Molecular mechanisms of learning and memory

Question 1

According to Hebb, what can result in memories? Why did Eric Kandel and other researchers study invertebrate animals for insights into the molecular mechanisms of memory?

Answer 1

-Memories can result from subtle alterations in synapses.
- Invertebrates have small nervous systems with large neurons, known and reproducible connections between neurons, and simple genetics, making them useful for studying memory mechanisms.

Question 2

What is one approach used to study memory mechanisms?

Answer 2

Electrical brain stimulation to produce measurable synaptic alterations, whose mechanisms can be studied and compared to natural memory formation.

Question 3

What are the two stages of memory processing?

Answer 3

1) Acquisition of short-term memory, and 2) Consolidation of long-term memory.

Question 4

How does memory acquisition (learning) occur?

Answer 4

Memory acquisition is a physical modification of the brain caused by incoming sensory information.

Question 5

What is the key difference between working memory and short-term memory?

Answer 5

Working memory relies on continuous rehearsal and doesn’t require lasting physical changes in the brain, while short-term memory can survive distractions, has a larger capacity, and can last minutes to hours without conscious effort.

Question 6

What is memory consolidation?

Answer 6

Memory consolidation is the process of selecting some experiences held temporarily by transient modifications of neurons for permanent storage in long-term memory.

Question 7

How is acquisition of short-term memory achieved?

Answer 7

Memory acquisition occurs by modifying synaptic transmission between neurons.

Question 8

What is necessary for synaptic consolidation in memory processing?

Answer 8

In addition to modifying synaptic transmission, synaptic consolidation requires new gene expression and protein synthesis.

Question 9

What is the cellular activity like when it comes to memory?

Answer 9

While it might appear that a person is doing nothing, at the cellular level, they are quite busy, with virtually every neuron in the nervous system capable of forming a memory of recent patterns of activity.

Question 10

Where are declarative memories (facts, events, places, faces) ultimately stored?

Answer 10

Declarative memories are ultimately stored in the cerebral cortex.

Question 11

How does the localization of an engram work?

Answer 11

If an engram is based on information from only one sensory modality, it should be possible to localize it within the regions of cortex that serve this modality.

Question 12

What happens to an IT (inferior temporal cortex) neuron as a visual recognition memory is formed for new faces?

Answer 12

The first time new faces are seen, the cell responds at about the same moderate level to all of them, but with repeated presentations, the responses change and selectivity emerges. The response of the neuron grows to some faces and diminishes to others.

Question 13

What do shifts in the selectivity of cortical neurons indicate in terms of memory formation?

Answer 13

Shifts in the selectivity of cortical neurons are a common cellular correlate of memories formed in various sensory modalities, suggesting the formation of a memory trace.

Question 14

What is the neural basis for an experience-dependent shift in neuronal selectivity?

Answer 14

The neural basis for an experience-dependent shift in neuronal selectivity involves adjustments in the strength or “weights” of synaptic inputs converging on cortical neurons. This adjustment results in unique patterns of activity in neurons for familiar stimuli, creating distributed memory.

Question 15

How does a distributed memory differ from a memory encoded solely by one neuron?

Answer 15

In a distributed memory, no single neuron represents a memory; instead, memories are represented by patterns of activity across multiple neurons. This approach makes memories more resistant to damage to individual neurons and enables the storage of numerous unique memories.

Question 16

What is graceful degradation in the context of memory loss?

Answer 16

Graceful degradation is a type of memory loss where, instead of a catastrophic loss of a specific memory, representations tend to blend together as neurons are lost. This occurs when neurons are gradually removed, such as in old age or due to brain disease.

Question 17

What experimental support did Eric Kandel’s studies provide for the synaptic basis of memory?

Answer 17

Eric Kandel’s studies on the marine snail Aplysia showed that simple forms of learning, such as habituation and sensitization, were accompanied by changes in the strength of synaptic transmission between sensory neurons and motor neurons. These studies supported the idea that synaptic modifications are the basis of memory storage.

Question 18

what did Eric Kandel early studies on Aplysia reveal about short-term memory? How is long-term memory different from short-term memory in Aplysia? What did the author’s studies suggest about memory storage in Aplysia?

Answer 18

-It results from a transient strengthening of preexisting synaptic connections due to the modification of preexisting proteins.
-Long-term memory results from a persistent strengthening of synaptic connections brought about by alterations in gene expression, the synthesis of new proteins, and the growth of new synaptic connections.
-Memory appears to be distributed among multiple sites, and a single synaptic connection is capable of being modified in opposite ways by different forms of learning and for different periods of time.

Question 19

What is long-term potentiation (LTP)? Where was long-term potentiation (LTP) originally discovered? How does synaptic plasticity occur in neural networks?

Answer 19

-Long-term potentiation (LTP) is a neural process that involves the strengthening of synaptic connections between neurons, often associated with memory formation.
-LTP was originally discovered in the hippocampus, a brain region critical for memory formation.
-Both increases and decreases in synaptic weights can shift neuronal selectivity and store information within neural network models.

Question 20

What are the two thin sheets of neurons in the hippocampus? What are the two divisions of Ammon’s horn focused on in this discussion?

Answer 20

The two thin sheets of neurons in the hippocampus are the dentate gyrus and Ammon’s horn. we focus on two divisions of Ammon’s horn: CA3 and CA1

Question 21

What is the major input to the hippocampus, and how does it send information?

Answer 21

The major input to the hippocampus is the entorhinal cortex, and it sends information to the hippocampus through a bundle of axons called the perforant path.

Question 22

What are the three sets of synaptic connections involved in the hippocampal trisynaptic circuit?

Answer 22

The three sets of synaptic connections involved in the hippocampal trisynaptic circuit are:

1. Entorhinal cortex → dentate gyrus (perforant path) synapses.
2. Dentate gyrus → CA3 (mossy fiber) synapses.
3. CA3 → CA1 (Schaffer collateral) synapses

Question 23

What did Timothy Bliss and Terje Lømo discover in the hippocampus in 1973?

Answer 23

They found that brief, high-frequency electrical stimulation of the perforant path synapses on the neurons of the dentate gyrus produced LTP.

Question 24

How is the effectiveness of the Schaffer collateral synapse typically monitored in experiments?

Answer 24

It is monitored by giving a bundle of presynaptic axons a brief electrical stimulus, then measuring the size of the resulting EPSP in a postsynaptic CA1 neuron.

Question 25

What is input specificity in the context of LTP?

Answer 25

Input specificity means that only the active inputs show the synaptic plasticity, and synapses that did not receive tetanic stimulation do not show LTP.

Question 26

What is cooperativity in the context of LTP? How can cooperativity be related to forming associations?

Answer 26

-Cooperativity means that synapses must be active at the same time as the postsynaptic CA1 neuron is strongly depolarized to induce LTP, requiring both temporal and spatial summation of EPSPs.
-Cooperativity can lead to the formation of associations by causing the potentiation of synapses that are active together, thereby associating specific inputs that fire simultaneously.

Question 27

Is LTP in CA1 Hebbian or non-Hebbian?

Answer 27

LTP in CA1 is Hebbian, meaning that inputs that fire together wire together, consistent with the idea of Hebbian synapses

Question 28

What is the neurotransmitter responsible for excitatory synaptic transmission in the hippocampus?

Answer 28

Glutamate

Question 29

Which subclass of glutamate receptors mediates excitatory postsynaptic potentials (EPSPs) at the Schaffer collateral-CA1 pyramidal cell synapse?

Answer 29

AMPA receptors

Question 30

What unique property do NMDA receptors have in relation to ion conduction?

Answer 30

NMDA receptors conduct Ca²⁺ ions only when glutamate binds and the postsynaptic membrane is depolarized enough to displace Mg²⁺ ions that clog the channel.

Question 31

How is the induction of long-term potentiation (LTP) related to the rise in postsynaptic [Ca²⁺]ᵢ?

Answer 31

The rise in postsynaptic [Ca²⁺]ᵢ is linked to the induction of LTP, and inhibiting NMDA receptors or preventing rises in postsynaptic [Ca²⁺]ᵢ can prevent LTP induction.

Question 32

What are the two protein kinases activated by the rise in postsynaptic [Ca²⁺]ᵢ following NMDA receptor activation?

Answer 32

The two protein kinases activated are protein kinase C and calcium-calmodulin-dependent protein kinase II (CaMKII).

Question 33

How does phosphorylation of the AMPA receptor affect its function?

Answer 33

Phosphorylation of the AMPA receptor, by protein kinase C or CaMKII, increases the ionic conductance of the channel, making it more effective.

Question 34

What is the possible outcome of the activation of CaMKII in relation to AMPA receptors?

Answer 34

Activation of CaMKII may lead to the insertion of entirely new AMPA receptors into the postsynaptic membrane.

Question 35

How does the addition of new membrane affect postsynaptic dendritic spines following LTP?

Answer 35

The addition of new membrane causes the spines to swell, and synaptic structure changes include the formation of new synaptic contacts with axons.

Question 36

What effect does synaptic structure changes following LTP have on the probability of action potentials triggering presynaptic glutamate release?

Answer 36

Synaptic structure changes, including the formation of multiple synapses on the same postsynaptic neuron, increase the probability that an action potential in the axon will trigger presynaptic glutamate release.

Question 37

What was the key assumption of the BCM theory regarding synaptic weakening?

Answer 37

The BCM theory assumed that synapses would undergo synaptic weakening instead of long-term potentiation (LTP) when they are active at the same time the postsynaptic cell is only weakly depolarized by other inputs.

Question 38

What is homosynaptic long-term depression (LTD)?

Answer 38

Homosynaptic long-term depression (LTD) is a form of synaptic plasticity where synaptic transmission occurring at the same time as weak or modest depolarization of the postsynaptic neuron causes LTD of the active synapses.

Question 39

What are the two simple rules governing bidirectional plasticity of many cortical synapses?

Answer 39

1. Synaptic transmission occurring at the same time as strong depolarization of the postsynaptic neuron causes long-term potentiation (LTP) of the active synapses.
2. Synaptic transmission occurring at the same time as weak or modest depolarization of the postsynaptic neuron causes long-term depression (LTD) of the active synapses.

Question 40

in the context of spike timing–dependent plasticity, what happens when the EPSP caused by synaptic glutamate release precedes an action potential in the postsynaptic neuron?

Answer 40

In spike timing–dependent plasticity, long-term potentiation (LTP) can result when the EPSP caused by synaptic glutamate release precedes an action potential in the postsynaptic neuron.

Question 41

In many cortical synapses, what is the outcome when the EPSP caused by glutamate release follows a postsynaptic action potential?

Answer 41

When the EPSP follows a postsynaptic action potential:

-If the EPSP arrives during the rising phase of the action potential, it can amplify the action potential.
-If it arrives during the falling phase, it’s less likely to affect the action potential significantly. Timing is crucial for impact. This is known as temporal summation and plays a role in information processing in the cortex.

Question 42

What is the role of NMDA receptors?

Answer 42

NMDA receptors allow calcium ions (Ca²⁺) to enter the postsynaptic neuron when activated.

Question 43

NMDA receptors allow calcium ions (Ca²⁺) to enter the postsynaptic neuron when activated.

Answer 43

They are a group of glutamate receptors that work through G-protein signaling mechanisms.

Question 44

What is the Mg²+ block in the context of NMDA receptors?

Answer 44

It is the blocking of NMDA receptor channels by magnesium ions (Mg²+), preventing the entry of calcium ions (Ca²⁺).

Question 45

What are AMPA receptors responsible for?

Answer 45

AMPA receptors are responsible for fast synaptic transmission in the central nervous system.

Question 46

What is the internalization of AMPA receptors?

Answer 46

It is the process of bringing AMPA receptors back into the neuron, reducing their presence at the synapse.

Question 47

What are the two forms of homosynaptic LTD at Schaffer
collateral–CA1 synapse:

Answer 47

–G-protein coupled metabotropic glutamate
receptors (mGluRs)
–NMDA receptors
*Rise in postsynaptic [Ca2+] is necessary to
trigger LTD

Question 48

does LTP and LTD have bidirectional regulation?

Answer 48

yes

Question 49

What is continuously happening with AMPA receptors in the postsynaptic membrane?

Answer 49

AMPA receptors are continually being added and removed, even in the absence of synaptic activity.

Question 50

How often are synaptic AMPA receptors estimated to be replaced? What is the key to stable synaptic transmission despite the continuous turnover of AMPA receptors?

Answer 50

-Researchers estimate that half of the synaptic AMPA receptors are replaced every 15 minutes.
-As long as one receptor is added whenever one receptor is removed, synaptic transmission remains stable.

Question 51

What determines the capacity of the postsynaptic membrane for AMPA receptors?

Answer 51

The capacity is determined by the size of a scaffold made up of slot proteins, similar to an egg carton.

Question 52

How does stable LTP affect the capacity of the synaptic membrane for AMPA receptors?

Answer 52

Stable LTP increases the capacity by increasing the size of the “egg carton” and providing new “eggs.”

Question 53

What is believed to be the “egg carton” in the synaptic membrane?

Answer 53

PSD-95 (postsynaptic density protein with a molecular weight of 95 kilodaltons) is believed to comprise the “egg carton.”

Question 54

How does LTP selectively increase the number of AMPA receptors?

Answer 54

LTP can selectively increase the number of GluR1-containing AMPA receptors in the membrane.

Question 55

What happens to the GluR1-containing AMPA receptors over time?

Answer 55

Over time, these receptors are replaced by those that lack GluR1.

Question 56

What is necessary for stable LTD?

Answer 56

Stable LTD requires reducing the size of the “egg carton,” which reduces the capacity for “eggs.”

Question 57

What occurs during LTD-inducing stimulation?

Answer 57

During LTD-inducing stimulation, there is both destruction of PSD-95 and a net loss of AMPA receptors from the postsynaptic membrane.

Question 58

Where in the brain is NMDA receptor-dependent synaptic plasticity, similar to LTP and LTD in the hippocampus, also found?

Answer 58

Recent research indicates that these mechanisms occur throughout the neocortex, including area IT, where memories of familiar faces are created.

Question 59

How does inhibitory avoidance learning relate to the study of LTP and LTD? (morris experiments)

Answer 59

Inhibitory avoidance learning is a robust type of learning that allowed researchers to observe changes in synaptic transmission at Schaffer collateral–CA1 synapses, including the induction of LTP.

Question 60

What role do NMDA receptors play in learning and memory?

Answer 60

NMDA receptors are involved in both synaptic plasticity (LTP and LTD) and learning. Blocking NMDA receptors in the hippocampus prevents the formation of aversive memories.

Question 61

How did researchers manipulate genes in mice to study the molecular basis of learning? What limitations are associated with genetic approaches to studying learning and memory? (tonegawa, silva experiment)

Answer 61

-Researchers “knocked out” (deleted) specific genes in mice to assess their role in LTP, LTD, and memory formation.
-Genetic manipulations may have secondary consequences or affect multiple cell types. It can be challenging to pinpoint the exact contribution of a molecule to learning.

Question 62

What is the role of CA1 NMDA receptors in learning and memory?

Answer 62

CA1 NMDA receptors in the hippocampus are essential for various forms of learning, as shown by genetic studies in mice.

Question 63

How do animals with an increased number of NMDA receptors perform in learning tasks?

Answer 63

Animals engineered to produce more NMDA receptors than normal often show enhanced learning ability in certain tasks.

Question 64

What is homeostasis in the context of synaptic plasticity? Why is homeostasis important in synaptic plasticity?

Answer 64

-Homeostasis refers to regulatory mechanisms that maintain the stability of synaptic weights within a useful dynamic range, preventing synapses from becoming too strong or too weak.
-Homeostasis is essential to ensure that synaptic plasticity remains balanced, allowing for stable and reliable neuronal responses while still allowing for learning and memory processes.

Question 65

What does weak NMDA receptor activation cause? What does strong NMDA receptor activation cause?

Answer 65

-LTD
-LTP

Question 66

What is the synaptic modification threshold?

Answer 66

It is the level of moderate NMDA receptor activation between that required for LTD and for LTP where there is no net change.

Question 67

What is the BCM theory?

Answer 67

It’s a theory proposing that the modification threshold adjusts based on the history of integrated postsynaptic activity.

Question 68

How does the modification threshold change with increased activity? How does the modification threshold change with decreased activity?

Answer 68

-It slides up, making LTP more difficult to produce.
-It slides down, making LTD less likely and LTP easier to produce.

Question 69

What is metaplasticity?

Answer 69

it’s the concept that synaptic plasticity rules change based on the history of synaptic or cellular activity.

Question 70

How are NMDA receptor subunit composition changes related to metaplasticity?

Answer 70

Adjustments in the molecular composition of NMDA receptors, particularly the ratio of NR2A to NR2B subunits, influence synaptic plasticity. Higher NR2B levels favor LTP, while higher NR2A levels favor LTD.

Question 71

How do changes in NMDA receptor subunit composition occur?

Answer 71

They occur relatively slowly over hours, likely involving the synthesis of new protein subunits.

Question 72

What are the two inputs received by Purkinje cells in the cerebellar cortex?

Answer 72

Purkinje cells receive inputs from climbing fibers and parallel fibers.

Question 73

What is the role of the climbing fiber input to Purkinje cells?

Answer 73

The climbing fiber input carries error signals indicating a movement has failed to meet expectations.

Question 74

How is motor learning theorized to occur in the cerebellar cortex according to David Marr’s proposal?

Answer 74

Motor learning occurs by adjusting the effectiveness of parallel fiber inputs to Purkinje cells based on error signals from climbing fiber inputs.

Question 75

What is LTD, and how is it induced in the cerebellar cortex?

Answer 75

LTD (Long-Term Depression) is a form of synaptic plasticity. In the cerebellar cortex, LTD is induced by a conjunction of a large surge in postsynaptic [Ca2+] from climbing fiber activation and the activation of metabotropic glutamate receptor 1 (mGluR1) by parallel fibers.

Question 76

Describe another form of LTD in the nucleus accumbens.

Answer 76

In the nucleus accumbens, activation of postsynaptic mGluR5 stimulates the synthesis of endocannabinoids, which cause a persistent depression of glutamate release, leading to LTD.

Question 77

What timing requirement is necessary for LTD in neocortical pyramidal neurons?

Answer 77

LTD in neocortical pyramidal neurons is induced when a postsynaptic spike (causing the release of endocannabinoids) precedes the presynaptic spike by a few tens of milliseconds.

Question 78

How do different mechanisms for LTD affect synaptic plasticity in the brain?

Answer 78

Different mechanisms for LTD impose various rules on the patterns of activity that yield synaptic plasticity, optimizing their contribution to the functions of different brain circuits.

Question 79

What is denervation supersensitivity, and how was it demonstrated by Walter Cannon?

Answer 79

Denervation supersensitivity is the increased electrical excitability and sensitivity of a muscle to the neurotransmitter acetylcholine (ACh) following the cutting of a nerve to that muscle. Walter Cannon demonstrated this phenomenon through experiments in the 1930s.

Question 80

What causes denervation supersensitivity in neurons other than nerve cutting?

Answer 80

Denervation supersensitivity can also occur when neurotransmitter receptors are pharmacologically blocked or when muscles or neurons are electrically silenced with tetrodotoxin (TTX).

Question 81

How do cortical neurons respond to overall changes in synaptic input, and what is this adjustment called?

Answer 81

When cortical neurons experience changes in overall synaptic input, their electrical excitability and the strength of excitatory synapses increase. This adjustment of absolute synaptic effectiveness that preserves the relative distribution of synaptic weights is called synaptic scaling.

Question 82

What does synaptic scaling involve in terms of changing synaptic strengths?

Answer 82

Synaptic scaling involves adjusting the values of all synaptic weights by the same factor, either increasing or decreasing them while preserving their relative differences.

Question 83

What mechanisms contribute to synaptic scaling, and over what time period does it occur?

Answer 83

Multiple mechanisms contribute to synaptic scaling, with one involving calcium (Ca2+) entry into the soma through voltage-gated Ca2+ channels and activation of calcium-calmodulin-dependent kinase IV (CaMKIV). Synaptic scaling occurs over a longer time period (hours to days) compared to the induction of LTP or LTD (seconds to minutes). This extended time is necessary for adjusting the strengths of numerous synapses.

Question 84

What role do metaplasticity and scaling play in maintaining neuronal function and plasticity?

Answer 84

Metaplasticity and scaling mechanisms help maintain the balance between synaptic plasticity and stability. They ensure that synaptic changes are appropriately adjusted based on the level of neuronal activity, promoting both LTD and LTP as needed for proper function, experience-dependent shifts in selectivity, and learning and memory

Question 85

What is the initial modification in synaptic transmission that can result in memory formation?

Answer 85

The initial modification in synaptic transmission that can result in memory formation is changing the number of phosphate groups attached to proteins in the synaptic membrane.

Question 86

Why is phosphorylation as a long-term memory consolidation mechanism problematic?

Answer 86

Phosphorylation is problematic for long-term memory consolidation because:

1. Phosphate groups are not permanent and can be removed over time, erasing the memory.
2. Most brain proteins have a short lifespan, less than 2 weeks, which makes memories tied to individual protein changes unlikely to survive.

Question 87

What is needed to convert changes in synaptic protein phosphorylation into a form of memory that can last a lifetime?

Answer 87

Mechanisms are needed to convert changes in synaptic protein phosphorylation into a form of memory that can last a lifetime.

Question 88

How are kinase enzymes normally regulated in the brain?

Answer 88

Kinase enzymes are typically regulated and turned “on” only in the presence of a second messenger.

Question 89

What happens to the CaMKII kinase during long-term potentiation (LTP) in the hippocampus?

Answer 89

CaMKII kinase stays “on” for an extended period after the calcium levels have returned to a low level following LTP induction.

Question 90

What is the autophosphorylation of CaMKII, and how does it relate to its persistent activity?

Answer 90

Autophosphorylation is a process where each subunit of CaMKII phosphorylates a neighboring subunit, which keeps the kinase active by preventing the hinge from closing.

Question 91

What is the molecular switch hypothesis, and how does it relate to synaptic potentiation?

Answer 91

The molecular switch hypothesis suggests that autophosphorylating kinases, like CaMKII, can store information at the synapse and contribute to the maintenance of synaptic potentiation.

Question 92

What is the role of protein kinase M zeta (PKMς) in maintaining LTP and memories?

Answer 92

PKMς plays a role in maintaining LTP and certain memories, and its persistent activity contributes to changes in synaptic strength.

Question 93

How does the small peptide ZIP affect PKMς and memories?

Answer 93

ZIP, when injected intracerebrally, inhibits PKMς and can erase LTP and memories that were established days before the injection.

Question 94

What is the current model for how PKMς becomes persistently active in response to synaptic activity?

Answer 94

The model suggests that strong synaptic activation triggers the synthesis of new PKMς molecules, which then phosphorylate synaptic proteins involved in regulating AMPA receptor number and mRNA translation at the synapse.

Question 95

What are the implications of ZIP’s effect on memory for our understanding of memory mechanisms?

Answer 95

ZIP’s ability to erase memories suggests that understanding how it works can provide insights into the mechanisms underlying memory processes.

Question 96

What is the relationship between protein synthesis and memory consolidation? How have researchers studied the role of protein synthesis in memory?

Answer 96

-Protein synthesis is important for memory consolidation, as inhibiting it can impair the formation of long-term memories.
-Researchers have used protein synthesis inhibitors injected into the brains of animals during or after training to assess the impact on learning and memory.

Question 97

What happens when protein synthesis is inhibited during memory consolidation?

Answer 97

When protein synthesis is inhibited during memory consolidation, short-term memories may form normally, but long-term memories are impaired.

Question 98

How does the timing of protein synthesis inhibition affect memory? Can you provide an example of a memory affected by protein synthesis inhibition?

Answer 98

-Memories become increasingly resistant to the inhibition of protein synthesis as the time interval between training and inhibitor injection is increased.
-Inhibitory avoidance memory, where a rat avoids a location where it received a foot shock, fades within a day if protein synthesis is inhibited shortly before training.

Question 99

What effect does inhibiting protein synthesis have on synaptic potentiation in the hippocampus?

Answer 99

Inhibiting protein synthesis at the time of a tetanus does not affect the induction of long-term potentiation (LTP) in the hippocampus, but the synaptic potentiation gradually disappears over a few hours instead of lasting days to months.

Question 100

How does memory formation initially involve synaptic proteins?

Answer 100

Memory formation involves the rapid modification of existing synaptic proteins, which counteracts factors that could erase a memory.

Question 101

What is the challenge in making synaptic changes and memories permanent?

Answer 101

The challenge is that memory modifications are temporary unless new proteins arrive at the modified synapses to convert the changes into more permanent ones.

Question 102

How do proteins required for consolidating synaptic changes and memories find the modified synapses?

Answer 102

Proteins required for consolidation find modified synapses through a tagging mechanism that allows them to bind to the synapses undergoing modifications.

Question 103

What did Julietta Frey and Richard Morris discover in their experiments regarding protein synthesis and synaptic tagging?

Answer 103

They found that newly synthesized proteins triggered by strong synaptic stimulation could also consolidate long-term potentiation (LTP) caused by weak synaptic stimulation, suggesting that the weak stimulation endows synapses with a temporary tag that captures the newly synthesized proteins.

Question 104

How long does the tagging mechanism last, according to Frey and Morris’s experiments?

Answer 104

The tagging mechanism lasts about 2 hours, allowing for the consolidation of synaptic changes and memories during that time frame.

Question 105

What molecular mechanisms are believed to be involved in synaptic tagging?

Answer 105

Phosphorylation of synaptic proteins by various kinases, including CaMKII and PKMς, is believed to be involved in synaptic tagging.

Question 106

What regulates the protein synthesis required for memory consolidation?

Answer 106

Transcription factors in the nucleus, such as CREB (cyclic AMP response element binding protein).
-CREB stands for cyclic AMP response element binding protein.

Question 107

How does CREB regulate gene expression?

Answer 107

CREB binds to specific DNA segments called CREs (cyclic AMP response elements) and either activates or represses neighboring gene expression, depending on its phosphorylation state.

Question 108

What did the study by Tim Tully and Jerry Yin in 1994 show about CREB?

Answer 108

The study showed that CREB regulates the gene expression required for memory consolidation in the fruit fly Drosophila melanogaster.

Question 109

What effect does overexpressing CREB-2 have on memory consolidation in flies?

Answer 109

Overexpressing CREB-2 represses gene expression regulated by CREs and blocks memory consolidation in flies

Question 110

What effect does overexpressing CREB-1 have on memory in flies?

Answer 110

Overexpressing CREB-1 enhances memory in flies, allowing them to remember tasks after a single training trial.

Question 111

What is the significance of CREB in memory consolidation in various species, including mice?

Answer 111

CREB has been implicated in regulating the consolidation of sensitization in Aplysia, as well as long-term potentiation and spatial memory in mice.

Question 112

How does modulation of gene expression by CREB affect memory strength?

Answer 112

Modulation of gene expression by CREB provides a molecular mechanism to control the strength of a memory.

Question 113

What are the potential applications of memory-enhancing drugs related to CREB?

Answer 113

Memory-enhancing drugs targeting CREB could benefit individuals with brain disorders and aging-related memory issues. However, their ethical use in healthy individuals is a subject of debate.

Question 114

What challenges have prevented the development of memory-enhancing drugs targeting CREB?

Answer 114

While compounds that enhance memory consolidation have been discovered, their side effects have hindered their development into drugs.

Question 115

How does the synapse utilize the timing of gene expression and the arrival of a new protein for memory formation?

Answer 115

One possibility is that newly synthesized proteins, like PKMς, trigger local synaptic protein synthesis to maintain a synaptic change.

Question 117

What happens to the number of synapses per neuron in the occipital cortex of rats placed in a “complex” environment?

Answer 117

Placing rats in a complex environment with toys and playmates increases the number of synapses per neuron in the occipital cortex by about 25%.

Question 118

What does recent research using microscopy and cell labeling methods reveal about structural changes in neurons in response to altered environments?

Answer 118

Altering the visual or tactile environment stimulates the formation of new dendritic spines and the growth of new synapses, consistent with the mechanisms of long-term potentiation (LTP) and long-term depression (LTD) that encode memory.

Question 119

What are the limitations to structural plasticity in the adult brain

Answer 119

Large changes in brain circuitry are generally confined to critical periods of early life, and most axons in the adult central nervous system have restricted growth and retraction. However, changes in the structure of axon terminals and synaptic effectiveness can still occur in adulthood.