Podcast
Questions and Answers
What is the first step in the life cycle of neurotransmission?
What is the first step in the life cycle of neurotransmission?
- Transmitter Inactivation
- Storage
- Synthesis (correct)
- Receptor Binding
Which ionotropic receptor is associated with serotonin neurotransmission?
Which ionotropic receptor is associated with serotonin neurotransmission?
- AMPA Receptor
- 5-HT3 Receptor (correct)
- nACh receptor
- GABAA Receptor
Which of the following ionotropic receptors is primarily involved in mediating excitatory synaptic transmission?
Which of the following ionotropic receptors is primarily involved in mediating excitatory synaptic transmission?
- GABAA Receptor
- AMPA/Kainate Receptors (correct)
- Purines Receptors
- Glycine Receptor
Which step in the life cycle of neurotransmission occurs after neurotransmitter release?
Which step in the life cycle of neurotransmission occurs after neurotransmitter release?
What type of receptors do NMDA belong to?
What type of receptors do NMDA belong to?
What type of receptor are NMDA and AMPA classified as?
What type of receptor are NMDA and AMPA classified as?
Which compound is noted as a pore-blocker of NMDA receptors?
Which compound is noted as a pore-blocker of NMDA receptors?
What is the primary neurotransmitter associated with NMDA receptors in the context of schizophrenia?
What is the primary neurotransmitter associated with NMDA receptors in the context of schizophrenia?
How many NMDARs are typically found in a postsynaptic density (PSD) of around 350nm?
How many NMDARs are typically found in a postsynaptic density (PSD) of around 350nm?
In terms of receptor localization, where are NMDA receptors primarily located within the postsynaptic density?
In terms of receptor localization, where are NMDA receptors primarily located within the postsynaptic density?
Which ionotropic receptor family is involved with psychopharmacological effects linked to drugs like ketamine?
Which ionotropic receptor family is involved with psychopharmacological effects linked to drugs like ketamine?
What is the estimated number of AMPARs typically found in a PSD compared to NMDARs?
What is the estimated number of AMPARs typically found in a PSD compared to NMDARs?
Which of the following is NOT a stated NMDA receptor pore-blocker?
Which of the following is NOT a stated NMDA receptor pore-blocker?
What effect does the RNA editing of GluA2 have on its properties?
What effect does the RNA editing of GluA2 have on its properties?
What happens when the editing site complementary sequence (ECS) is deleted in GluA2?
What happens when the editing site complementary sequence (ECS) is deleted in GluA2?
Extended exposure to glutamate affects AMPA receptors by causing what change?
Extended exposure to glutamate affects AMPA receptors by causing what change?
What would be the consequence of an increase in unedited GluA2 mRNA?
What would be the consequence of an increase in unedited GluA2 mRNA?
The strong electrostatic repulsion by which amino acid is responsible for the low permeability of AMPA receptor-channels with edited GluA2?
The strong electrostatic repulsion by which amino acid is responsible for the low permeability of AMPA receptor-channels with edited GluA2?
What is the outcome in wild-type littermates that possess the normal Q/R editing site compared to those with impaired editing?
What is the outcome in wild-type littermates that possess the normal Q/R editing site compared to those with impaired editing?
What is one significant consequence of channel closure in AMPA receptors after glutamate exposure?
What is one significant consequence of channel closure in AMPA receptors after glutamate exposure?
Which modification in AMPA receptor composition leads to changes in its calcium permeability?
Which modification in AMPA receptor composition leads to changes in its calcium permeability?
What is one of the key factors influencing the magnitude of the postsynaptic response?
What is one of the key factors influencing the magnitude of the postsynaptic response?
What is the primary characteristic of ionotropic receptors in terms of synaptic action duration?
What is the primary characteristic of ionotropic receptors in terms of synaptic action duration?
How many subunits do ionotropic receptors typically have?
How many subunits do ionotropic receptors typically have?
Which of these receptors is NOT classified as an ionotropic receptor?
Which of these receptors is NOT classified as an ionotropic receptor?
What structural feature is typical of each subunit in ionotropic receptors?
What structural feature is typical of each subunit in ionotropic receptors?
What aspect affects the postsynaptic receptor's response alongside receptor number and neurotransmitter amount?
What aspect affects the postsynaptic receptor's response alongside receptor number and neurotransmitter amount?
Which ionotropic receptor is specifically known for mediating fast excitatory transmission in the central nervous system?
Which ionotropic receptor is specifically known for mediating fast excitatory transmission in the central nervous system?
What is the general implication of neurotransmitter release amount on postsynaptic receptors?
What is the general implication of neurotransmitter release amount on postsynaptic receptors?
Where are mGluRs primarily located?
Where are mGluRs primarily located?
What is the role of PSD-95 in relation to AMPARs?
What is the role of PSD-95 in relation to AMPARs?
What is the function of TARPs like Stargazin?
What is the function of TARPs like Stargazin?
How does increasing Stargazin expression affect AMPARs?
How does increasing Stargazin expression affect AMPARs?
What happens to the functional AMPARs in the cerebellum of stg mice?
What happens to the functional AMPARs in the cerebellum of stg mice?
What is the effect of increased PSD-95 expression on AMPARs?
What is the effect of increased PSD-95 expression on AMPARs?
What is the role of Stargazin's PDZ domain?
What is the role of Stargazin's PDZ domain?
Which receptors are primarily affected by TARPs?
Which receptors are primarily affected by TARPs?
What was observed with exogenous glutamate application in controlled levels of Stargazin?
What was observed with exogenous glutamate application in controlled levels of Stargazin?
Flashcards are hidden until you start studying
Study Notes
NMDA Receptors, Hallucinations and Schizophrenia
- HaInogenic compounds like PCP, Ketamine, and MK-801 block NMDA receptors, disrupting synaptic transmission and causing altered perceptions and cognitive dysfunction.ons, often associated with various psychiatric conditions.
- The glutamate hypothesis of schizophrenia proposes that dysregulation of glutamate, particularly at the NMDA receptor level, plays a critical role in the pathophysiology of schizophrenia. This hypothesis is supported by observations that decreased NMDA receptor function may lead to symptoms such as hallucinations, impaired cognition, and negative symptoms, indicating a complex interplay between neurotransmitter systems in mental health disorders.
NMDA Receptors and Glutamate Excitotoxicity
- Glutamate excitotoxicity is an overstimulation of neurons by glutamate.
- This occurs when glutamate binds to NMDA receptors.
Lecture Outline
- Glutamatergic ionotropic receptors include AMPA, Kainate, and NMDA receptors.
Distribution of Ionotropic Glutamate Receptors: Postsynaptic Density (PSD)
- The postsynaptic density (PSD) contains a variety of proteins including ionotropic receptors.
- NMDA receptors are located in the center of the PSD, while AMPA receptors are more peripherally located.
- A typical PSD is approximately 350nm long and contains about 20 NMDA receptors and 10-50 AMPA receptors.
The Life Cycle of Neurotransmission
- The life cycle of neurotransmission consists of several steps:
- synthesis
- storage
- release
- receptor binding
- inactivation
Ionotropic and Metabotropic Receptors
- Ionotropic receptors are fast acting, with effects occurring over milliseconds, while metabotropic receptors are slower, with effects persisting for seconds to minutes.
Ionotropic Receptor Families
- Ionotropic receptors are composed of 3 to 5 subunits.
- Each subunit has a membrane domain with four membrane-spanning alpha helices (M1-M4) and a short extracellular C-terminus.
AMPA Receptors: Subunit Composition
- AMPA receptors can have various subunit compositions.
- The GluA2 subunit exhibits low calcium permeability due to a strong electrostatic repulsion by an arginine.
- RNA editing switches a single amino acid in GluA2 reducing calcium permeability.
- Deletion of the editing site complementary sequence (ECS) in the intron impairs GluA2 Q/R RNA editing.
- Deletion of the ECS leads to approximately 25% unedited GluA2 mRNA at the Q/R site compared to wild-type littermates.
AMPA Receptors: Desensitization
- Prolonged exposure to glutamate can lead to a change in the dimer bond at the ligand binding domain, resulting in channel closure.
- mGluRs are located on the periphery of the PSD.
AMPA Receptor Trafficking
- The PSD-95 protein binds to NMDA receptors, AMPA receptors, and other proteins, concentrating these receptors at the synapse.
- Transmembrane AMPA receptor regulatory proteins (TARPs) regulate the trafficking, synaptic localization, and gating of AMPA receptors.
- AMPAR trafficking is complex and tightly controlled.
- TARP composition differs across the brain.
TARPs: Stargazin
- Stg mice lack Stargazin, leading to a deficiency in functional AMPARs in the cerebellum.
- Increasing Stargazin expression increases the presence of AMPARs in the membrane, but does not alter evoked responses.
- Stargazin guides AMPARs to the membrane and anchors them to the synapse via its PDZ domain.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
