Ch 13 neurons - Animal Physiology.txt

  1. Ch 13
  2. Advantages (and dis) of electrical synapses (CH 13Summary #1)
    • Role: Mediates Fast, synchronous action
    • Advantages
    • 1: current flow is INSTANTANEOUS
    • 2: current flows EITHER DIRECTION (not polarized)…could be DISadvantage
    • 3: Continuity between cells via GAP JXNS bridged by CONNEXON protein CHANNELS
    • Disadvantage
    • 1: Electrical synapses ALWAY Excitatory (not inhibitory)
  3. Chemical Synapses properties
    • 1: 20-30nm synaptic cleft connecting (barrier to DIRECT communication)
    • 2: Pre-synaptic bouton contains Neurotransmitter molecules stored in SYNAPTIC VESICLES
    • 3: Post-synaptic neuron holds RECEPTOR MOLECULES to bind to neurotransmitters
  4. Zones on a Synapse
    • Active zone: site of vesicle release
    • Post-synaptic densities: sites of high neurotransmitter RECEPTORs
    • Scaffold proteins: aid in organizing proteins and receptors at synapse
    • Dendritic spines: Site of Excitatory Synapses-Allow for INCREASED Surface Area for signals
  5. Steps involved in Chemical Synapse and 2 types of receptors (Ch 13 Summary #8)
    • 1. Ca enters: Action potential Depolarizes axon terminal OPENING Ca Channels for Ca Entry to cell
    • 2. Vesicle fusion: Ca ions trigger vesicles to fuse to active zones on bouton
    • 3. Ionotropic: Ion neurotransmitter receptors OPEN allowing IONS into post-synaptic cells (ie Na entry causes DEpolarization of post-syn)
    • 4. Metabotropic: Metabotropic receptors (GPCRs) are activated by neurotransmitters to initiate cascade of eents to produce 2nd messengers (cAMP)
  6. Advantages of Chem Synapses
    • 1: Can be excitatory OR inhibitory
    • 2: Can only interact ONE WAY
    • 3: AMPLIFICATION Of POST-Synaptic CURRENT Flow: release of vesicles and transmitters can open MANY channels to amplify
    • 4: MODIFIABLE in their properties (vs electrical syn)
  7. 2 Neurotransmitter effects
    • EPSP: Excitatory post-syn potential allows for Depolarization (ie: Glutamate - opens channels to allow for Na and K to go INTO post-syn cell)
    • IPSP: Inhibitory post-syn potential cause HYPERpolarization (ie: GABA diffuses to Post-syn membrane and allows for CHLORIDE ENTRY into Post-syn cell)
  8. Temporal and Spatial summation
    • Can combine both IPSP and EPSPs generated
    • temporal: combination of SAME nerve repeatedly stimulating rapidly
    • spatial: combination of simultaneous EPSPs occurring at DIFFERENT nerves
  9. Actions at neuromuscular jxn
    • Neurotransmitter is Acetylcholine (located in vesicles)
    • Diffuses into post-syn receptors where it BINDS
    • Allowing for Na entry into post-syn cell and K moves out (DEPOLARIZATION)
    • Action potential is Triggered!
    • REUPTAKE of ACh by Acetylcholinesterase breakdown into choline
    • Choline moves through choline transporter on pre-syn membrane
  10. Neuroreceptor release STEPS
    • 1. Tethering: Quanta packets move towards Active Zone, attaching REVERSIBLY to SNARE proteins on membrane
    • 2. Docking: Quanta vesicles bind to t- and v-SNARE IRREVERSIBLY
    • 3. Priming: Ca enters via channels (Depolarization causes this) and binds to Synaptotagmin..triggering
    • 4. Fusion: Ca-synaptotagmin causes CONFORMATIONAL change leading to fusion with the membrane and exocytosis of neurots
    • 5. Endocytosis of vesicle: ATP dependent with association of protein Clathrin
  11. Quanta
    Vesicles releasing neurotransmitters, each contain several 1000 neurotransmitters
  12. Neurotransmitter Example types
    • Small molecule neuotransmitters:
    • Acetylcholine and Glutamate (most fast EPSPs): ionotropic (causes EPSPs)
    • Dopamine: metabotropic (G protein - causes IPSPs)
    • GABA (most fast IPSPs): Ionotropic (causes IPSPs)
    • Also peptide neurotransmitters: multiple known
  13. Neuron and neurotransmitter release
    Neurons can release multiple neurotransmitters, usually 1 small molecule and multiple peptide transmitters
  14. Peptide vs Small molecule neurotransmitters
    • Peptide are produced in Neuronal cell body vs at axon terminal w others
    • Peptide inactivated by peptidases vs reuptake or enzymes w other
    • Peptide has HIGH freq stim vs slow w other
  15. Criteria for identifying if there is a NEUROTRANSMITTER at a particular site (Ch 13 SUMMARY #5)
    • 1. NT must be be PRESENT at pre-syn terminal and
    • 2. RELEASED upon pre-syn stimulation
    • 3. NT when added to extracell space must mimic effects of pre-syn stimulation
    • 4. MECHANISM for REMOVAL of NT should exist
    • 5. DRUG EFFECTS on NT may aid in determinig
  16. Why are there multiple receptor subtypes for each neurotransmitter? (Ch 13 SUMMARY #7)
    • Receptors are used to mediate MULTIPLE Effects, in some cases by the same receptors (ie; ACh receptors - example below)
    • ie: In Skeletal muscle, ACh receptor stimulated by nicotine (nicotinic receptor) works to aid in excitation via EPSPs
    • In heart muscle, ACh receptor stimulated by Muscarine (muscarinic receptor) aids in IPSPs
  17. Why are there so many neurotransmitters (evolutionarily) (Ch 13 SUMMARY #6)
    • There are evolutionary similarities among vertebrate also found in Nervous system of invertebrates (ie GABA, dopamine, seratonine)
    • These neurotransmitters have been evolutionarily conserved, but their ROLE may be different depending on the organism
    • Even peptide neutrotransmitters have been shown to have similar protein families showing their importance evolutionarily
  18. Ligand-gated Channel characteristics (ionotropic)
    • 1. Opening is ALL or NOTHING
    • 2. Probability of opening is DEPENDENT on NT
    • 3. Ionic current thru channel provides Synaptic POTENTIAL
    • 4. Currents can be SUMMATED to equal synaptic current
  19. Example of Ionotropic receptor
    • Nicotinic ACh receptor
    • Contains five alpha subunits surrounding ion channel
    • Requires binding of 2 NTs allowing opening to contribute to PSP
  20. Metabotropic vs ionotropic action difference
    • METABO: Indirect mode of action (GPCR). Produces Slow, but LONG Lasting effect
    • IONO: DIRECT mode of action (ion channels). Produces Fast, Short effects
  21. Example of Metabotropic receptor
    • Norepinephrine acts on GPCR
    • GPCR activates G-protein
  22. G-protein structure and role
    • has alpha, beta and gamma units
    • a-subunit releases GDP when activated, in exchange for GTP
    • a-subunit dissociates from rest and binds to adenlyl cyclase
    • cyclase converts ATP to cAMP
    • cAMP ACTIVATES cAMP protein kinases
    • These kinases PHOSPHORYLATE proteins, such as MEMBRANE, CYTO or NUCLEAR proteins
    • ION Channels: G-proteins can activate them DIRECTLY
  23. ACh inhibitory action example
    Muscarinic ACh receptors act as GPCRs to act with INHIBITORY action
  24. Habituation and Sensitization
    • Habit: DECREASE in reflex response when stimulus is repeated
    • Senz: ENHANCEMENT of reflex response to stimulus, when 2ND novel stimulus presented
    • ie Aplysia fish, gills amplitude of withdrawl diminishes with repeated repeated low freq stim but when hit on the head the response to stim of gills is large again
  25. How habituation and sensitization works (neuronal level)
    • Habit: DECREASE in QUANTA number (so less neurotransmitters released) due to Inactivation of Ca Channels
    • Senz: the sensitizing stimulus INCREASES Amount of NT released Per Impulse, due to INCREASED Ca Influx
    • BOTH
    • First, Ionotropic: Produces EPSPs, but ONLY work when post-syn is DEPOLARIZED (AMPA receptors aid in depolarization allowing Na entry)
    • ActioN: Glutamate activates NMDA receptor, but Mg blocks the ion channel. DEPOLarization causes release of Mg into synapse, and then Ca and Na can flow in (and K out)
    • Then, METABOTROPIC: The Ca that it allow into the post-syn cell acts as 2nd Messengers to activate Ca dependent protein kinases and allow more AMPA vesicles (containing AMPA glutamate receptors) to fuse to membrane to generate ENHANCED POST-SYN response
  27. Long term potentiation in hippocampus
    Long-lasting ENHANCEMENT of Synaptic transmission following INTENSE long-lasting stimulation
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Ch 13 neurons - Animal Physiology.txt