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Intrinsic synaptic modulation in vertebrate brains: Depression - - PowerPoint PPT Presentation
Intrinsic synaptic modulation in vertebrate brains: Depression - - PowerPoint PPT Presentation
Intrinsic synaptic modulation in vertebrate brains: Depression Facilitation Mixed Dietmann et al 2000 Sites of Possible Change for Plasticity Facilitation: Minis same size, increase in frequency Residual Ca hypothesis for facilitation:
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Residual Ca hypothesis for facilitation: Presynaptic Ca builds up with each AP Facilitation: Minis same size, increase in frequency
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Sequestration of calcium after an action potential
Calcium binding proteins Na: Ca Exchange
Calcium ATPase Pump
Uptake into mitochondria and E.R.
Takes 100-500 msec to bring calcium levels to normal after an A.P.
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AP brings in 5 units of Ca 54 = 525 80% uptake before Next AP 1 unit left= 14 = 1 Next AP = 1 + 5 units 64 = 1296 (twice as much NT release!)
Ca4
Non-linear dependence of transmitter release on [Ca]i
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BUT: 1) Realistic simulations of expected peak and residual Ca2+ levels not able to account for facilitation. 2) Using Ca2+ sensitive dyes, pre- synaptic [Ca2+ ] does not account for enhanced synaptic transmission. 3) The time course of IK(Ca) is too fast. The decay of this current should reflect the decay of residual Ca2+.
Facilitation
Ca++ may be acting at multiple sites of the synaptic machinery
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PTP PTP: 1) Correlates with decay of Ca2+ image in whole terminal, not just at release sites;reduced by Ca2+ chelators. 2) In crustacean motor neurons, Na+ has a role. Entry of Na+ during AP firing may reduce the efficiency of the Na/Ca exchanger to get rid of Ca2+. 3) Ca2 + unloading from mitochrondria. 3) In Aplysia- MEPP frequency up with PTP, but not amplitude. Both pre- and post- synaptic Ca2+ chelators and postsynaptic hyperpolarization reduce PTP.
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Intrinsic synaptic modulation:
- Depression
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Shibere, a temperature sensitive fly mutant, vesicle recycling is blocked
Depression correlates with depleted vesicles
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Other mechanisms for depression: 1) Inactivation of ICa during repetitive activity 2) Activation of inhibitory currents (IKCa and IClCa 3) Transmitter release controlled by autoreceptors GABA responses are blocked by antagonists
- f presynaptic GABAa receptors.
4) Desensitization of post-synaptic receptors.
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Overlapping Stages of Intrinsic Plasticity
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Neuromodulatory control of synaptic strength Neuromodulation: Changing a neuron’s electrical properties through intracellular biochemical pathways initiated by neuroactive chemicals. Not usually rapid, not point to point, not simple excitation or inhibition
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Neuromodulation: Extrinsic Synaptic Modulation Control
Sites of Synaptic Change?
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Neuromodulation enhancing transmitter release through AP broadening
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Transmitter release can be also strengthened without increased Ca entry
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Modulators can have direct action on synaptic machinery. They can also affect other currents which control synaptic transmission: IK(Ca), ICl(Ca) Also possible post-synaptic actions
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Brain neuromodulatory pathways
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Brain neuromodulatory pathways- Serotonin imbalance
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Functions of electrical coupling: Fast Reliable Organize synchronous neuronal activity, Pass metabolites, second messengers, Ca2+ waves, Glial function Myelin organization.
Electrical Synaptic Transmission
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Electrical synaptic transmission
Dyes can pass between electrically coupled neurons
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Elektrische Synapse (leech neurons)
Electrical synaptic potential Electrical synaptic potential
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Electrical synapse (gap junction)
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