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Learning objectives for this module:
- Diversity and function of chemical synapses in brain
- Processes underlying excitability of neurons in the brain
- Compare and contrast synaptic transmission at GABA and glutamate synapses and to understand how synaptic 'modulators' work (eg. dopamine and acetylcholine)
- What info is carried by action potentials and how synaptic strength may be adjusted.
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Describe the process of propagating a nerve impulse through an action potential.
- Energy-dependent (by ATP) Na+/K+ pumps establish a resting potential of approx. -60mV potential difference across membrane - they are polarised.
- A stimulus will open these voltage-gated Na+ ion channels and creates a change in potential difference across membrane - depolarisation (will reach around +40 - go over threshold)
- Na+ channels now close and K+channels open, leading to diffusion of K+ ions out of neuron, again, creating repolarisation.
- K+ ions open/close slowly, so too much K+ ions diffuse out, causing hyperpolarisation, causing refractory period - ensures A.P only travels in one direction.
- K+ and Na+ diffuse out, facilitated by Na+/K+ pumps, resting potential restored.
- Action potential created by temporal and spatial summation of many inputs to dendrites that collectively create a graded response that determine whether an action potential will be initiated at the axon hillock or not.
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Inputs to dendrites may be either __ or __. What do the two mean?
- Inhibitory - they further hyperpolarise the neuron
- Excitatoy - they depolarise the neuron and bring the membrane potential closer to threshold
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Imagine cells in the retina.
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Imagine the cells in the cerebellum.
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What do GPCR stand for? Where are they found?
- G-protein coupled receptors
- Found in post-synaptic membrane
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What is the difference between a relative refractory period and absolute refractory period?
- ASK
- I think... Relative because a strong stimulus may still evoke action potential unlike during the absolute refractory period.
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The __ __ on axons greatly speeds conduction by propagating action potentials across different __ _ ___. This process is called ___ ___.
- myelin sheath
- nodes of Ranvier
- Salutatory conduction
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Action potentials carry info about __ of stimuli, their ___ and specific features (eg. __, __). Also what could be an underlying synaptic mechanism in memory formation and how is this created?
- timing
- intensity
- colour, saltiness etc
- Long-term potentiation (LTP)
- It is a persistent increase in synaptic strength following high-frequency stimulation of a chemical synapse.
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Give 3 types of synapses created by the presynaptic axon terminal making contact with different parts of the postsynaptic neuron.
- Axosomatic: axon terminal connects to soma
- Axodendritic: axon connects to dendrites
- Axoaxonic: axon-axon contact
- (In some specialised cells like in olfactory bulb, there are dendrodendritic synapses)
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What are the two types of synaptic potential and how can they affect the post-synaptic neuron?
- Excitatory post-synaptic potentials (EPSP): make te neuron more likely to fire action potential.
- Inhibitory post-synaptic potentials (IPSP): makes postsynaptic neuron less likely to generate action potential.
- [Positioning of each synapse determines impact of presynaptic activity on postsynaptic neuron]
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Especially in axoaxonic synapses, what does it mediate?
- Presynaptic inhibition
- Modulator cell regulates the ability of the presynaptic cell to release transmitter.
- Presynaptic facilitation also happens.
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Give a step-by-step explanation of how action potentials are transferred across synapses.
- 1. Action potential arrives at presynaptic terminal/synaptic knob
- 2. Opens voltage-gated calcium channels - Ca2+ ions enter terminal.
- 3. Ca2+ probably binds to Synaptotagmin (vesicle protein) which rapidly triggers vesicle fusion to membrane.
- 4. Fusion of vesicular (v) and terminal (t) membranes involves v-SNARE and t-SNARE proteins
- 5. Neurotransmitter (ACh - acetylcholine) is released through exocytosis of synaptic vesicles
- 6. ACh binds to sodium channel receptors in postsynaptic membrane, causing depolarisation
- 7. Depolarisation ends as ACh is broken down into acetate and choline by enzyme AChE (acetylecholinesterase). Others may be simply moved out by transporters.
- 8. Synaptic knob reabsorbs choline from synaptic cleft and uses it to synthesize new molecules of Ach
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Neurotransmitters in the synaptic cleft canalso diffuse in a __ manner to activate __ __ to inhibit what 3 possible things?
- retrograde
- presynaptic autoreceptors
- To inhibit...
- initiation of action potentials
- Neurotransmitter synthesis
- Neutransmitter release
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Which synaptic cleft is smaller? Chemical synapses or electrical gap junctions?
- At electrical gap junctions - 3nm
- Chemical synapses are 5nm-20nm
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Electrical synapses. How are they connected?
- Proteins called connexins span the gap junctions
- allowing ions to pass directly from cytoplasm of one cell to the cytoplasm of another
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Cells connected by gap junctions are said to be ...
- electrically-coupled
- because ionic conductance can pass through these channels
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What are the characteristics of an electrical synapse? (3)
- Fast
- Fail-safe
- Bidirectional
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Where are electrical synapses often found?
- In CNS where neighbouring cells need to be highly synchronised (eg. locus coeruleus in the Pons - involved in physiological responses to stress and panic)
- Also a lot during early embryonic dvelopment
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What are the advantages of chemical synapses? (6)
- Activate and inhibit post-synaptic neuron
- Unidirectional (important for synaptic plasiticity)
- Amplification by G-protein SM cascades
- Diversity (differing timescales etc)
- Rich opportunities for drug intervention
- Require strong stimuli
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What are the disadvantages of chemical synapses?
- Slower than electrical synapses (approx. 1000x slower)
- Unidirectional
- Desensitise with repeated stimulation
- Sensitise with repeated stimulation
- Susceptible to 'trojen horse' neurotoxins (ASK)
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Neurotransmitters bind to receptor proteins embedded in the __ __.
postsynaptic density
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What are theo broad types of receptors?
- Transmitter-gated ion channels (aka ionotropic receptors)
- G-protein-coupled receptors (GPCR) - aka metabotropic receptors
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Give 3 types of ionotropic (transmitter-gated ion channels)
- GABA-A receptors: (inhibitory) - GABA
- NMDA receptors: (excitatory) - glutamate (NMDA receptors also permeable to Ca2+ ions)
- Nicotinic receptors: (excitatory) - acetylecholine
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Give 2 examples of neurotransmitters/molecules stimulating GPCRs/metabotropic receptors.
- Acetylcholine on muscarinic receptors
- Dopamine on D1 and D2 receptors
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GPCRs (aka __ receptors) mediate __ and __-__ actions on the post-synaptic membrane.
- metabotropic receptors
- slower
- longer-lasting
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How do G-proteins work?
- GCPR activates small proteins called G-proteins
- which translocates along the intracellular surface of the membrane of the postsynaptic neuron to activate effector proteins.
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G-proteins have __ effects on ion channel permeability as well as variety of __ (eg.__ __) and __ __ __.
- diverse
- enzymes
- adenylate cyclase
- second messenger systems
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Imagine a diagram of the second messenger system.
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What is an important feature of GPCR's? Give an example.
- Signals can be greatly amplified.
- Eg. Retina - single activated rhodopsin molecule activates 150 G-proteins to cause closure of several hundred ion channels in photoreceptor.
- Allows for extraordinary sensitivity of rod photoreceptor cells under low light conditions.
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