PBS2 - Molecules and Synapses Pt1
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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.
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.
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
Imagine cells in the retina.
Imagine the cells in the cerebellum.
What do GPCR stand for? Where are they found?
- G-protein coupled receptors
- Found in post-synaptic membrane
What is the difference between a relative refractory period and absolute refractory period?
- I think... Relative because a strong stimulus may still evoke action potential unlike during the absolute refractory period.
The __ __ on axons greatly speeds conduction by propagating action potentials across different __ _ ___. This process is called ___ ___.
- myelin sheath
- nodes of Ranvier
- Salutatory conduction
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?
- colour, saltiness etc
- Long-term potentiation (LTP)
- It is a persistent increase in synaptic strength following high-frequency stimulation of a chemical synapse.
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)
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]
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.
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
Neurotransmitters in the synaptic cleft canalso diffuse in a __ manner to activate __ __ to inhibit what 3 possible things?
- presynaptic autoreceptors
- To inhibit...
- initiation of action potentials
- Neurotransmitter synthesis
- Neutransmitter release
Which synaptic cleft is smaller? Chemical synapses or electrical gap junctions?
- At electrical gap junctions - 3nm
- Chemical synapses are 5nm-20nm
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
Cells connected by gap junctions are said to be ...
- because ionic conductance can pass through these channels
What are the characteristics of an electrical synapse? (3)
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
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
What are the disadvantages of chemical synapses?
- Slower than electrical synapses (approx. 1000x slower)
- Desensitise with repeated stimulation
- Sensitise with repeated stimulation
- Susceptible to 'trojen horse' neurotoxins (ASK)
Neurotransmitters bind to receptor proteins embedded in the __ __.
What are theo broad types of receptors?
- Transmitter-gated ion channels (aka ionotropic receptors)
- G-protein-coupled receptors (GPCR) - aka metabotropic receptors
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
Give 2 examples of neurotransmitters/molecules stimulating GPCRs/metabotropic receptors.
- Acetylcholine on muscarinic receptors
- Dopamine on D1 and D2 receptors
GPCRs (aka __ receptors) mediate __ and __-__ actions on the post-synaptic membrane.
- metabotropic receptors
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.
G-proteins have __ effects on ion channel permeability as well as variety of __ (eg.__ __) and __ __ __.
- adenylate cyclase
- second messenger systems
Imagine a diagram of the second messenger system.
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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