L1 Neurotransmitter release - Jon Robbins
• Give an overview of the events of neurotransmitter release during synaptic
Transmission DONE
• Describe how drugs may affect neurotransmission
L2 Introduction to Glia- Sarah Thomas
• Explain the distinction between neurons and glial cells
• Describe the main types of glia in the CNS and PNS, their lineages and functions
CNS
Microglia: immune system of the brain, activated by injury and disease,
mesodermal origin, Amoeboid multiply in corpus callosum - called
fountains of microglia that then migrate to brain
Astrocytes: structural support, homeostasis, enwrap blood brain barrier,
injury response, form continuous syncytium,
- Of ectodermal origin- Intermediate progenitor cells form
astrocytes, equal probability of becoming macroglia or microglia
Oligodendrocytes: Relatively few and short processes – flat sheets that end in a myelin sheath
wrapped around an axon, of ectodermal origin, one can myelinate many axons
,NG2: derive from oligodendrocyte precursor cells, form synapses with neurons
PNS
Schwann cells: myelinating and non-myelinating, if axons are smaller than 1 micrometer then they
form a nonmyelinating schwann cell = radial sorting, depend on contact with axon
• Distinguish between ‘wiring' and ‘volume' transmission in the nervous system and
describe their roles
Wiring signalling is local one cell to the next very fast transmission, localized responses, precise
signalling
Volume is one cell releasing signal into extracellular fluid - diffuses and has action on cell further
away from original cell, communication beyond cleft
• Can act on one cell or population of cells
• It’s quite slow minutes to hours
• Another type: intracellular volume transmission- signal distributed through intracellular fluid
instead of extra - passes through gap junction
• Describe the main types of glial ion channels, water channels, and receptors
- AQP4 water channels- Any water added to the extracellular fluid is removed by astrocytes
because they express aquaporin 4 water channels
• Outline the mechanisms by which calcium waves can spread between astrocytes
Astrocytes: each astrocyte connected by gap junctions
Calcium propagation is not passing through cell gap junctions; its a second messenger called
InsP3 or via ATP receptors,
Calcium is signalling molecule forcing ATP to be released into extracellular fluid
ATP acts on receptors in neighboring cell through gap junctions stimulating InsP3 increasing
calcium in next cell
So ... Calcium leads to ATP released and into next cell leading to InsP3 which leads to calcium
once again --> NOT CALCIUM PASSED FROM CELL TO CELL
Gap junctions = insp3
Extracellular = ATP
• Outline the main functions of glia cells
,2. Buffering= regulating potassium since it can pass through syncytium wave, pH, water reg
Co2 passively diffuses into astrocyte - high carbonic anhydrase
• Allows co2 to form with water to form carbonic acid which dissociates into hydrogen and
bicarbonate which can go back out of the astrocyte
• This moves co2 away from neuronal activate by distributing hydrogen and bicarbonate into
extracellular fluid
3. Glutamate is easily taken up by astrocyte where it is converted into glutamine by glutamine
synthetase and taken into presynaptic terminal - Becomes glutamate or GABA again and enters
vesicles
4. End feet of astrocytic processes cover the whole capillary wall - which allows to maintain blood
brain barrier
5. In astrocyte it undergoes glycolysis to form lactate due to LDH5
• Lactate passes into extracellular fluid through MCT-1
o This makes it enter neuron through MCT-2
• Glut3 and MCT-2 form energy substrate (lactate and glucose in presynaptic terminal)
6. Astrocytes produce vasodilators or vasoconstrictors
7. Reactive astrogliosis: defensive reaction to isolate damaged area from the tissues of CNS- THIS IS
GLIA SCAR
L3 Transporters - Sarah Thomas
• Mechanisms of movement across membrane
, • Review the classes and topologies and location of the major neurotransmitter transporters
and vesicular transporters
Neurotransmitter transporters:
1. Plasma membrane- terminate synaptic transmission, recycling of transmitter molecules
a. Sodium chlorine depent transport
i. Serotonin - 5ht
ii. Nora
iii. Dopamine
iv. Gaba
v. Glycine
c. Sodium potassium dependent transp
a. EAA - glutamate
d. Vesicular – storage, vesicular membrane Vmat, VIAAT
• Explain the role of presynaptic neurotransmitter
reuptake
- regulates the level of neurotransmitter present
in the synapse, thereby controlling how long a
signal resulting from neurotransmitter release
lasts.
- Energy coupled with 2 sodiums down its conc
gradient
- Counter transport with potassium and hydroxyl
• Explain the role of glial cell neurotransmitter reuptake, with particular reference to the
glutamate shuttle
Glutamate shuttle
- Glutamate is too excitatory to be reuptake like others
- Goes into glial cells via EEATs– converted from glutamate to glutamine
- Glutamine can enter pre-synaptic neuron due to A transporter
- In presynaptic cleft converted back to glutamate
-
• Explain the role of neurotransmitter transporters in non-vesicular (calcium-independent)
neurotransmitter release
transporter reversal facilitates the release of
neurotransmitters into the synaptic cleft,
resulting in a higher concentration of synaptic
neurotransmitters and increased signaling
through the corresponding neurotransmitter
receptors
• Give an overview of the events of neurotransmitter release during synaptic
Transmission DONE
• Describe how drugs may affect neurotransmission
L2 Introduction to Glia- Sarah Thomas
• Explain the distinction between neurons and glial cells
• Describe the main types of glia in the CNS and PNS, their lineages and functions
CNS
Microglia: immune system of the brain, activated by injury and disease,
mesodermal origin, Amoeboid multiply in corpus callosum - called
fountains of microglia that then migrate to brain
Astrocytes: structural support, homeostasis, enwrap blood brain barrier,
injury response, form continuous syncytium,
- Of ectodermal origin- Intermediate progenitor cells form
astrocytes, equal probability of becoming macroglia or microglia
Oligodendrocytes: Relatively few and short processes – flat sheets that end in a myelin sheath
wrapped around an axon, of ectodermal origin, one can myelinate many axons
,NG2: derive from oligodendrocyte precursor cells, form synapses with neurons
PNS
Schwann cells: myelinating and non-myelinating, if axons are smaller than 1 micrometer then they
form a nonmyelinating schwann cell = radial sorting, depend on contact with axon
• Distinguish between ‘wiring' and ‘volume' transmission in the nervous system and
describe their roles
Wiring signalling is local one cell to the next very fast transmission, localized responses, precise
signalling
Volume is one cell releasing signal into extracellular fluid - diffuses and has action on cell further
away from original cell, communication beyond cleft
• Can act on one cell or population of cells
• It’s quite slow minutes to hours
• Another type: intracellular volume transmission- signal distributed through intracellular fluid
instead of extra - passes through gap junction
• Describe the main types of glial ion channels, water channels, and receptors
- AQP4 water channels- Any water added to the extracellular fluid is removed by astrocytes
because they express aquaporin 4 water channels
• Outline the mechanisms by which calcium waves can spread between astrocytes
Astrocytes: each astrocyte connected by gap junctions
Calcium propagation is not passing through cell gap junctions; its a second messenger called
InsP3 or via ATP receptors,
Calcium is signalling molecule forcing ATP to be released into extracellular fluid
ATP acts on receptors in neighboring cell through gap junctions stimulating InsP3 increasing
calcium in next cell
So ... Calcium leads to ATP released and into next cell leading to InsP3 which leads to calcium
once again --> NOT CALCIUM PASSED FROM CELL TO CELL
Gap junctions = insp3
Extracellular = ATP
• Outline the main functions of glia cells
,2. Buffering= regulating potassium since it can pass through syncytium wave, pH, water reg
Co2 passively diffuses into astrocyte - high carbonic anhydrase
• Allows co2 to form with water to form carbonic acid which dissociates into hydrogen and
bicarbonate which can go back out of the astrocyte
• This moves co2 away from neuronal activate by distributing hydrogen and bicarbonate into
extracellular fluid
3. Glutamate is easily taken up by astrocyte where it is converted into glutamine by glutamine
synthetase and taken into presynaptic terminal - Becomes glutamate or GABA again and enters
vesicles
4. End feet of astrocytic processes cover the whole capillary wall - which allows to maintain blood
brain barrier
5. In astrocyte it undergoes glycolysis to form lactate due to LDH5
• Lactate passes into extracellular fluid through MCT-1
o This makes it enter neuron through MCT-2
• Glut3 and MCT-2 form energy substrate (lactate and glucose in presynaptic terminal)
6. Astrocytes produce vasodilators or vasoconstrictors
7. Reactive astrogliosis: defensive reaction to isolate damaged area from the tissues of CNS- THIS IS
GLIA SCAR
L3 Transporters - Sarah Thomas
• Mechanisms of movement across membrane
, • Review the classes and topologies and location of the major neurotransmitter transporters
and vesicular transporters
Neurotransmitter transporters:
1. Plasma membrane- terminate synaptic transmission, recycling of transmitter molecules
a. Sodium chlorine depent transport
i. Serotonin - 5ht
ii. Nora
iii. Dopamine
iv. Gaba
v. Glycine
c. Sodium potassium dependent transp
a. EAA - glutamate
d. Vesicular – storage, vesicular membrane Vmat, VIAAT
• Explain the role of presynaptic neurotransmitter
reuptake
- regulates the level of neurotransmitter present
in the synapse, thereby controlling how long a
signal resulting from neurotransmitter release
lasts.
- Energy coupled with 2 sodiums down its conc
gradient
- Counter transport with potassium and hydroxyl
• Explain the role of glial cell neurotransmitter reuptake, with particular reference to the
glutamate shuttle
Glutamate shuttle
- Glutamate is too excitatory to be reuptake like others
- Goes into glial cells via EEATs– converted from glutamate to glutamine
- Glutamine can enter pre-synaptic neuron due to A transporter
- In presynaptic cleft converted back to glutamate
-
• Explain the role of neurotransmitter transporters in non-vesicular (calcium-independent)
neurotransmitter release
transporter reversal facilitates the release of
neurotransmitters into the synaptic cleft,
resulting in a higher concentration of synaptic
neurotransmitters and increased signaling
through the corresponding neurotransmitter
receptors
