The Synapse Lecture 2

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jadnebalasca
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283133
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The Synapse Lecture 2
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2014-09-15 22:18:27
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Synapse
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Neuroscience Fall 14
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  1. Synaptic Neurons
    • Presynaptic neuron - neuron transmitting the neural signal (aka first neuron)
    • Postsynaptic neuron - neuron receiving the neural signal
  2. Two kinds of synapses
    • Electrical synapses
    • Chemical synapses
  3. Electrical synapses
    • Occurs at gap junctions that are 3nm apart
    • At this gap, connexin proteins make up connexons which when combined to another connexon forms a gap junction channel
    • Fast and fail safe transmission: synaptic delay of 0.2ms while chemical synaptic delay is 2ms
    • Do not involve neurotransmitters, thus cannot be modified like electrical synapses
    • Used when reactions of local neurons must be  highly synchronized
    • Gap junction channel - allows ions to pass from one cytoplasm to another
    • Electrically coupled - cells that pass through this channel causes a small amount of ionic current to flow across channels (PSP)
  4. Dense core vesicles (LDCV)
    Dense core vesicles (LDCV) - larger secretory vesicles containing dark protein granules that stimulate growth, facilitate neurotransmitters, and etc.
  5. Membrane differentiations
    dense accumulations of proteins at presynaptic membranes
  6. Active zones
    Where neurotransmitters are released
  7. Postsynaptic densities
    accumulations of proteins in the postsynaptic membrane that are sites of neurotransmitter receptors
  8. Chemical synapses
    • Most synapses in humans are chemical
    • Specialized for release and reception in chemical neurotransmitters
    • Converts electrical synapses from the axon to chemical synapses aka neurotransmitters which are stored in axon buoton terminal
  9. Post synaptic potentials
    Generally small electrical synapse but many neurons making contact can generate a strong potential
  10. CNS Synapses
    • Axodendritic - Axon to dendrite
    • Axosomatic - Axon to cell body 
    • Axoaxonic - Axon to axon
    • Gray's type 1: dissimilar cell differentiations (asymmetrical)
    • Gray's type 2: similar cell differentiations (symmetrical)
    • *similarity is based on differentiation thickness
  11. Neuromuscular Junction
    • Chemical synapses between lower and motor neuron axons and skeletal muscles
    • Largest synapses in the body 
    • Has large number of active zones and receptor folds
    • Active zones matched up to folds on motor end plate
    • Muscle receives sodium ions and causes them to contract
    • ACh is released from the presynaptic membrane when calcium channels open
    • ACh stimulates muscle sodium channels to open which then effect muscular contractions
  12. Three chemical families of Neurotransmitters
    • Amino acids (small and released from synaptic vesicles)
    • Amines (small and released from synaptic vesicles)
    • Peptides (larger and are released from secretory granules)
  13. Characteristics of a Neurotransmitter
    • Molecule must be synthesized and stored in neuron
    • Molecule must be released by the presynaptic axon when stimulated
    • Molecule must produce the desired response on the postsynaptic cell that the neurotransmitter should should
  14. Neurotransmitters in brain vs. muscles
    • Brain - fast transmission that utilizes amino acids (ex. GABA, Glutamite, Glycine)
    • Muscle - fast transmission that utilizes amines (acetylcholine)
  15. Neurotransmitters release
    • When voltage gated calcium channels open in the active zones
    • Calcium channels are activated through Na and K ion channels
    • When Ca gated channels open, levels rise signaling synaptic vesicles to open and release neurotransmitters to the synaptic cleft (exocytosis).
    • Endocytosis - vesicles are refilled with neurotransmitters
  16. Two main categories of neurotransmitter receptors
    (Instead of action potentials, which only occurs in axons, EPSP or IPSP occurs at the post-synaptic membrane)

    • Transmitter gated ion channels
    • -Fast acting system
    • -Membrane spanning proteins create a channel between the synapse and the cell. When transmitter binds to membrane, the channels open and ions pass through
    • -Excitatory Post Synaptic Potential (EPSP): If the ion channels receive Na, the cell depolarizes, bringing the membrane potential toward its threshold
    • -Inhibitory Post Synaptic Potential (IPSP): If the channels were permeable to CL, the membrane potential becomes more negative which has an inhibitory effect

    • G protein coupled receptors:
    • -Slower acting system
    • -Neurotransmitters bind to receptor proteins which activate small G effector proteins. These proteins activate enzymes that synthesize second messengers which trigger and regulate ion channels to affect membrane permeability.
  17. Neurotransmitter recovery
    • Neurotransmitters in the synaptic cleft must disappear for the neurons to prepare to fire again
    • Diffusion of particles help with the reuptake of the neurotransmitter via specialized transporter proteins
    • Enzymes in the synaptic cleft degrade the remaining neurotransmitters
  18. Synaptic integration
    process by which many synaptic potentials combine within one postsynaptic neuron
  19. EPSP summation
    • Spatial summation (additive):
    • -Adding the EPSPs generated simultaneously at different synapses on a dendrite
    • -More cells stimulating at the same time, adding these activity, the more excited it will be
    • Temporal summation (additive if time locked):
    • -Adding together EPSPs generated at the same time if they occur in rapid succession within 1-15ms
    • -Cells will retain charge and summate if generated within 1-15ms
  20. Dendritic contribution to synaptic integration
    Short and thick is ideal

    • Length of dendrite - internal resistance; the shorter it is the more able to maintain electrical charge
    • Width of the membrane - membrane resistance; thicker dendrite, harder electrical charge to escape
    • Excitable dendrites - some neuronal dendrites have active sodium, potassium, and calcium channels. Electrical potential can heighten neuronal transmission
  21. Inhibition of neural transmission
    Some synapses reduce the membrane potential which has an inhibitory influence on depolarization and neural transmission
  22. IPSPs
    • Bind to ertain neurotransmitters (like GABA) and are permeable to neural chloride
    • Chloride channels allow chloride to pass which brings potential closer to -65mv making it harder to depolarize
  23. Shunting
    • Inhibitory synapse located at the proximal end of a dendrite
    • This allows the ion to pass out of the cell due to the chemical gradient and affect the cell's voltage
    • The membrane potential is brought toward -65mv thus allowing release of the positive charged action potential to be released from the dendrite prior to reaching and exiting axon
  24. Identifying neurotransmitters
    • Immunocytochemistry: Injecting an animal with the neurotransmitter and creating antibodies, tagging the antibody, then applying the tagged antibodies to sampled brain tissue, seeing what they attach to
    • In situ hybridization: duplicating then constructing a nucleic acid strip and labeling it radioactively, then applying to brain tissue to see what it adheres to
  25. Neurotransmitters release
    • stimulate axonal cells and take sample of fluids
    • Assesses the biologic activity of the cells to determine if it mimics the activity of the synapse
    • If there is duplication of the expected action, chemically analyze the sample to assess its structure
  26. Receptor subtype
    When a neurotransmitter binds to a receptor. A receptor that accepts specific neurotransmitters is labelled as that "(neurotransmitter) receptor subtype"
  27. Other neurotransmitters
    • Catecholaminergic neurons:
    • -dopamine - regulates fine motor control
    • -norepinephrine - adrenaline
    • Serotonergic neurons:
    • -serotonin - emotional mood and behavior
    • Amino acidergic neurons:
    • -Glutamate (Glu) - excitatory
    • -Glycine (Gly) - inhibitory
    • -Gama aminobutyric acid (GABA) - inhibitory that regulates neurotransmission via excitatory and inhibitory actions
  28. ATP
    • Involved in catalyzing.
    • Key to energy and metabolism is possibly a neurotransmitter
  29. Endocannabinoids
    Released from postsynaptic membranes that provide communication back to presynaptic membrane. Retrograde messengers as a part of feedback system
  30. Myasthenia Gravis
    • Autoimmunie disorder
    • A person's autoimmune system creates antibodies that attack the ACh receptors located on muscles
    • ACh cannot lock onto the muscle receptors, thus a muscle function deteriorates
  31. G-protein coupled receptors and effectors
    • A Guanosine Triphosphate (GTP) binding protein is composed of three subunits (alpha, beta, gamma).
    • When at rest, the alpha subunit binds to the GDP.
    • As it collides with the proper receptor, GDP is released and exchanged for GTP from the cytosol
    • GTP bound alpha G-protein subunit splits, activating the G-protein
    • Beta Gamma subunit influence ion channels or Alpha subunit influence effector proteins which carry out their activity
    • GTP is eventually broken down and reverts back into GDP, the subunits re-combine and return to a resting state
    • G-proteins may also act on certain enzymes that create a series of biochemical reactions and alter neuronal function down the line via second messenger cascades

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