PBS2 - Molecules and Synapses Pt1

  1. 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.
  2. 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.
  3. 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
  4. Imagine cells in the retina.
    Image Upload 2
  5. Imagine the cells in the cerebellum.
    Image Upload 4
  6. What do GPCR stand for? Where are they found?
    • G-protein coupled receptors
    • Found in post-synaptic membrane
  7. 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.
  8. The __ __ on axons greatly speeds conduction by propagating action potentials across different __ _ ___. This process is called ___ ___.
    • myelin sheath
    • nodes of Ranvier
    • Salutatory conduction
  9. 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.
  10. 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)
  11. 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]
  12. 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.
  13. 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
  14. 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
  15. Which synaptic cleft is smaller? Chemical synapses or electrical gap junctions?
    • At electrical gap junctions - 3nm
    • Chemical synapses are 5nm-20nm
  16. 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
  17. Cells connected by gap junctions are said to be ...
    • electrically-coupled
    • because ionic conductance can pass through these channels
  18. What are the characteristics of an electrical synapse? (3)
    • Fast
    • Fail-safe
    • Bidirectional
  19. 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
  20. 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
  21. 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)
  22. Neurotransmitters bind to receptor proteins embedded in the __ __.
    postsynaptic density
  23. What are theo broad types of receptors?
    • Transmitter-gated ion channels (aka ionotropic receptors)
    • G-protein-coupled receptors (GPCR) - aka metabotropic receptors
  24. 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
  25. Give 2 examples of neurotransmitters/molecules stimulating GPCRs/metabotropic receptors.
    • Acetylcholine on muscarinic receptors
    • Dopamine on D1 and D2 receptors
  26. GPCRs (aka __ receptors) mediate __ and __-__ actions on the post-synaptic membrane.
    • metabotropic receptors
    • slower
    • longer-lasting
  27. 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.
  28. G-proteins have __ effects on ion channel permeability as well as variety of __ (eg.__ __) and __ __ __.
    • diverse
    • enzymes
    • adenylate cyclase
    • second messenger systems
  29. Imagine a diagram of the second messenger system.
    Image Upload 6
  30. 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.
Author
master.director2
ID
298823
Card Set
PBS2 - Molecules and Synapses Pt1
Description
Molecules and synapses
Updated