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Questions and Answers
What is the function of the liquid-liquid phase separation of CaMKII, as mentioned in the content?
What is the function of the liquid-liquid phase separation of CaMKII, as mentioned in the content?
- It is a mechanism used to trigger the expression phase of LTP.
- It is a novel mechanism involved in Long-Term Potentiation (LTP). (correct)
- It is involved in the induction phase of LTP.
- It controls the maintenance phase of LTP.
Which of the following is a step involved in LTP as discussed in the text?
Which of the following is a step involved in LTP as discussed in the text?
- Maintenance (correct)
- Inversion
- Suppression
- Repression
What does the term "induction" refer to in the context of LTP?
What does the term "induction" refer to in the context of LTP?
- The long-term strengthening of synaptic connections.
- The process by which a signal activates cellular signaling pathways. (correct)
- The maintenance of the strengthened synaptic connections.
- The immediate changes that occur at the synapse.
What is the primary focus of the book referenced by the author in 1949?
What is the primary focus of the book referenced by the author in 1949?
What is the proposed mechanism by which Hebb's model explains learning and memory?
What is the proposed mechanism by which Hebb's model explains learning and memory?
What is the significance of the term "efficiency" as used in the context of Hebb's model?
What is the significance of the term "efficiency" as used in the context of Hebb's model?
What is the relationship between CaMKII and other effector proteins?
What is the relationship between CaMKII and other effector proteins?
What is the role of CaMKII in maintaining the strength of synaptic connections as discussed in the text?
What is the role of CaMKII in maintaining the strength of synaptic connections as discussed in the text?
Which study examined the impact of reduced NMDA receptor expression on mouse behavior?
Which study examined the impact of reduced NMDA receptor expression on mouse behavior?
What is the primary focus of the study by N.E. et al., 2014?
What is the primary focus of the study by N.E. et al., 2014?
Which study explored the role of GluR1 phosphorylation in synaptic plasticity?
Which study explored the role of GluR1 phosphorylation in synaptic plasticity?
What technique was used to create a probe for fluorescence lifetime imaging of CaMKII activity in the study by Kwok et al., 2008?
What technique was used to create a probe for fluorescence lifetime imaging of CaMKII activity in the study by Kwok et al., 2008?
In the context of synaptic plasticity, what does the study by Larkman et al., 1992, suggest about presynaptic release probability?
In the context of synaptic plasticity, what does the study by Larkman et al., 1992, suggest about presynaptic release probability?
According to the study by Miller et al., 1988, which receptors play a role in the induction and expression of long-term potentiation?
According to the study by Miller et al., 1988, which receptors play a role in the induction and expression of long-term potentiation?
The study by Miyawaki, 2005, focused on which aspect of brain function?
The study by Miyawaki, 2005, focused on which aspect of brain function?
Which study investigated the molecular basis of intellectual disability?
Which study investigated the molecular basis of intellectual disability?
Which of these is NOT a characteristic of Hebbian synaptic plasticity?
Which of these is NOT a characteristic of Hebbian synaptic plasticity?
What is the primary role of NMDA receptors in synaptic transmission?
What is the primary role of NMDA receptors in synaptic transmission?
Which of the following researchers conducted experiments that provided the first experimental demonstration of Hebbian plasticity in an animal?
Which of the following researchers conducted experiments that provided the first experimental demonstration of Hebbian plasticity in an animal?
Why is in vitro hippocampal slice preparation considered advantageous for studying LTP?
Why is in vitro hippocampal slice preparation considered advantageous for studying LTP?
What is the specific phenomenon that Hebbian plasticity refers to?
What is the specific phenomenon that Hebbian plasticity refers to?
What is the primary role of AMPA receptors in basal synaptic transmission?
What is the primary role of AMPA receptors in basal synaptic transmission?
Which of the following is NOT a mechanism that contributes to the maintenance of LTP?
Which of the following is NOT a mechanism that contributes to the maintenance of LTP?
What is the core concept behind the term “expression” in the context of Hebbian synaptic plasticity?
What is the core concept behind the term “expression” in the context of Hebbian synaptic plasticity?
What role does calcium/calmodulin-dependent protein kinase II play in neuron function?
What role does calcium/calmodulin-dependent protein kinase II play in neuron function?
What is the effect of repeated stress on cognitive function as suggested in the content?
What is the effect of repeated stress on cognitive function as suggested in the content?
What is a key finding related to nitric oxide and carbon monoxide regarding synaptic enhancement?
What is a key finding related to nitric oxide and carbon monoxide regarding synaptic enhancement?
Which of the following techniques is used to visualize synaptic calcium signaling in neurons?
Which of the following techniques is used to visualize synaptic calcium signaling in neurons?
What phenomenon occurs due to the alignment of trans-synaptic nanocolumns?
What phenomenon occurs due to the alignment of trans-synaptic nanocolumns?
What role does calcium/calmodulin-dependent kinase II play in synaptic plasticity?
What role does calcium/calmodulin-dependent kinase II play in synaptic plasticity?
Which factor is critical for AMPA receptor expression in hippocampal pyramidal neurons?
Which factor is critical for AMPA receptor expression in hippocampal pyramidal neurons?
What hypothesis suggests that specific synaptic events can 'tag' synapses for later potentiation?
What hypothesis suggests that specific synaptic events can 'tag' synapses for later potentiation?
What is the function of the Ras-like GTPase Rem2 in relation to calcium/calmodulin-dependent kinase II?
What is the function of the Ras-like GTPase Rem2 in relation to calcium/calmodulin-dependent kinase II?
Which process is directly revealed by analyzing miniature synaptic currents?
Which process is directly revealed by analyzing miniature synaptic currents?
What does the phosphorylation and regulation of glutamate receptors depend on?
What does the phosphorylation and regulation of glutamate receptors depend on?
Which of the following studies focused on the structural basis of long-term potentiation?
Which of the following studies focused on the structural basis of long-term potentiation?
What is one of the key findings from the study on postsynaptic contributions to long-term potentiation?
What is one of the key findings from the study on postsynaptic contributions to long-term potentiation?
What is one role of Ca2+/calmodulin-dependent protein kinase II in relation to synaptic activity?
What is one role of Ca2+/calmodulin-dependent protein kinase II in relation to synaptic activity?
What mechanism is suggested to underlie post-tetanic potentiation?
What mechanism is suggested to underlie post-tetanic potentiation?
Which process is examined in the context of cGMP's role in long-term potentiation?
Which process is examined in the context of cGMP's role in long-term potentiation?
What was identified adjacent to the inhibitory and calmodulin-binding domains of CaMKII?
What was identified adjacent to the inhibitory and calmodulin-binding domains of CaMKII?
Which neurotransmitter's transporter is affected by the blockade that potentiates postsynaptic excitation?
Which neurotransmitter's transporter is affected by the blockade that potentiates postsynaptic excitation?
What is the primary focus of the study by Shen et al. regarding CaMKII?
What is the primary focus of the study by Shen et al. regarding CaMKII?
What type of dependency does CaMKII exhibit in its functionality?
What type of dependency does CaMKII exhibit in its functionality?
What role does the study suggest for NMDA receptor stimulation in neurons?
What role does the study suggest for NMDA receptor stimulation in neurons?
Flashcards
Hebbian synaptic plasticity
Hebbian synaptic plasticity
A property of synapses that undergo changes during strengthened connections due to activation.
Tetanic stimulation
Tetanic stimulation
A brief, strong stimulation of synaptic input that can trigger changes in synaptic transmission.
Long-term potentiation (LTP)
Long-term potentiation (LTP)
A persistent increase in synaptic strength following high-frequency stimulation.
AMPA receptors
AMPA receptors
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NMDA receptors
NMDA receptors
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Expression of synaptic transmission
Expression of synaptic transmission
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Maintenance mechanisms
Maintenance mechanisms
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Glutamate
Glutamate
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Synaptic Plasticity
Synaptic Plasticity
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Calcium/Calmodulin-dependent Protein Kinase II (CaMKII)
Calcium/Calmodulin-dependent Protein Kinase II (CaMKII)
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Autophosphorylation
Autophosphorylation
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Synaptic Stability
Synaptic Stability
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CaMKII Role
CaMKII Role
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Hebb's Model
Hebb's Model
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LTP Steps
LTP Steps
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Induction in LTP
Induction in LTP
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Reciprocal Activation
Reciprocal Activation
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Liquid-liquid Phase Separation
Liquid-liquid Phase Separation
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Human Diseases and Synaptic Plasticity
Human Diseases and Synaptic Plasticity
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Calcium/Calmodulin-Dependent Protein Kinase II
Calcium/Calmodulin-Dependent Protein Kinase II
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Fluorescence Resonance Energy Transfer (FRET)
Fluorescence Resonance Energy Transfer (FRET)
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Dendritic Spines
Dendritic Spines
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Nitric Oxide in Synaptic Enhancement
Nitric Oxide in Synaptic Enhancement
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Cognitive Impairment from Stress
Cognitive Impairment from Stress
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Phosphorylation
Phosphorylation
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Calcium/calmodulin-dependent kinase II
Calcium/calmodulin-dependent kinase II
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Structural Basis of LTP
Structural Basis of LTP
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Structural LTP
Structural LTP
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Glutamate Receptors
Glutamate Receptors
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cGMP in LTP
cGMP in LTP
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Post-tetanic Potentiation
Post-tetanic Potentiation
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Study Notes
Molecular Mechanism of Hippocampal Long-Term Potentiation
- Long-term potentiation (LTP) is a cellular process thought to underlie learning and memory
- Postsynaptic NMDA receptor activation triggers AMPA receptor and protein trafficking to synapses
- Spine enlargement occurs alongside actin modulation (structural LTP or sLTP) during LTP
- Maintaining LTP despite protein turnover is a key research focus
- Ca²⁺ influx through NMDA receptors activates kinases like Ca²⁺/calmodulin-dependent protein kinase II (CaMKII)
- CaMKII can sustain long-term signaling via a reciprocally-activating complex with its substrate proteins, including Tiam1
- This regulation helps maintain downstream signalling
- CaMKII can condense at the synapse through liquid-liquid phase separation (LLPS)
- LLPS increases binding capacity at the synapse, supporting expanded protein complexes
- LLPS may function as a synapse tag to capture newly synthesized proteins
First Step of LTP: Induction
- LTP occurs in three phases: induction, expression, and maintenance
- Induction is triggered by tetanic stimulation, altering synapse function
- This leads to increased synaptic transmission (expression)
- Maintenance mechanisms sustain this enhanced transmission despite component turnover and reverse reactions
Debate on Pre- or Postsynaptic Expression and Maintenance of LTP
- Whether LTP is presynaptic (increased transmitter release) or postsynaptic (increased sensitivity to glutamate) was debated early
- Studies used radiolabeled glutamate, which suggested presynaptic enhancement
- Quantal analysis also supported presynaptic involvement
- Independent measures now show postsynaptic LTP expression, notably AMPA receptor changes
- Postsynaptic changes necessitate retrograde communication, possibly involving diffusible messengers (e.g., NO, CO, arachidonic acid)
AMPA Receptor Trafficking
- Advancements in technologies like neural gene introduction and fluorescence microscopy have aided LTP studies
- AMPA receptor translocation to the synapse is key to LTP expression and maintenance
- Lateral diffusion and exocytosis of AMPA receptors play roles in this translocation
Structural LTP
- LTP is linked to changes in dendritic spine structure (structural LTP, or sLTP)
- Tetanic stimulation triggers early spine enlargement, a process that can last several hours
- sLTP is linked to NMDA receptor activation
- Observations from in vivo studies, in addition to electrical recordings, demonstrated that spines undergo morphological changes
Trafficking of Various Proteins
- Many molecules, including receptors and signaling proteins, experience regulated trafficking during LTP
- This trafficking is crucial for maintaining synaptic function
Cellular Signaling Leading to LTP
- CaMKII is a key signaling molecule in LTP induction and maintenance
- Postsynaptic Ca²⁺ influx activates CaMKII
- Genetic ablation or inhibition of CaMKII impairs LTP and memory
- CaMKII can phosphorylate other proteins like AMPA receptors, enhancing synapse function
- The constitutive activity of CaMKII, even under basal conditions, is important for maintenance of LTP
Possible Substrates of CaMKII
- AMPA receptors, NMDA receptor subunits, Neuroligin, Shank, and other proteins are possible targets of CaMKII
- Phosphorylation of specific sites on certain proteins (e.g., AMPA receptor S831) may be vital for LTP expression
Liquid-Liquid Phase Separation of CaMKII
- CaMKII aggregation through liquid-liquid phase separation (LLPS) occurs within a synapse
- This LLPS process can result in the formation of synaptic nanodomains
- The temporary Ca²⁺ signal can be persistently remembered through LLPS condensates
- The formation of different protein phases within a synapse is important for LTP maintenance
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