DPR Exam III Short Answer Questions

• Describe Classical Conditioning

  • Sensory neuron action potential precedes shock for calmodulin to be activated, activating facilitated interneuron and serotonin release.
  • MAP K inhibits CREB 2 and activates CREB 1, directing gene transcription and PKA activation.
  • Action potential in sensory neuron causes more CA2+ to enter the cell, leading to Calmodulin activation and Adenyly cyclase 4 primed, enhancing AP and bigger PKA.
  • Calmodulin, associated with Adenylyl cyclase, enhances Action potential and bigger PKA activation.
• This kinase phosphorylates voltage-gated __________ ion channels, voltage-gated ________ ion channels, and the neurotransmitter release and vesicle recruitment machinery, enhancing the release of NT into the synapse

  This kinase phosphorylates voltage-gated** Ca2+ ** ion channels, voltage-gated K+ ion channels, and the neurotransmitter release and vesicle recruitment machinery enhancing the release of NT into the synapse
• What is the source of inhibitory signals in central axon regeneration, and how do we know?


  The source of inhibitory signals in central axon regeneration is the CNS myelin. We know this from past studies that were done with rats where if you block myelin sensory fibers extend normally and sprout new collaterals following denervation in myelin-free spinal cords. But if you don’t block the central axons of the branch are degenerated leaving a portion of the denervated, so little re- generation occurs in the myelin-rich cord.
• The other g protein-coupled receptor, the ____protein-coupled receptor activates ____ which converts ATP to ____ binds the inhibitory subunits and releases the catalytic subunits of the enzyme_____

  The other g protein-coupled receptor, the Gs protein-coupled receptor activates **adenyl cyclase ** which converts ATP to cAMP binds the inhibitory subunits, and releases the catalytic subunits of the enzyme PKA
• Describe Sensitization

  • Facilitated interneuron releases serotonin onto sensory neurons, binds to Gs and Gq/11 pathways, activates PKA & PKC, and increases NT release and EPSP.
  • PKC phosphorylates L-type ca2+ channels, increasing vesicle recruitment and docking average number of vesicles.
  • Broadened AP allows more CA2+ to enter the cell, enhancing vesicle recruitment.
  • Broadened Action Potential (AP) in Gs pathway due to PKA activation by cAMP from adenylyl cyclase.
• ____________ then translocate to the membrane where it first interacts with phosphatidyl serine and then _________ which removes the pseudosubstrate from the catalytic cavity

  PKA then translocate to the membrane where it first interacts with phosphatidyl serine and then ligands which removes the pseudosubstrate from the catalytic cavity
• This enzyme then diffuses through the membrane and interacts with its catalytic targets namely voltage-gated ________ channels and the neurotransmitter release and vesicle recruitment machinery

  This enzyme then diffuses through the membrane and interacts with its catalytic targets namely voltage-gated Ca2+ channels and the neurotransmitter release and vesicle recruitment machinery
• Identify the role of myelin in the regeneration of central neurons

  Myelin-forming oligodendrocytes have little or no ability to dispose of myelin, and the blood-brain barrier prevents the entry of macrophages, so the removal of debris depends on a limited quantity of resident macrophages and microglia.
• One is that postsynaptic injury causes axon terminals to lose their adhesiveness to synaptic sites so that they are subsequently wrapped by glia. The other is that glia initiates the process of synaptic stripping in response to factors released from the injured neuron or to changes in its cell surface.
• Describe the process of NMDA-dependent LTP. Be sure to include both short and long-term mechanisms mediating this phenomenon.

  Short-Term Mechanisms: High-frequency stimulation of presynaptic neurons initiates NMDA receptor-dependent LTP. Depolarization of the postsynaptic membrane releases Mg2+ block from NMDA receptors Ca2+ enters postsynaptic neurons, activating calcium/calmodulin-dependent protein kinase II (CaMKII). CaMKII phosphorylates AMPA receptors, increasing conductance and short-term synaptic response potentiation.
• Describe the process of NMDA-dependent LTP. Be sure to include both short and long-term mechanisms mediating this phenomenon.

  Long-Term Mechanisms:* The inflow of Ca2+ activates the Ras/MAPK pathway and CaMK kinase/CaMKIV pathway, activating transcription factors like CREB.* These transcription factors initiate the transcription of immediate early genes, leading to protein synthesis for long-term LTP maintenance.* New proteins regulate synaptic structure and function, creating a self-perpetuating cycle of gene expression and synaptic modifications.
• In a sentence describe how NMDA receptors are activated and what type of current results

  In LTP NMDA activation comes from depolarization in glutamate and a large influx of calcium renders LTP current
• Describe the prototypical process of NMDA-dependent LTP. Be sure to include short-term and long-term mechanisms mediating this phenomenon


  NMDA dependent LTP, NMDA receptor is glutamatergic and ionotropic, ion channel means it allows cations to flow through, allows Ca2+ to go through along with Na and K,also Mg is associated with pore as negative charge to block the pore, Mg needs additional force to be ejected
• Briefly explain the difference between E-LTP and L-LTP. What are the cellular events that differentiate them

  Early long-term potentiation (E-LTP) is the first step of long-term potentiation (LTP). We can study the form of synaptic plasticity, and it is responsible for the increase in synaptic strength.L- Long-term potentiation (LTP) is known for continuous increase in the strength of synapses by stimulating the high-frequency of chemical synapses. We can study the LTP By carrying out the hippocampus,
• Cellular changes are :LTP originates when we stimulate a single synapse repeatedly.This event results in stimulation that causes a calcium- and CaMKII-dependent cellular cascade, which results in the insertion of more AMPA receptors which are present in synapses
• Describe the prototypical process of NMDA-dependent LTP. Be sure to include short-term and long-term mechanisms mediating this phenomenon

  NMDA-dependent LTP, NMDA receptor is glutamatergic and ionotropic, ion channel means it allows cations to flow through, allows Ca2+ to go through along with Na and K,also, Mg is associated with pores as negative charge to block the pore, Mg needs additional force to be ejected
• What is the source of inhibitory signals in central axon regeneration, and how do we know?

  • Myelin-Associated Inhibitors:
  • In vitro experiments show limited axon outgrowth in cultured neurons plated on myelin or myelin-derived proteins.
  • Antibodies or receptor blockers against these inhibitors promoted axon regeneration in animal models of spinal cord injury or optic nerve crush.
  • Specific inhibitors like Nogo, myelin-associated glycoprotein (MAG), and oligodendrocyte-myelin glycoprotein (OMgp) were identified.
• Extracellular Matrix Components in the Glial Scar:

  The glial scar contains reactive astrocytes, microglia, and a dense extracellular matrix rich in chondroitin sulfate proteoglycans (CSPGs).

  CSPGs, produced by reactive astrocytes, inhibit axon growth and regeneration.

  Treatment with chondroitinase ABC or blocking specific CSPG receptors on neurons enhanced axon regeneration
• Mossy Fiber LTP:* Located at synapses between mossy fibers and CA3 pyramidal neurons.* Primarily presynaptic, involving increased neurotransmitter release.* NMDA receptor-independent, relying on presynaptic kainate receptors and cAMP signaling pathways.
• Schaffer collateral LTP:


  * Located at synapses between Schaffer collaterals and CA1 pyramidal neurons.* Primarily postsynaptic, involving activation of NMDA receptors and synaptic strength increase.* NMDA receptor-dependent, requiring large postsynaptic calcium influx.
• Direct perforant path LTP:

  * Located at synapses between perforant path and dentate gyrus granule cells.* Shares similarities with both types, exhibiting both presynaptic and postsynaptic components.
• Describe the three types of LTP discussed in the hippocampus. What are they? What are the similarities and what are the differences?

  Differences:* Mossy fiber LTP is primarily presynaptic and NMDA receptor-independent.* Schaffer collateral LTP is postsynaptic and NMDA receptor-dependent.* Direct perforant path LTP combines presynaptic and postsynaptic components.
• Describe the three types of LTP discussed in the hippocampus. What are they? What are the similarities and what are the differences?

  Similarities:* All three LTPs involve long-lasting synaptic strength increases and contribute to hippocampal plasticity and memory formation.* Share common signaling pathways, including calcium involvement and kinase activation.
• Behavioral sensitization, mediated by synaptic facilitation of the gill withdrawal reflex in Aplysia is mediation by connections between the ________ interneuron from the tail and the sensory neurons innervating the terminal of the ________ and the mantle.

  Behavioral sensitization, mediated by synaptic facilitation of the gill withdrawal reflex in Aplysia is mediation by connections between the facilitated interneuron from the tail and the sensory neurons innervating the terminal of the siphon and the mantle.
• Describe the presynaptic mechanism that underlies mossy fiber LTP

  Mossy fiber long-term potentiation (LTP) is a form of synaptic plasticity that occurs at the synapses between mossy fibers, which are the axons of dentate granule cells, and the proximal dendrites of CA3 pyramidal neurons in the hippocampus. The presynaptic mechanism underlying mossy fiber LTP involves an increase in the probability of neurotransmitter release from the presynaptic terminals of mossy fibers.
• Additionally, the induction of mossy fiber LTP is also associated with structural changes in the presynaptic terminals, including an increase in the number of docked vesicles and an expansion of the active zone area, further contributing to the enhanced probability of neurotransmitter release.
• Mossy Fiber Long-Term Potentiation (LTP) Overview

  • LTP is a synaptic plasticity at synapses between mossy fibers and CA3 pyramidal neurons.
  • This increase is triggered by presynaptic calcium levels, activated by high-frequency stimulation.
  • Elevated calcium levels activate signaling pathways, including CaMKII and MAPK pathways.
  • These pathways phosphorylate and modulate presynaptic proteins involved in neurotransmitter release
  • Structural changes in presynaptic terminals increase the number of docked vesicles enhancing neurotransmitter release probability.
• In contrast, classical conditioning is an associative form of learning where a neutral stimulus (conditioned stimulus, CS) is paired with a biologically significant stimulus (unconditioned stimulus, US), resulting in the CS eliciting a response (conditioned response, CR) similar to the one initially evoked by the US alone. The experimental paradigm for classical conditioning involves repeatedly pairing the CS (e.g., a tone) with the US (e.g., a puff of air to the eye, causing an eye blink response) until the CS alone can elicit the CR (eye blink).
• Sensitization is a non-associative form of learning where repeated exposure to a single, intense stimulus leads to an enhanced behavioral response to that stimulus or a similar stimulus. The experimental paradigm for sensitization typically involves the application of a strong, often noxious, stimulus, such as a tail shock or a bright light, and measuring the subsequent amplification of a specific behavioral response, such as gill withdrawal in Aplysia or an enhanced startle reflex in mammals.

   
• Molecularly, sensitization is often associated with the modulation of existing proteins and signaling pathways, such as the activation of protein kinases (e.g., PKA, PKC) and the regulation of ion channels and synaptic vesicle release machinery. Classical conditioning, on the other hand, involves more complex molecular changes, including gene expression alterations, protein synthesis, and structural remodeling of synapses.
• Short-Term Mechanisms:

  • High-frequency stimulation of presynaptic neurons initiates NMDA receptor-dependent LTP.
  • Depolarization of the postsynaptic membrane releases Mg2+ block from NMDA receptors
  • Ca2+ enters postsynaptic neurons, activating calcium/calmodulin-dependent protein kinase II (CaMKII).
  • CaMKII phosphorylates AMPA receptors, increasing conductance and short-term synaptic response potentiation.
• Long-Term Mechanisms:

  The inflow of Ca2+ activates the Ras/MAPK pathway and CaMK kinase/CaMKIV pathway, activating transcription factors like CREB.

  These transcription factors initiate the transcription of immediate early genes, leading to protein synthesis for long-term LTP maintenance.

  New proteins regulate synaptic structure and function, creating a self-perpetuating cycle of gene expression and synaptic modifications.

  These changes at the synapse underlie long-term maintenance of NMDA receptor-dependent LTP, a cellular mechanism for learning and memory formation.
• E-LTP:

  E-LTP is the initial, transient phase of LTP that lasts for about 1-3 hours.

  It is primarily mediated by post-translational modifications of existing proteins, such as the phosphorylation of AMPA receptors by kinases like CaMKII.

  This increase in AMPA receptor conductance leads to a short-term enhancement of synaptic strength.

  E-LTP does not require new protein synthesis and is independent of gene transcription.
• L-LTP:

  • It requires new gene expression and de novo protein synthesis.
  • The influx of calcium during LTP induction activates signaling cascades that lead to the activation of transcription factors like CREB, initiating the transcription of specific genes.
  • The newly synthesized proteins are involved in structural remodeling of the synapse, such as the growth of new dendritic spines, the trafficking and insertion of AMPA receptors, and the reorganization of the actin cytoskeleton.
• Identify the role of myelin in the regeneration of central neurons

  Myelin, produced by oligodendrocytes in the central nervous system, plays a crucial role in the regeneration of central neurons. Recent studies have shown that modulating these inhibitory signals or targeting specific signaling pathways can promote axonal regeneration and functional recovery. Remyelination by oligodendrocytes not only restores conduction velocity but also provides trophic support for regenerating axons.
• Role of Myelin and Nerve Sheaths in Peripheral Nerve Regeneration

  • Schwann cells proliferate and migrate to the injury site, secreting enzymes to degrade myelin debris, and facilitating axon regeneration.
  • Schwann cells remyelinate new axons as regenerating axons grow, restoring saltatory conduction and nerve function.
  • Schwann cells and nerve sheath cells produce and remodel the extracellular matrix, providing a supportive environment for axon regeneration
• What is the source of inhibitory signals in central axon regeneration, and how do we know?

  • Myelin-associated inhibitors and extracellular matrix components limit central axon regeneration post-injury.
  • Glial scar, containing astrocytes, microglia, and a dense extracellular matrix, enhances axon regeneration.
  • Genetic manipulation of signaling pathways mediates inhibitory effects of myelin-associated inhibitors and CSPGs.
  • Neutralizing or blocking these inhibitors with antibodies or receptor blockers promotes axon regeneration.
  • Specific inhibitors like Nogo, MAG, and OMgp inhibit axon growth.
• Briefly describe Hebb’s rule.

  It states that when a presynaptic neuron repeatedly participates in firing a postsynaptic neuron, the strength of the synaptic connection between them increases. This is often summarized as "neurons that fire together, wire together."
• In a sentence describe how NMDA receptors are activated and what type of current results.

  
  

  NMDA receptors are activated by the simultaneous binding of glutamate and the removal of magnesium block by depolarization of the postsynaptic membrane. This results in the influx of calcium ions, producing an excitatory current.
• What is the source of inhibitory signals in central axon regeneration, and how do we know?

  The primary sources of inhibitory signals in central axon regeneration are myelin-associated inhibitors (e.g., Nogo, MAG, OMgp) and components of the extracellular matrix in the glial scar, particularly chondroitin sulfate proteoglycans (CSPGs). This knowledge has been gained through in vitro experiments, identification of specific inhibitors, and studies involving neutralization or blocking of these inhibitors, which promoted axon regeneration in animal models of CNS injury.