Lecture 4 : Synaptic transmission part 2
Control of transmitter activity in the synaptic cleft
1) Reuptake
● Norepinephrine and Glutamate are taken up into the presynaptic cell
● Glutamate is taken through Na+ linked transport, both into neurons and astrocytes
2) Deactivation
● Acetylcholine is digested by cholinesterase
● Norepinephrine is deactivated by catechol-O-methyl-transferase (COMT) & cleared into blood
circulation
● Neuropeptides action is terminated by proteolysis or by diffusion away from the postsynaptic
membrane
Glial presence at synaptic level
- astrocytes do not fire AP, but are Ca2+ excitable
- 1 astrocyte contacts 1000s of synapses !!
- Astrocytes ‘ listen ‘ to neurons (all major receptors present on astrocytes)
- Astrocytes release neurotransmitters (Glu, ATP,...)
- Astrocytes modulate neuronal excitability and synaptic transmission
Fast Chemical Synapses Slow Chemical Synapses Intermediate Chemical Synapses
Neurotrans synt in presynaptic terminal Neurotrans synt in presynaptic terminal
small mol, stored in small vesicles large mol, stored in large vesicles
e.g. Ach GABA e.g. peptides amines
Vesicles are located near plasma membrane Vesicles are located further away from the terminal
(active zone) Released sites are to the side of the terminal
Ligand gated ion channel G-prot signaling through 2nd messenger cascade G prot
e.g. nicotonic AchR, stimulated by Na+ influx e.g. b-adrenergic receptor, stim by Ca2+ channels e.g. muscarinic AchR, inhibit by
activation of K+ channel
1
, Transmitter effects on ion channels
● Divergence
○ one transmitter (NE) → activate > receptors → stim diff G prot/ second messengers →
increase/ decrease the gating of many types of ion channels
● Convergence
○ diff transmitters bind to their specific receptors, same or diff 2nd messenger systems, influence
the same set of ion channels
Synaptic connections/ networks
● Spatially focused
○ Brain carries out many sensory/ motor/ cognitive functions that requires fast/ specific/ spatially
organized neural connections and operations
● Widely divergent
○ more general changes in the brain (waking up/sleeping)
● Modulatory system w diffuse central connections
○ Neurons of the diffuse systems arise from the central core of the brain, most of them from the
brainstem (typically, several thousand)
○ Each neuron can influence many others bc each one has an axon that may contact more than
100’000 postsynaptic neurons spread widely across the brain
○ The synapses made by some of these systems seem designed to release transmitter
molecules into the extracellular fluid so that they can diffuse to many neurons rather than be
confined to the vicinity of a single synaptic cleft - volume transmission
● Separate syst :
○ use
■ norepinephrine
■ serotionine (5-hydroxytryptamine 5-HT)
■ dopamine
■ Ach
■ histamine
○ involved metabotropic transmitter receptors
■ coupled to enzyme e.g. adenylyl cyclase or Phospholipase C through G prot
■ barin has 10 to 100 more metabotropic (muscarinic) Ach receptor than inotropic
(nicotinic) Ach receptor
● Chemical substance that function as Synaptic Transmitters
○ neurotransmitter
■ stimulate the primary postsynaptic response
● released during activity of presynaptic neuron
● effects on postsynaptic cell and on the presynaptic cell
● Action at synapse is blocked by antagonists
■ small molec., rapid acting
● transmission of sensory signals to the brain & of motor signals back to
muscle
⇒ STORED IN SYNAPTIC VESICLE, RELEASED BY CA2+ EXOCYTOSIS
● Acetylcholine
● Amino Acids
○ Gamma-aminobutyric acid (GABA)
○ Glycine
○ Glutamate
○ Aspartate
● Purines
○ ATP
○ Adenosione
● Amines
● Serotonin
● Histamine
2
Control of transmitter activity in the synaptic cleft
1) Reuptake
● Norepinephrine and Glutamate are taken up into the presynaptic cell
● Glutamate is taken through Na+ linked transport, both into neurons and astrocytes
2) Deactivation
● Acetylcholine is digested by cholinesterase
● Norepinephrine is deactivated by catechol-O-methyl-transferase (COMT) & cleared into blood
circulation
● Neuropeptides action is terminated by proteolysis or by diffusion away from the postsynaptic
membrane
Glial presence at synaptic level
- astrocytes do not fire AP, but are Ca2+ excitable
- 1 astrocyte contacts 1000s of synapses !!
- Astrocytes ‘ listen ‘ to neurons (all major receptors present on astrocytes)
- Astrocytes release neurotransmitters (Glu, ATP,...)
- Astrocytes modulate neuronal excitability and synaptic transmission
Fast Chemical Synapses Slow Chemical Synapses Intermediate Chemical Synapses
Neurotrans synt in presynaptic terminal Neurotrans synt in presynaptic terminal
small mol, stored in small vesicles large mol, stored in large vesicles
e.g. Ach GABA e.g. peptides amines
Vesicles are located near plasma membrane Vesicles are located further away from the terminal
(active zone) Released sites are to the side of the terminal
Ligand gated ion channel G-prot signaling through 2nd messenger cascade G prot
e.g. nicotonic AchR, stimulated by Na+ influx e.g. b-adrenergic receptor, stim by Ca2+ channels e.g. muscarinic AchR, inhibit by
activation of K+ channel
1
, Transmitter effects on ion channels
● Divergence
○ one transmitter (NE) → activate > receptors → stim diff G prot/ second messengers →
increase/ decrease the gating of many types of ion channels
● Convergence
○ diff transmitters bind to their specific receptors, same or diff 2nd messenger systems, influence
the same set of ion channels
Synaptic connections/ networks
● Spatially focused
○ Brain carries out many sensory/ motor/ cognitive functions that requires fast/ specific/ spatially
organized neural connections and operations
● Widely divergent
○ more general changes in the brain (waking up/sleeping)
● Modulatory system w diffuse central connections
○ Neurons of the diffuse systems arise from the central core of the brain, most of them from the
brainstem (typically, several thousand)
○ Each neuron can influence many others bc each one has an axon that may contact more than
100’000 postsynaptic neurons spread widely across the brain
○ The synapses made by some of these systems seem designed to release transmitter
molecules into the extracellular fluid so that they can diffuse to many neurons rather than be
confined to the vicinity of a single synaptic cleft - volume transmission
● Separate syst :
○ use
■ norepinephrine
■ serotionine (5-hydroxytryptamine 5-HT)
■ dopamine
■ Ach
■ histamine
○ involved metabotropic transmitter receptors
■ coupled to enzyme e.g. adenylyl cyclase or Phospholipase C through G prot
■ barin has 10 to 100 more metabotropic (muscarinic) Ach receptor than inotropic
(nicotinic) Ach receptor
● Chemical substance that function as Synaptic Transmitters
○ neurotransmitter
■ stimulate the primary postsynaptic response
● released during activity of presynaptic neuron
● effects on postsynaptic cell and on the presynaptic cell
● Action at synapse is blocked by antagonists
■ small molec., rapid acting
● transmission of sensory signals to the brain & of motor signals back to
muscle
⇒ STORED IN SYNAPTIC VESICLE, RELEASED BY CA2+ EXOCYTOSIS
● Acetylcholine
● Amino Acids
○ Gamma-aminobutyric acid (GABA)
○ Glycine
○ Glutamate
○ Aspartate
● Purines
○ ATP
○ Adenosione
● Amines
● Serotonin
● Histamine
2
