Chemistry and Physiology of the Synapse

Question 1

Two families of postsynaptic receptors

Answer 1

Question 2

Ionotropic receptors

• ,,, gated ion channels - responsible for fast transmission of information to the postsynaptic neuron
• Similar to the … gated Na+ and K+ channels that control the action potential but opened by … binding rather than … changes
• … = NT
• It binds to the channel, changes it’s …, thus opening it and allowing ions to flux through central pore
• Channels made of 4 or 5 subunits that fold together to form the central pore

Answer 2

• Ligand gated ion channels - responsible for fast transmission of information to the postsynaptic neuron
• Similar to the voltage gated Na+ and K+ channels that control the action potential but opened by ligand binding rather than voltage changes
• Ligand = NT
• It binds to the channel, changes it’s conformation, thus opening it and allowing ions to flux through central pore
• Channels made of 4 or 5 subunits that fold together to form the central pore

Question 3

Ionotropic receptors

• Ligand gated ion channels - responsible for … transmission of information to the postsynaptic neuron
• Similar to the voltage gated Na+ and K+ channels that control the action potential but opened by ligand binding rather than voltage changes
• Ligand = NT
• It binds to the channel, changes it’s …, thus opening it and allowing ions to flux through … pore
• Channels made of 4 or 5 subunits that fold together to form the … pore

Answer 3

• Ligand gated ion channels - responsible for fast transmission of information to the postsynaptic neuron
• Similar to the voltage gated Na+ and K+ channels that control the action potential but opened by ligand binding rather than voltage changes
• Ligand = NT
• It binds to the channel, changes it’s conformation, thus opening it and allowing ions to flux through central pore
• Channels made of 4 or 5 subunits that fold together to form the central pore

Question 4

• Ionotropic Receptors = … transmission
• Crucial for Synaptic integration
• Example … Receptors (NMDA, non NMDA)

Answer 4

• Ionotropic Receptors = fast transmission
• Crucial for Synaptic integration
• Example Glu Receptors (NMDA, non NMDA)

Question 5

• … Receptors =
• Shortcut pathway
• … messenger cascades

Answer 5

• Metabotropic Receptors =
• Shortcut pathway
• Second messenger cascades

Question 6

Receptor variation

• Pharmacology - what transmitter binds to the receptor and how drugs interact with them
  
  • … - A drug that can combine with a receptor on a cell to produce a physiological reaction
  • … - A drug that blocks the activity of the agonist or endogenous ligand (NT)
• … - Rate of transmitter binding and channel gating determine the duration of their effects
• Selectivity - What ions are fluxed (Na+, Cl-, K+ and/or Ca2+)
• … - The rate of flux helps determine effect magnitude

Answer 6

• Pharmacology - what transmitter binds to the receptor and how drugs interact with them
  
  • Agonist - A drug that can combine with a receptor on a cell to produce a physiological reaction
  • Antagonist - A drug that blocks the activity of the agonist or endogenous ligand (NT)
• Kinetics - Rate of transmitter binding and channel gating determine the duration of their effects
• Selectivity - What ions are fluxed (Na+, Cl-, K+ and/or Ca2+)
• Conductance - The rate of flux helps determine effect magnitude

Question 7

… - A drug that can combine with a receptor on a cell to produce a physiological reaction

Answer 7

Agonist - A drug that can combine with a receptor on a cell to produce a physiological reaction

Question 8

… - A drug that blocks the activity of the agonist or endogenous ligand (NT)

Answer 8

Antagonist - A drug that blocks the activity of the agonist or endogenous ligand (NT)

Question 9

Fast Synaptic transmission (1)

• …. ionotropic receptors in general flux Na+, which causes an EPSP (Excitatory Post Synaptic Potential) depolarizing the postsynaptic neuron. Enough depolarization, due to multiple receptors being activated or repeated activation, can cause the postsynaptic cell to fire an action potential.
• …. ionotropic receptors flux Cl-, which causes an IPSP (Inhibitory Post Synaptic Potential) hyperpolarizing the postsynaptic neuron. This inhibits the neuron from firing unless there is sufficient glutamate stimulation to counteract the hyperpolarization.

Answer 9

• Glutamate ionotropic receptors in general flux Na+, which causes an EPSP (Excitatory Post Synaptic Potential) depolarizing the postsynaptic neuron. Enough depolarization, due to multiple receptors being activated or repeated activation, can cause the postsynaptic cell to fire an action potential.
• GABA ionotropic receptors flux Cl-, which causes an IPSP (Inhibitory Post Synaptic Potential) hyperpolarizing the postsynaptic neuron. This inhibits the neuron from firing unless there is sufficient glutamate stimulation to counteract the hyperpolarization.

Question 10

Fast Synaptic transmission (1)

• Glutamate ionotropic receptors in general flux …+, which causes an …PSP (… Post Synaptic Potential) depolarizing the postsynaptic neuron. Enough depolarization, due to multiple receptors being activated or repeated activation, can cause the postsynaptic cell to fire an action potential.
• GABA ionotropic receptors flux …-, which causes an …PSP (… Post Synaptic Potential) hyperpolarizing the postsynaptic neuron. This … the neuron from firing unless there is sufficient glutamate stimulation to counteract the hyperpolarization.

Answer 10

• Glutamate ionotropic receptors in general flux Na+, which causes an EPSP (Excitatory Post Synaptic Potential) depolarizing the postsynaptic neuron. Enough depolarization, due to multiple receptors being activated or repeated activation, can cause the postsynaptic cell to fire an action potential.
• GABA ionotropic receptors flux Cl-, which causes an IPSP (Inhibitory Post Synaptic Potential) hyperpolarizing the postsynaptic neuron. This inhibits the neuron from firing unless there is sufficient glutamate stimulation to counteract the hyperpolarization.

Question 11

Acetylcholine, serotonin and ATP also active … receptors

Answer 11

Acetylcholine, serotonin and ATP also active ionotropic receptors

Question 12

Fast Synaptic Transmission (2)

• Acetylcholine, serotonin and ATP also active … receptors
• … receptors at the neuromuscular junction are the most well studied … receptors. Their activation by acetylcholine causes the excitation and contraction of muscle cells.
• An integration of all the changes in membrane potential will decide whether a postsynaptic neuron will fire an … … or not.

Answer 12

• Acetylcholine, serotonin and ATP also active ionotropic receptors
• Nicotinic receptors at the neuromuscular junction are the most well studied ionotropic receptors. Their activation by acetylcholine causes the excitation and contraction of muscle cells.
• An integration of all the changes in membrane potential will decide whether a postsynaptic neuron will fire an action potential or not.

Question 13

Synaptic integration on postsynaptic neurons

• … - Glutamate receptors - glutamate molecules released in synaptic cleft and bind to these - channels open - sodium ions through - more positive - increase in post synaptic membrane potential - …PSP lasts for a few milliseconds
  
  • … - GABA molecules - activation of GABA specific receptors - chloride ions through - membrane potential more negative - ..PSP

Answer 13

• Excitatory - Glutamate receptors - glutamate molecules released in synaptic cleft and bind to these - channels open - sodium ions through - more positive - increase in post synaptic membrane potential - EPSP lasts for a few milliseconds
• Inhibitory - GABA molecules - activation of GABA specific receptors - chloride ions through - membrane potential more negative - IPSP

Question 14

Synaptic integration on postsynaptic neurons

• Excitatory - … receptors - … molecules released in synaptic cleft and bind to these - channels open - sodium ions through - more positive - increase in post synaptic membrane potential - EPSP lasts for a few milliseconds
• Inhibitory - … molecules - activation of … specific receptors - chloride ions through - membrane potential more negative - IPSP

Answer 14

• Excitatory - Glutamate receptors - glutamate molecules released in synaptic cleft and bind to these - channels open - sodium ions through - more positive - increase in post synaptic membrane potential - EPSP lasts for a few milliseconds
• Inhibitory - GABA molecules - activation of GABA specific receptors - chloride ions through - membrane potential more negative - IPSP

Question 15

Based on their pharmacology, three types of ionotropic receptor have been described that respond to glutamate.

• N…
• A…
• K…

Answer 15

• NMDA
• AMPA
• Kainate
  
  • ​Names based on the agonists selective for them

Question 16

Pharmacology of ionotropic GluRs

• 1) NMDA receptors
  
  • Agonist NMDA (N-methyl D-aspartate)
  • Antagonist APV (2-amino-5-phosphonovaleric acid)
• 2) … receptors
  
  • Agonist … (a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid)
  • Antagonist CNQX (6-cyano-7-nitroquinoxaline-2,3-dione)
• 3) … receptors
  
  • Agonist … acid
  • Antagonist CNQX (6-cyano-7-nitroquinoxaline-2,3-dione)

Answer 16

• 1) NMDA receptors
  
  • Agonist NMDA (N-methyl D-aspartate)
  • Antagonist APV (2-amino-5-phosphonovaleric acid)
• 2) AMPA receptors
  
  • Agonist AMPA (a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid)
  • Antagonist CNQX (6-cyano-7-nitroquinoxaline-2,3-dione)
• 3) Kainate receptors
  
  • Agonist Kainic acid
  • Antagonist CNQX (6-cyano-7-nitroquinoxaline-2,3-dione)

Question 17

Pharmacology of ionotropic GluRs

• 1) … receptors
  
  • Agonist … (N-methyl D-aspartate)
  • Antagonist APV (2-amino-5-phosphonovaleric acid)
• 2) AMPA receptors
  
  • Agonist AMPA (a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid)
  • Antagonist CNQX (6-cyano-7-nitroquinoxaline-2,3-dione)
• 3) Kainate receptors
  
  • Agonist Kainic acid
  • Antagonist CNQX (6-cyano-7-nitroquinoxaline-2,3-dione)

Answer 17

• 1) NMDA receptors
  
  • Agonist NMDA (N-methyl D-aspartate)
  • Antagonist APV (2-amino-5-phosphonovaleric acid)
• 2) AMPA receptors
  
  • Agonist AMPA (a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid)
  • Antagonist CNQX (6-cyano-7-nitroquinoxaline-2,3-dione)
• 3) Kainate receptors
  
  • Agonist Kainic acid
  • Antagonist CNQX (6-cyano-7-nitroquinoxaline-2,3-dione)

Question 18

Selectivity and conductance of GluRs

• Non-NMDA receptors (… and …)
  
  • Fast opening channels permeable to Na+ and K+
  • Responsible for … phase EPSP
• NMDA receptor
• Slow opening channel - permeable to Ca2+ as well and Na+ and K+
• BUT ALSO
  
  • Requires an extracellular … as a cofactor to open the channel
  • Gated by membrane voltage - Mg2+ ion plugs pore at resting membrane potentials. When membrane depolarizes Mg2+ ejected from channel by electrostatic repulsion allowing conductance of the other cations, activity-dependant synaptic modification
  • NMDA receptors responsible for a … phase EPSP
  • Activated only in an already depolarized membrane in the presence of glutamate
• EPSP - can have early phase and late phase

Answer 18

• Non-NMDA receptors (AMPA and Kainate)
  
  • Fast opening channels permeable to Na+ and K+
  • Responsible for early phase EPSP
• NMDA receptor
  
  • Slow opening channel - permeable to Ca2+ as well and Na+ and K+
• BUT ALSO
  
  • Requires an extracellular glycine as a cofactor to open the channel
  • Gated by membrane voltage - Mg2+ ion plugs pore at resting membrane potentials. When membrane depolarizes Mg2+ ejected from channel by electrostatic repulsion allowing conductance of the other cations, activity-dependant synaptic modification
  • NMDA receptors responsible for a late phase EPSP
  • Activated only in an already depolarized membrane in the presence of glutamate
• EPSP - can have early phase and late phase

Question 19

Selectivity and conductance of GluRs

• Non-NMDA receptors (AMPA and Kainate)
  
  • Fast opening channels permeable to …+ and …+
  • Responsible for early phase EPSP
• NMDA receptor
  
  • Slow opening channel - permeable to …+ as well and …+ and …+
• BUT ALSO
  
  • Requires an extracellular glycine as a cofactor to open the channel
  • Gated by membrane voltage - Mg2+ ion plugs pore at resting membrane potentials. When membrane depolarizes Mg2+ ejected from channel by electrostatic repulsion allowing conductance of the other cations, …-dependant synaptic ….
  • NMDA receptors responsible for a late phase EPSP
  • Activated only in an already depolarized membrane in the presence of …
• EPSP - can have early phase and late phase

Answer 19

• Non-NMDA receptors (AMPA and Kainate)
  
  • Fast opening channels permeable to Na+ and K+
  • Responsible for early phase EPSP
• NMDA receptor
  
  • Slow opening channel - permeable to Ca2+ as well and Na+ and K+
• BUT ALSO
  
  • Requires an extracellular glycine as a cofactor to open the channel
  • Gated by membrane voltage - Mg2+ ion plugs pore at resting membrane potentials. When membrane depolarizes Mg2+ ejected from channel by electrostatic repulsion allowing conductance of the other cations, activity-dependant synaptic modification
  • NMDA receptors responsible for a late phase EPSP
  • Activated only in an already depolarized membrane in the presence of glutamate
• EPSP - can have early phase and late phase

Question 20

NMDA receptors - regulation of channel opening

• …PSPs measured from resting potential higher than Mg2+ blockade. In presence or absence of AMPA or NMDA antagonists. Slower kinetics of NMDA channel -… phase EPSP
• Influx of Ca2+ as well as Na+ leads to activation of a number of enzymes and other cellular events that cause widespread changes in the postsynaptic cell (neuroplasticity). This action of NMDA receptors and the resultant neuroplasticity may be the molecular mechanisms that leads to … term memory formation.

Answer 20

• EPSPs measured from resting potential higher than Mg2+ blockade. In presence or absence of AMPA or NMDA antagonists. Slower kinetics of NMDA channel -late phase EPSP
• Influx of Ca2+ as well as Na+ leads to activation of a number of enzymes and other cellular events that cause widespread changes in the postsynaptic cell (neuroplasticity). This action of NMDA receptors and the resultant neuroplasticity may be the molecular mechanisms that leads to long term memory formation.

Question 21

NMDA receptors - dysregulation

• NMDA receptors and …?
  
  • NMDA receptors also inhibited by phencyclidine (PCP, angel dust) and MK801; both bind in the open pore.
  • Blockade of NMDA receptors in this way produces symptoms that resemble the hallucinations associated with S…
  • Certain … drugs enhance current flow through NMDA channels
• …. excitotoxicity
  
  • Excessive Ca2+ influx into the cell, which activates calcium-dependent enzymes that degrade proteins, lipids and nucleic acids
  • This kind of cell damage occurs after cardiac arrest, stroke, oxygen deficiency, and repeated intense … (status epilepticus)

Answer 21

• NMDA receptors and Schizophrenia?
  
  • NMDA receptors also inhibited by phencyclidine (PCP, angel dust) and MK801; both bind in the open pore.
  • Blockade of NMDA receptors in this way produces symptoms that resemble the hallucinations associated with Schizophrenia
  • Certain antipsychotic drugs enhance current flow through NMDA channels
• Glutamate excitotoxicity
  
  • Excessive Ca2+ influx into the cell, which activates calcium-dependent enzymes that degrade proteins, lipids and nucleic acids
  • This kind of cell damage occurs after cardiac arrest, stroke, oxygen deficiency, and repeated intense seizures (status epilepticus)

Question 22

NMDA receptors - dysregulation

• NMDA receptors and Schizophrenia?
  
  • NMDA receptors also inhibited by … (PCP, angel dust) and MK801; both bind in the open pore.
  • Blockade of NMDA receptors in this way produces symptoms that resemble the hallucinations associated with Schizophrenia
  • Certain antipsychotic drugs enhance current flow through NMDA channels
• Glutamate …
  
  • Excessive Ca2+ influx into the cell, which activates calcium-dependent enzymes that degrade proteins, lipids and nucleic acids
  • This kind of cell damage occurs after cardiac arrest, stroke, oxygen deficiency, and repeated intense seizures (status epilepticus)

Answer 22

• NMDA receptors and Schizophrenia?
  
  • NMDA receptors also inhibited by phencyclidine (PCP, angel dust) and MK801; both bind in the open pore.
  • Blockade of NMDA receptors in this way produces symptoms that resemble the hallucinations associated with Schizophrenia
  • Certain antipsychotic drugs enhance current flow through NMDA channels
• Glutamate excitotoxicity
  
  • Excessive Ca2+ influx into the cell, which activates calcium-dependent enzymes that degrade proteins, lipids and nucleic acids
  • This kind of cell damage occurs after cardiac arrest, stroke, oxygen deficiency, and repeated intense seizures (status epilepticus)

Question 23

Other ionotropic receptors (Ligand-gated ion channels)

• Glutamate - …
• GABA A - … - brain
• Glycine - … (spinal cord and brain stem)
• Nicotine - excitatory at NMJ , excitatory or modulatory in the CNS
• Serotonin - … or modulatory
• ATP - …

Answer 23

• Glutamate - excitatory
• GABA A - inhibitory - brain
• Glycine - inhibitory (spinal cord and brain stem)
• Nicotine - excitatory at NMJ , excitatory or modulatory in the CNS
• Serotonin - excitatory or modulatory
• ATP - excitatory

Question 24

Other ionotropic receptors (Ligand-gated ion channels)

• Glutamate - excitatory
• GABA A - … - brain
• Glycine - inhibitory (spinal cord and brain stem)
• Nicotine - … at NMJ , … or … in the CNS
• Serotonin - excitatory or …
• ATP - excitatory

Answer 24

• Glutamate - excitatory
• GABA A - inhibitory - brain
• Glycine - inhibitory (spinal cord and brain stem)
• Nicotine - excitatory at NMJ , excitatory or modulatory in the CNS
• Serotonin - excitatory or modulatory
• ATP - excitatory

Question 25

Metabotropic receptors

• Transduce signals into the cell not directly through an ion channel but through activation of a G-protein which in turn triggers a series of … events (that can lead to ion channel …)
• G-protein coupled receptors (GPCRs) - seven transmembrane domain protein
  
  • multiple receptors have been described for every known neurotransmitter
  • transmitter binds to … domain of receptor
  • binding triggers … of a heteromeric G-protein on the intracellular surface transduces signal across the cell membrane

Answer 25

• Transduce signals into the cell not directly through an ion channel but through activation of a G-protein which in turn triggers a series of intracellular events (that can lead to ion channel opening)
• G-protein coupled receptors (GPCRs) - seven transmembrane domain protein
  
  • multiple receptors have been described for every known neurotransmitter
  • transmitter binds to extracellular domain of receptor
  • binding triggers uncoupling of a heteromeric G-protein on the intracellular surface transduces signal across the cell membrane

Question 26

Metabotropic Receptors - Transduce signals into the cell not directly through an ion channel but through activation of a …-… which in turn triggers a series of intracellular events (that can lead to ion channel opening)

Answer 26

Metabotropic Receptors - Transduce signals into the cell not directly through an ion channel but through activation of a G-protein which in turn triggers a series of intracellular events (that can lead to ion channel opening)

Question 27

Synaptic Second-messenger Systems

Answer 27

Question 28

Synaptic Second-messenger Systems

Answer 28

Question 29

G-proteins

• GTP–binding proteins composed of three subunits – a, b and g
  
  • 1) in resting state the heteromer is bound to GDP
  • 2) on binding of a ligand to the receptor the GDP is switched for a GTP and the heteromer splits in two
  • 3) the Ga subunit and Gbg complex divide and diffuse separately through the membrane
  • 4) these individual entities are able to stimulate activity of other effector proteins
  • 5) a subunits have intrinsic GTP-GDP enzymatic activity allowing the signal to be transient: the break down from GTP to GDP switches off its activity
  • 6) at this point the heteromer recomplexes and awaits activation by ligand binding to another receptor.

Answer 29

• GTP–binding proteins composed of three subunits – a, b and g
  
  • 1) in resting state the heteromer is bound to GDP
  • 2) on binding of a ligand to the receptor the GDP is switched for a GTP and the heteromer splits in two
  • 3) the Ga subunit and Gbg complex divide and diffuse separately through the membrane
  • 4) these individual entities are able to stimulate activity of other effector proteins
  • 5) a subunits have intrinsic GTP-GDP enzymatic activity allowing the signal to be transient: the break down from GTP to GDP switches off its activity
  • 6) at this point the heteromer recomplexes and awaits activation by ligand binding to another receptor.

Question 30

G-protein-coupled effector systems

• In comparison to the numbers of receptors there are relatively few G-proteins.
• a subunits (~20)
  
  • G.. stimulates adenylyl cyclase
  • G… inhibits adenylyl cyclase
  • G… stimulates phospholipase C
• bg complexes (5 b and 12 g)
  
  • Activate …+ channels directly (G-protein gated ion channel). This is the mode of action for muscarinic ACh receptors in the heart and the GABA(B)receptor.
  • (Relatively fast acting and local effect, “shortcut pathway”)

Answer 30

• In comparison to the numbers of receptors there are relatively few G-proteins.
• a subunits (~20)
  
  • Gs stimulates adenylyl cyclase
  • Gi inhibits adenylyl cyclase
  • Gq stimulates phospholipase C
• bg complexes (5 b and 12 g)
  
  • Activate K+ channels directly (G-protein gated ion channel). This is the mode of action for muscarinic ACh receptors in the heart and the GABA(B)receptor.
  • (Relatively fast acting and local effect, “shortcut pathway”)

Question 31

What is the shortcut pathway? (G-protein coupled effector system)

Answer 31

• Activate K+ channels directly (G-protein gated ion channel). This is the mode of action for muscarinic ACh receptors in the heart and the GABA(B)receptor.

(Relatively fast acting and local effect, “shortcut pathway”)

Question 32

Second messenger cascade

Answer 32

Question 33

Second messenger cascade - cAMP

• Gs and Gi have opposite effects on adenylyl cyclase, thus stimulating or inhibiting the synthesis of cAMP and the subsequent activation of protein kinase A (PKA).
  
  • GI - … adenylyl cyclase
  • GS - … it

Answer 33

• Gs and Gi have opposite effects on adenylyl cyclase, thus stimulating or inhibiting the synthesis of cAMP and the subsequent activation of protein kinase A (PKA).
  
  • GI - inhibits adenylyl cyclase
  • GS - stimulates it

Question 34

Second messenger cascades: PIP2

• G… activates phospholipase C (PLC) which converts PIP2 into IP3 and diacylglycerol (DAG). DAG activates protein kinase C (PKC) and IP3 releases Ca2+ from internal stores which activates Ca2+-dependent enzymes.

Answer 34

• Gq activates phospholipase C (PLC) which converts PIP2 into IP3 and diacylglycerol (DAG). DAG activates protein kinase C (PKC) and IP3 releases Ca2+ from internal stores which activates Ca2+-dependent enzymes.

Question 35

Kinases and phosphatases

• activity of many proteins regulated by their … state
• • maintenance of … state an important level of control
• e.g. … gated channels
  
  • Influences membrane potentials
  • and affects excitation state

Answer 35

• activity of many proteins regulated by their phosphorylation state
• • maintenance of phosphorylation state an important level of control
• e.g. Phosphorylation gated channels
  
  • Influences membrane potentials
  • and affects excitation state

Question 36

The same transmitter can have short- or long-term effects on an ion channel

Answer 36

Question 37

Amplification of G protein signals

• G-protein signalling provides a method of amplifying signals between neurons
• one transmitter bound receptor can uncouple … G-protein heteromers
• the signal can be … at every stage.
• what begins as a weak signal at the synapse can cause an amplified response in the … cell

Answer 37

• G-protein signalling provides a method of amplifying signals between neurons
• one transmitter bound receptor can uncouple multiple G-protein heteromers
• the signal can be amplified at every stage.
• what begins as a weak signal at the synapse can cause an amplified response in the postsynaptic cell

Question 38

What type of receptor can have an amplification of the signal?

Answer 38

metabotropic - due to g-protein coupled receptors

Question 39

Modulation by receptor activation

• Presynaptic receptors - change … of … released
  
  • autoreceptors regulate release of transmitter by modulating its synthesis, storage, release or reuptake - e.g. phosphorylation of tyrosine hydroxylase
  • heteroreceptors (axoaxonic synapses or extrasynaptic) - regulate synthesis and/or release of transmitters other than their own ligand
    
    • e.g. NE can influence the release of ACh by modulating α-adrenergic receptors
• Postsynaptic receptors - change … pattern or …
  
  • increase or decrease rate of cell firing (directly by action at ligand gated ion channels or indirectly G -protein or phosphorylation-coupled channels)
  • long term … changes

Answer 39

• Presynaptic receptors - change amount of transmitter released
  
  • autoreceptors regulate release of transmitter by modulating its synthesis, storage, release or reuptake - e.g. phosphorylation of tyrosine hydroxylase
  • heteroreceptors (axoaxonic synapses or extrasynaptic) - regulate synthesis and/or release of transmitters other than their own ligand
    
    • e.g. NE can influence the release of ACh by modulating α-adrenergic receptors
• Postsynaptic receptors - change firing pattern or activity
  
  • increase or decrease rate of cell firing (directly by action at ligand gated ion channels or indirectly G -protein or phosphorylation-coupled channels)
  • long term synaptic changes

Question 40

Modulation by receptor activation

• Presynaptic receptors - change amount of transmitter released
  
  • … regulate release of transmitter by modulating its synthesis, storage, release or reuptake - e.g. phosphorylation of tyrosine hydroxylase
  • … (axoaxonic synapses or extrasynaptic) - regulate synthesis and/or release of transmitters other than their own ligand
    
    • e.g. NE can influence the release of ACh by modulating α-adrenergic receptors
• Postsynaptic receptors - change firing pattern or activity
  
  • increase or decrease rate of cell firing (… by action at ligand gated ion channels or … G -protein or phosphorylation-coupled channels)
  • long term synaptic changes

Answer 40

• Presynaptic receptors - change amount of transmitter released
  
  • autoreceptors regulate release of transmitter by modulating its synthesis, storage, release or reuptake - e.g. phosphorylation of tyrosine hydroxylase
  • heteroreceptors (axoaxonic synapses or extrasynaptic) - regulate synthesis and/or release of transmitters other than their own ligand
    
    • e.g. NE can influence the release of ACh by modulating α-adrenergic receptors
• Postsynaptic receptors - change firing pattern or activity
  
  • increase or decrease rate of cell firing (directly by action at ligand gated ion channels or indirectly G -protein or phosphorylation-coupled channels)
  • long term synaptic changes

Question 41

Metabotropic receptors

• metabotropic … receptors
  
  • Group I: mGluR1+5 Gq
  • Group II: mGluR2+3 Gi
  • Group III: mGluR4,6,7+8 Gi
• …(B) receptor
• muscarinic acetylcholine receptors
• d… receptors
• noradrenergic and adrenergic receptors
• s… receptors
• n… receptors

Answer 41

• metabotropic glutamate receptors
  
  • Group I: mGluR1+5 Gq
  • Group II: mGluR2+3 Gi
  • Group III: mGluR4,6,7+8 Gi
• GABA(B) receptor
• muscarinic acetylcholine receptors
• dopamine receptors
• noradrenergic and adrenergic receptors
• serotonin receptors
• neuropeptide receptors

Question 42

Metabotropic receptors

• metabotropic g… receptors
  
  • Group I: mGluR1+5 Gq
  • Group II: mGluR2+3 Gi
  • Group III: mGluR4,6,7+8 Gi
• GABA(B) receptor
• muscarinic a… receptors
• dopamine receptors
• n.. and a… receptors
• serotonin receptors
• neuropeptide receptors

Answer 42

• metabotropic glutamate receptors
  
  • Group I: mGluR1+5 Gq
  • Group II: mGluR2+3 Gi
  • Group III: mGluR4,6,7+8 Gi
• GABA(B) receptor
• muscarinic acetylcholine receptors
• dopamine receptors
• noradrenergic and adrenergic receptors
• serotonin receptors
• neuropeptide receptors

Question 43

Other receptors found on or in neurons

• 1) …-linked receptors
  
  • e.g. Receptor tyrosine kinases
• Transmembrane proteins with intrinsic tyrosine kinase activity activated by neurotrophin binding (e.g. NGF, BDNF)
• On activation autophosphorylate
  
  • phosphorylate intracellular regulatory subunits
  • signal transduction cascades
• 2) … permeant signaling molecules activate intracellular receptors.

Answer 43

• 1) Enzyme-linked receptors
  
  • e.g. Receptor tyrosine kinases
• Transmembrane proteins with intrinsic tyrosine kinase activity activated by neurotrophin binding (e.g. NGF, BDNF)
• On activation autophosphorylate
  
  • phosphorylate intracellular regulatory subunits
  • signal transduction cascades
• 2) Membrane permeant signaling molecules activate intracellular receptors.

Question 44

Other receptors found on or in neurons

• 1) Enzyme-linked receptors
  
  • e.g. Receptor … kinases
• Transmembrane proteins with intrinsic … kinase activity activated by neurotrophin binding (e.g. NGF, BDNF)
• On activation autophosphorylate
  
  • phosphorylate intracellular regulatory subunits
  • signal transduction cascades
• 2) Membrane permeant signaling molecules activate intracellular receptors.

Answer 44

• 1) Enzyme-linked receptors
  
  • e.g. Receptor tyrosine kinases
• Transmembrane proteins with intrinsic tyrosine kinase activity activated by neurotrophin binding (e.g. NGF, BDNF)
• On activation autophosphorylate
  
  • phosphorylate intracellular regulatory subunits
  • signal transduction cascades
• 2) Membrane permeant signaling molecules activate intracellular receptors.

Question 45

Summary - Chemistry and Physiology of the Synapse

• Synaptic receptors:
  
  • recognize specific transmitters
  • activate effectors
• Typical effectors:
  
  • … channel (fast, brief, ms)
  • enzyme that produces … …
  • (sec – min, or days/weeks if gene transcription involved)
• … …:
  
  • A. trigger biochemical cascades by:
    
    • Activating specific protein kinases
    • Mobilizing …+ from intracellular stores
• Or
  
  • B. act on an ion channel (shortcut pathway)

Answer 45

• Synaptic receptors:
  
  • recognize specific transmitters
  • activate effectors
• Typical effectors:
  
  • ion channel (fast, brief, ms)
  • enzyme that produces second messenger
  • (sec – min, or days/weeks if gene transcription involved)
• Second messengers:
  
  • A. trigger biochemical cascades by:
    
    • Activating specific protein kinases
    • Mobilizing Ca2+ from intracellular stores
• Or
  
  • B. act on an ion channel (shortcut pathway)

Question 46

Summary - Chemistry and Physiology of the Synapse

• Synaptic receptors:
  
  • recognize specific transmitters
  • activate …
• Typical effectors:
  
  • ion channel (fast, brief, ms)
  • enzyme that produces second messenger
  • (sec – min, or days/weeks if gene transcription involved)
• Second messengers:
  
  • A. trigger biochemical cascades by:
    
    • Activating specific protein …
    • Mobilizing Ca2+ from intracellular stores
• Or
  
  • B. act on an ion channel (… pathway)

Answer 46

• Synaptic receptors:
  
  • recognize specific transmitters
  • activate effectors
• Typical effectors:
  
  • ion channel (fast, brief, ms)
  • enzyme that produces second messenger
  • (sec – min, or days/weeks if gene transcription involved)
• Second messengers:
  
  • A. trigger biochemical cascades by:
    
    • Activating specific protein kinases
    • Mobilizing Ca2+ from intracellular stores
• Or
  
  • B. act on an ion channel (shortcut pathway)

Question 47

• communication through … is regulated at multiple levels both pre- and post-synaptically.
• activation of receptors can modulate both electrical and structural properties of the neurons and synapse (neuro…)

Answer 47

• communication through synapses is regulated at multiple levels both pre- and post-synaptically.
• activation of receptors can modulate both electrical and structural properties of the neurons and synapse (neuroplasticity)