Neurotransmission and Neuromodulation Flashcards
List the structures of the neuron and their function
Dendrites: (“Dendron” = tree)
Recipient of information from other neurons. Large receptive field.
Soma (cell body):
Contains the machinery that controls processing in the cell and integrates information and Nucleus- containing DNA
Axon:
Carries information (action potential) from the soma to the terminal boutons and hence to other cells. Axons can branch to contact multiple neurones.
Axons can innervate neighbouring neurons or neurons far away.
Terminal boutons (buttons):
Found at the end of the axon, location of the synapse, communication point with other neuron
Structures of neuron sum
All this information integrated in the dendrite gets integrated in the soma and then once theres enough excitatory input, the neuron produces an action potential. This AP gets buried down the axon from the soma to the terminal boutons and to other cells. Axons can branch to contact multiple neurons.
What does the neuronal membrane do?
What makes up the membrane?
Neuronal membrane separates outside world of neuron from the inside world of the neuron.
It keeps certain substances out, this is how specific information can reach the neuron.
Boundary of soma, dendrites, axon & terminal boutons.
Its job is to separate the extracellular environment from the intracellular environment.
Membrane: Lipid bilayer (5nm)
The phospholipid molecules make up the membrane.
What do protein structures of the neuronal membrane do?
1- what do they detect?
2- allow…?
3- cytoskeletal?
4-
- what are proteins that reside in the membrane called and what do they do.
- what respond to these messages, called?
- what other structures do you have?
1- Detect substances outside of the cell
2- Allow access of certain substances into the cell (gated: chemical or electrical)
3- Cytoskeletal- connected to membrane, skeleton of the cell
4-
- Certain proteins reside in the membrane called receptors that detect chemical messengers.
- The transmembrane proteins respond to these messages, change confirmation, and then send signals to inside the cells, called metabotropic receptors.
- Then you have the donut like structures called ion channels, these have a pore that allow certain ions to pass through.
What are most chemicals in our body?
Most chemicals in our body are hydrophillic, and this membrane stops most of these substances from coming through.
(hydrophobic- afraid of water
hydrophilic- likes water)
What is the synapse?
The key sight for neuronal communication
What are the 2 types of synapse? refer to…
- commonality in adult mammalian neurons
- connections
- junction
- gap
- chemicals
-
Electrical synapse:
- Very rare in adult mammalian neurons (e.g. found in retina)
- direct connections- electrical activity is fast
- Junction between the neurons is very small (3nm – gap junction)
- Gap is spanned by proteins (connexins) which are used to communicate between the neurons (ions move freely) -
Chemical synapses: (more important)
- Common in adult mammalian neurons
- Junction between the neurons 20-50nm (synaptic cleft)
- Chemicals (neurotransmitters) are released from the presynaptic neuron to communicate with the postsynaptic neurones
Early experimental evidence for chemical transmission
1- who was it first demonstrated by?
2- alteration to HR?
3- what was substance ‘sufficient’ to do?
4- acceptance as?
1- First demonstrated by Loewi in the 1920s
2- Application of fluid following vagus nerve stimulation slowed down heart rate
3- Substance was ‘sufficient’ to change heart activity
4- Acceptance as primary means of communication in the brain in ’60s
Sum of experiment Loewi did
He said in frogs heart, if you stimulate the vagus nerve, usually the HR slows down. He says I’ll bet you theres something released. And whats released is responsible for making the HR go down. So…
- Stimulate vagus (donor heart)
- Heart rate slows (donor heart)
- Remove fluid sample (donor heart)
- Add fluid to recipient heart
- Heart rate slows
What are the synaptic locations?
Axodendritic (most common):
Presynaptic neuron (efferent) sends its axon and terminal boutons to the dendrite of post synaptic neuron.
Axosomatic:
Axon goes to the soma (seen in inhibitory)
Axoaxonic:
Axon impinges on another axon and modulates the signal- you can excite/ inhibit the other axon
Chemical transmission process of events
- Neurotransmitter (NT) synthesis, transport & storage
- Depolarization (action potential)
- Open voltage-gated Ca2+ channel (sensitive to changes in voltage)
- Ca2+ influx (coming in)
- Movement and docking of vesicles (migrate)
- Exocytosis-diffusion (release the contents)
7+8. Interact with receptors
In/deactivation of NTs- starting cascading events
(Eventually these NTs have to be turned off)
What are neurotransmitters?
Chemicals that are used to transmit information from the presynaptic neuron to the postsynaptic neuron.
Criteria for neurotransmitter?
- Chemical synthesised presynaptically.
- Electrical stimulation leads to the release of the chemical.
- Chemical produces physiological effect
- Terminate activity
Postsynaptic action of the Neurotransmitter
Neurotransmitter binds to receptors on the postsynaptic membrane, which affects the activity of the postsynaptic cell. The configuration of the receptors make them specific for different neurotransmitters.
What are the two types of receptors and their functions
Ionotropic receptor
- Opening of an ionic channel (typically).
- Allow ions
Metabotropic receptor
- Activates an internal 2nd messenger systems that goes on to affect the functioning of the postsynaptic cells
- It takes more time
- Through a cascade of events, theres an effector protein which uses second messages and creates these events and modifies
Action of neurotransmitters at receptors
What do receptors vary in their?
- Pharmacology – what transmitter binds to the receptor and how drugs interact
- Agonist – a drug (or endogenous ligand/neurotransmitter) that can combine with a receptor on a cell to produce a cellular reaction
- Antagonist – a drug that reduces or completely blocks the activity of the agonist or endogenous ligand, no cellular effect after interacting with receptor - Kinetics – rate of transmitter binding and channel gating determine the duration of effects
(how fast does that receptor opens up/ closes) - Selectivity – what ions are fluxed (Na+, Cl-, K+ and/or Ca2+)
- Conductance – the rate of flux
What happens when…
1. agonist acts alone
2. agonist acts with antagonist
3. antagonist alone
- agonist alone → full activation
- agonist + antagonist → less activation
- antagonist alone → no activation
Ionotropic receptors
- what does fast transmission mean?
- explain excitatory fast transmission
- explain inhibitory fast transmission
Excitatory fast transmission:
- Ion channel opens
- Movement of positive ions into the neurone (Na+)
(e.g. Glutamate receptors)
- Depolarisation
- Excitatory post synaptic potential (EPSP)
- Membrane potential (voltage) goes up and is positive
Inhibitory fast transmission:
- Ion channel opens
- Movement of negative ions into the neurone (Cl-)
(e.g. GABAA receptors)
- Hyperpolarisation
- Inhibitory post synaptic potential (IPSP)
- Membrane potential goes down- negative
Activation of a G-protein coupled receptor:
- Neurotransmitter binds to receptor and activates the G-protein (exchange GDP for GTP - once you have this GTP, one of the sub-units breaks apart, is activated and modulates other protein)
- G protein splits and activates other enzymes
- The breakdown of GTP turns off G protein activity (effector proteins- these proteins cause another cascade and tend to amplify things)
- Series of chemical reactions that leads to an amplification of the signal – second messenger system
