Lecture 6

Synapses, continued

 
 

• vesicle has synaptotagmin (synaptic vesicle protein)
  
  • can interact with syntaxin (protein in neurolemma), interact only after priming of vesicle
    
• if put calcium in, it will come down and bind to synaptotagmin, changes the shape of synaptotagmin and can now interact with syntaxin, this causes the vesicle to open and NT is released
  
• synaptotagmin can bind to clathrin which is found surrounding the vesicle, when this binds it causes endocytosis or pulling away of the vesicle and the closing of the vesicle
  
• Ca can be pumped out by ATP-powered pumps, but typically think there is 3 Na in for one Ca out called an antiport
  
  • functions to remove most of the Ca
    
• Ca can also be taken up by mitochondria in the synaptic knob
  

   
   

• Autonomic Varicosities
  
  • receptors all over the cells, varicosities rain there NT around the receptors
    
  • use similar method to synaptic knob to release NT
    
  • takes time for NT to cross the synaptic cleft this delay is called the synaptic delay
    
  • the more synapses between start/end of excitation and wherever sending the impulse, the slower the signal will go
    
  • like reflexes to go through one or two synapses, so they go as fast as possible
    
  • response to NT, is dependent upon the receptor that the NT hits
    
    • Response not based on neurotransmitter
      
• if have excitatory receptor, bringing closer to threshold called Excitatory Post Synaptic Potential (EPSP)
  
  • EPSP's typically Na and Ca channels opening
    
  • Can also get EPSP by K channels closing
    
• if have an inhibitory receptor, bringing further away from threshold called Inhibitory Post Synaptic Potential (IPSP)
  
  • IPSP get closing of Na and Ca channels
    
  • opening of K channels, sometimes also see opening of Cl channels (Cl follows Na around, when Na pumped out Cl went without, have higher level of Cl outside of cell and whne open these channels, Cl flows in and hyperpolarizes the cell)
    
• sometimes see synaptic knob with another synaptic knob on top of it, the synaptic knob on top is regulating the amount of NT coming out of the second one
  
  • Synaptic knob on top is called presyanptic facilitation or presynaptic inhibition
    
• Presynaptic facilitation will increase the amount of NT leaving and it does this by either opening more Ca channels or prolonging how long the Ca channels are held open
  

  -can also close K channels, if it closes K channels, this will enhance action potential and will kick out more Ca
  

• Presyanptic inhibition will close the Ca channels, restrict them so they can't let in as much Ca, dampen action potential (if dampen the action potential, they will then open Cl channels, influx a negative)
  

 
 

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• A wants to get X to fire:
  
  • sends excitation
    
  • Doesn't work…fires again….doesnt work…..
    
  • NEEDED rapid firing
    
    • TEMPORAL Summation
      
• B wants Y to fire
  
  • Needs C to fire at same time to cause firing.
    
    • SPACIAL Summation
      

       
       

• temporal summation = rapid firing of two or more neurons or an individual neurons that causes excitation
  
  • temporal rapid firing can be adjusted, but with temporal firing all you can send is I fired
    
  • temporal summation in bursts used to send messages is called temporal patterning
    

     
     

• spatial summation = not rapid firing, but neurons fire once and then firing across three or more neurons is summed to achieve excitation
  
  • spatial pattern = tells you which neurons are firing
    
    • detect smell through spatial patterning
      
    • 10,000 odors spatially patterned in brain
      
      • when have a twitch fire a summation
        
      • summation in a multipolar neuron is in the axon hillock (where dendritic positives and negatives get summed), multipolar neuron will taper down to become an axon, this is the first initial segment of axon
        
      • unipolar and bipolar neurons summation occurs at the initial segment of the axon
        
      • to send a message regulate firing rate and how often it occurs
        

     
     

   
   

• NT made up in soma
  
  • sent down a microtubule railway microtubules
    
    • have vesicles attached to them which move back and forth
      

       
       

• protein called kinesin moves vesicle towards the synapse
  
  • Calcium combined with calmodulin will cause phosphorolation of vessle and release NT in synapse
    
  • Antegrade transport
    
• protein called dynein moves vesicle back up the microtubule to the soma to be refilled
  
  • Retrograde transport
    
• each of the microtubules have both proteins associated with it but only one works at a time
  
• some neurons have co-transmitters
  
  • don't come out of active sites, can come out anywhere around the synaptic knob
    
  • typically think they facilitate the main NT in some way, but they are not necessarily all the way
    
  • can enhance the NT when excitation high or low it depends on the neuron
    
  • Neuron needs certain firing rate to release co-transmitters (maybe)
    

     
     

NEUROTRANSMITTERS & RECEPTORS

• See Handout!!
  

   
   

• if NT binds directly to receptor and opens the channel  ionotropic receptor
  
  • NT directly opens/closes channel
    
• If NT activates a secondary messenger and is linked to something else 
  metabotropic
  
  • NT can hit a receptor, but it causes a metabolite to increase/decrease and can open/close a channel
    
  • two major metabotropic systems
    
    • cyclic AMP
      
      • See handout...
        
    • IP3-DAG
      
      • See handout...
        

 
 

Name	Chemical	Receptor	Receptor Type
Acetylcholine	Esther	Nicotonic – receptor find on skeletal muscle (5) Muscarinic M1-M5	1. Ionotropic     Metabotropic
Norepinephrine	Catecholamine	α 1-2 β 1-3	Metabotropic Metabotropic
Dopamine	Catecholamine	D 1-5	Metabotropic
Serotonin (5-hydro trptomine = 5-HT))	Indolamine	5-HT 3 5-HT 1, 3, 4-7	2. Ionotropic Metabotropic	Opens non selective channel
Histamine	Indolamine	H1-H3	Metabotropic	H3 in synaptic knob
GABA (gamma amino butyric acid)	Amino Acid	GABA A GABA B	3. Ionotropic Metabotropic	Opens Cl channel = inhib
Glycine	Amino Acid	Glycine Receptor NMDA	4. Ionotropic 5. Ionotropic	Opens Cl channel = inhib Has to bind BOTH gly/glut
Glutamate	Amino Acid	AMPA Kainate Metabotropic Receptor of Glutamate (11 subtypes) NMDA	6. Ionotropic 7. Ionotropic Metabotropic     5. Ionotropic	Opens Na channel Opens Na channels         Has to bind both glycine and glutamate
Endorphins/Enkephalins	Peptides	μ (mu) κ (kappa) δ (delta)	Metabotropic Metabotropic Metabotrpic	All called opiate receptors
Substance P/Neurokinate	Peptide	NK-1 Receptor	Metabotropic
Somatostatin (SST)	Peptide	SSTR 1-5	Metabotropic
NO	Gas	1 receptor	Metabotropic	Increase cyclic GMP
CO	Gas	1 receptor	Metabotropic	Increase cyclic GMP