by synaptic events that lead to the transcription of new mRNA (t/f).

true

Which of the following statements are true?

a.  calcium can be released from the endoplasmic reticulum.

b.  NMDA receptors are located on the endoplasmic reticulum.

c.  IP3 receptors are located primarily on endoplasmic reticulum in the dendritic region

d.  RYRs are located primarily on endoplasmic reticulum protruding into the spine.

a, c, d

Describe the order of events in the synapse-to-nucleus signaling model.

1) the stimulation of a postsynaptic neuron first activates second messengers, which 2) can then activate protein kinases, which 3) can translocate into the cell nucleus where 4) they can phosphorylate CREB protein, and transcription is initiated.

Dendritic protein synthesis (local protein synthesis) is not sufficient to produce relatively long lasting LTP (t/f).

false

Type: MR \n Which of the following statements is true?

a. Ionotropic receptors respond faster than metabotropic receptors.

b. Only NMDA receptors influx calcium.

c. NMDA receptors have an ion channel.

d. mGluRs have an ion channel.

a

Why is the activation of CREB a post-translation modification?

Because it is a protein and is activated when phosphorylated.

Which of the following statements about LTP is true?

a. S-LTP depends solely of post-translation modifications.

b. L-LTP depends on transcription and translation processes.

c. L-LTP depends on post translation modifications, transcription, and translation processes.

d. all of the above

d

Why does separating the dendrites from the soma provide evidence for local protein synthesis?

If the dendrites are separated from the soma, there is no way synaptic activity can signal the nucleus and no way for new plasticity products generated in the nucleus to reach the stimulated synapse.

The basic claim of the *de novo* protein synthesis hypothesis is that _?

memory consolidation depends on the learning experience generating new protein

Synapse-to-nucleus signaling but not soma-to-nucleus signaling depends on voltage gated calcium channels (t/f).

false

What is a major feature of the genomic signaling hypothesis?

It assumes that transcripts (mRNA) needed to sustain LTP are produced as a direct consequence of neural activity associated with the stimulus that induces LTP.

__________ produced by the weak stimulus depends only on __________ and __________ of existing protein.

S-LTP; post-translation modifications; rearrangements

What two major findings illustrate the important role local protein synthesis plays in L-LTP?

1) Stimulation delivered to the Schaffer collateral fibers can produce a relatively long-lasting LTP in dendrites separated from the soma.

2) Emetine selectively delivered to the soma does not influence L-LTP.

NMDA receptors and voltage gated calcium channels allow extracellular calcium to enter the neuron (t/f).

true

The presence of translation machinery and mRNA in the local dendritic region supports __________.

local protein synthesis

If the IP3 receptor is antagonized a short lasting LTP1 can still be produced (t/f).

true

What are plasticity products (PPs)?

The new mRNA and protein generated as a result of neural activity.

Calcium induced calcium release depends on _?

 calcium entering the spine via NMDA receptors binding to ryanodine receptors and the release of calcium from the endoplasmic reticulum

Metabotropic glutamate receptors have ion channels

false

Antidromic stimulation can convert a short-lasting LTP produced by a weak induction into a long-lasting LTP (t/f).

true

What is calcium-induced calcium release (CICR)?

The ER that protrudes into the spine contains ryanodine receptors (RyRs), which bind to calcium entering through NMDA receptors. Thus extracellular Ca2+ is amplified and some of the post-translation modifications necessary to induce LTP are triggered.

Which of the following can be found in the dendritic region?

a. Endoplasmic reticulum and golgi elements

b. Transcription factors, ribosomal assemblies, and mRNAs

c. Ribosomal assemblies and mRNAs

d. Golgi elements

 a, c

Extracellular Ca2+ can enter a dendritic spine through __________ and can enter the soma through __________.

NMDA receptors; vdCCs

The idea that synaptic activity leads to the transcription of new plasticity product needed to build long-lasting LTP is called the _?

genomic signaling hypothesis