Cognitive Science 320
Spring 2011

Synapses and Synaptic Transmission: 

• changing permeability of the membrane to different ions
• equilibrium potentials of different ions
• passive, electrotonic spread of subthreshold currents
• mechanisms that are responsible for production of action potentials
• Soooo, everything you have learned so far is absolutely necessary for understanding synaptic processes.

• Images of synapses

• Details of chemical synapses and their neurotransmitters
  • Involves
    • changing permeabilities of membrane to different ions
    • equilibrium potentials of different ions
    • electrotonic (passive) current spread
    • mechanisms responsible for production of the presynaptic action potential
    • Presynaptic events -> diffusion through the synaptic cleft -> postsynaptic events
  • presynaptic mechanisms  synapse animation
    • regulation of release of neurotransmitter
    • The sequence of events:
      • action potential comes into the axon terminal (voltage-gated Na⁺ channels and voltage-gated K⁺ channels are activated), depolarizing the presynaptic axon
      • depolarization caused by the action potential activates voltage-gated Ca⁺² channels
      • Ca⁺² moves into the presynaptic axon terminal through the voltage-gated Ca⁺² channels, further depolarizing the axon terminal.
      • Ca⁺² activates a series of biochemical reactions which end in the release of the contents of the synaptic vesicle from the presynaptic axon into the synaptic cleft.
    • The vesicle is somehow pushed to the 'active zone' and the vesicle membrane fuses with the cell membrane of the presynaptic cell.
      • the activation of the vesicle and fusion with the membrane require many biochemical reactions between molecules used to mobilize the vesicle from the cytoskeleton AND biochemical reactions between molecules which facilitate fusion of the vesicle membrane and cell membrane of the presynaptic cell. (See Figure 2.30 and 2.32 on pages 48 and 50)
      •  presynaptic mechanisms
    • recycling of vesicle membrane occurs
      • this allows maintenance of the axon terminal's surface area
      • this recycles vesicle membrane, so the cell does not have to make new vesicles each time transmitter is released.
    • Removal of transmitter from the synaptic cleft
      • is necessary to decrease the length of time that the neurotransmitter can interact with the postsynaptic receptors
      • occurs through one of two main mechanisms
        • (1) reuptake of the intact neurotransmitter by the presynaptic axon terminals
          • Examples:  At the synapses that use the following  neurotransmitters there are reuptake molecules (membrane proteins) in the membrane of the presynaptic cell, which quickly and efficiently remove the neurotransmitter from the synaptic cleft and bring it into the presynaptic cell.
          • Examples of neurotransmitters that use reuptake mechanisms
            • norepinephrine (SNRIs block both norepinephrine reuptake and serotonin reuptake)
              • are used as anti-depressants to increase elevation in mood
              • amphetamines affect dopamine and norepinephrine
            • serotonin (SSRIs block uptake of serotonin: Prozac, Paxil, Celexa)
              • are used as anti-depressants to increase elevation in mood
              • used to treat depression, anxiety and obsessive-compulsive disorder
            • dopamine
              • creates feelings of euphoria
              • reuptake blockers include: cocaine, methylphenidate, Wellbutrin
            • glutamate
              • NMDA receptors
              • three types of non-NMDA receptors
            • g-amino butyric acid (GABA)
              • creates sedative, muscle relaxant effects
              • Diazepam blocks reuptake of GABA
            • glycine
            • choline (after acetylcholine is broken down, choline is taken into the presynaptic nerve terminal for reuse
        • (2) enzymatic breakdown of the neurotransmitter by enzymes on the surface of the postsynaptic cell
          • Example:  At the neuromuscular junction acetylcholine (ACh) is broken down into acetate and choline by the enzyme acetylcholinesterase.  The choline is then taken up by the presynaptic nerve through transporter mechanisms.              ACh ----> acetate + choline (which is reused)
  • postsynaptic mechanisms (Figure of ionotropic and metabotropic receptors) (Your book illustrates this in Figure 2.29 with few details.)
    • (1) quick-acting ion channels
      • Produce a quick change in membrane potential when the neurotransmitter binds onto the receptor for the neurotransmitter.  The receptor contains an ion channel.  When the neurotransmitter binds to the receptor it activates the channel to open (in most cases it opens, but in some it can close when the neurotransmitter binds to it).
      • EPSPs (excitatory postsynaptic potentials)
        • push the cell to threshold for an action potential
        • usually involves allowing positively charged ions to enter the cell, e.g., Na⁺ or Ca⁺²
        • glutamate NMDA receptors
          • single channel recordings
        • nicotinic acetylcholine receptors, single channel recordings
      • IPSPs (inhibitory postsynaptic potentials)
        • keep the cell from achieving threshold for an action potential
        • involves adjusting the membrane potential to a level which will keep the cell from reaching threshold.
          • this can be done by activating transmitter receptors which increase the permeability to Cl^-.  The cell will then hyperpolarize.
          • this can be done by activating transmitter receptors which increase the permeability to K⁺.  The cell will then hyperpolarize.
          • this can be done by closing the pore of transmitter receptors, thus decreasing the permeability to Na⁺.  The cell hyperpolarizes because normally there is a very small leak to Na⁺.  When this is stopped the cell hyperpolarizes.
          • Think about this: some inhibitory postsynaptic potentials might depolarize the cell.  How could this be?
        • single channel recordings from GABA_A receptors showing the effect of pentobarbital on channel openings
        • single channel recordings from glycine receptors
      • A look at measurement of ion flow through neurotransmitter-activated single channels
        • patch clamp technique
        • single channels activated by glutamate, acetylcholine, glycine,
      • Two types of presynaptic voltage-gated Ca²⁺ channels -  calcium
    • (2) sustained acting channels
      • G-protein coupled receptors (from Bear, Connors, Paradiso, p 115)
        • neurotransmitter molecules bind to receptor proteins
        • receptor proteins activate small proteins, called G-proteins, which are free to move along the intracellular face of the postsynaptic membrane.
        • the activated G-Proteins activate 'effector' proteins.
        • See G-protein interactions and intracellular signaling handout.
      • these may alter proteins (enzymes)
      • these may alter permeability of other ion channels
      • these may alter gene expression
      • amplification of the initial signal: neurotransmitter into activation of multiple intracellular molecules and pathways
      • cAMP pathways in the cell
    • Review of presynaptic and postsynaptic mechanisms
    • Neurotransmitter systems in the brain (Figure 2.34)
• Details of electrical synapses (animation)
  • characteristics  
    • there is no synaptic cleft
    • the cytoplasm is continuous through closable pores
      • pores consist of membrane proteins that form a connexon
      • gap junctions (connexin molecules)
      • six connexin molecules form a hemi-channel (a connexon)
    • the principles of electrotonic current flow are what cause current (information) to pass from cell to cell.  This depends on the length constant of the cells. 
    • they are faster than chemical synapses
  • mechanisms of action
    • electrical synapses are used primarily to send depolarizing signals
    • they are used to synchronize a group of cells
    • they can close or open in response to cellular conditions
      • increased intracellular Ca⁺² can decrease current through the synapse
      • decreased pH in the cell can decrease current through the synapse
      • addition or removal of a phosphate group can also influence current flow through the pore
    • molecules less than 1000 daltons can pass through the open pore from cell to cell (1 dalton = the weight of a hydrogen atom)
  • Advantages of electrical synapses
    • they are faster than chemical synapses
      • there is no synaptic delay associated with release of neurotransmitter
    • they allow synchronization of many cells quickly
    • can transmit other cellular signals (such as chemicals) to influence the connected cells
  • Disadvantages of electrical synapses COMPARED to chemical synapses
    • a small presynaptic axon terminal cannot activate a large postsynaptic cell
    • there cannot be amplification of the synaptic signal
    • a presynaptic action potential cannot be converted into an inhibitory postsynaptic potential (IPSP).
    • cannot be modified or modulated to the same extent that transmitter release from chemical synapses can be regulated.
  • Example of electrical synapses in Aplysia.
  •  
• Synaptic integration
  • EPSPs (excitatory postsynaptic potentials)
    • push the cell to threshold for an action potential
  • IPSPs (inhibitory postsynaptic potentials)
    • keep the cell from achieving threshold for an action potential
  • EPSPs and IPSPs sum within the dendrites and cell body.
  • usually there are no voltage-gated membrane proteins in the membranes of the dendrites and cell body.
  • The axon hillock (action potential generating site), is usually located where the axon exits the cell body of the neuron.  The electrical signal (sum of EPSPs and IPSPs) needs to be above threshold when it reaches the axon hillock for the cell to fire an action potential.
  • The closer the synapse is to the axon hillock, the stronger the current from its EPSP or IPSP will be, and the more effect it will have on whether an action potential is produced or not.
  • Spatial summation:  Spatial summation of EPSPs: when two or more presynaptic inputs are active at the same time, their individual EPSPs add together.
  • Temporal summation:  Temporal summation of EPSPs: when the same presynaptic fiber fires action potentials in quick succession, the individual EPSPs add together.
  • Timing of synaptic inputs to the postsynaptic cell as well as the spatial location of synapses are therefore of critical importance in synaptic integration.
  • Crab stomach pattern generator
  • Swimming pattern generator

Information on Glutamate receptors