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NESC 2570 (6)
Lecture

April 5th 2012.docx

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Department
Neuroscience
Course
NESC 2570
Professor
Stefan Kreuger
Semester
Winter

Description
April 5th 2012 April-05-12 11:38 AM Changes in calcium levels  Synapses in the mammilian brain can be switched in their strength o Partially dependent on the postsynaptic calcium levels in dendritic spines  Very small elevations have no effect  Modest elevations switch on a synaptic depression mechanism o Activation of calcium activated phosphatases, remove AMPA receptors  High elevations switch on calcium activated protein kinases, increasing the number of AMPA receptors found, and facilitate the firing of these synapses Changes in the number of transmitter receptors in the postsynaptic membrane may make a difference if all the receptors were saturated with their transmitter.  If they all were not, then changes in the number of receptors present may not have an effect on the synapse strength Several labs have tried to isolate the actions of a single axon using optical recording  Involve the use of fluorescent probes  There are a number of probes that change their fluorescence intensity or colour depending on whether or not they have bound the molecule of interest (such as calcium)  You can inject the calcium sensor into the cell, record electrically, and watch the calcium flashes under a microscope  They place a pinhole in the image plane that is exactly aligned with the area of interest, allowing only the light from the exact place of interest to pass through, allowing for a much sharper image (LSCM)  Advantage of optical recording is that it allows you to view what is occurring at only one synapse at a time, electrical recording only allows you to record the combined synapses from several axons at once (depending on which ones connect to each other) One theory of a way to make a synapse stronger is to increase the probability of release in response to a stimulus Textbook theory is that you should be trying to change the potency of the synapse  Increasing the number of receptors on the post synaptic cell (increasing AMPA receptors)  There are experiments that long term potentiation corresponds with increased release probability  So the postsynaptic changes as described by the textbook are not the whole story The change in postsynaptic potency is zero according to the tests conducted by Fine (review all those slides), but the release probability has increased Silent synapses  Only have functional NMDA type receptors  No AMPA receptors  What had been observed already is that if you record from hippocampal areas early in development, you find a lot more of these than you do later in development  Some of these silent synapses can be unsilenced however by inducing LTP Measuring release probability before and after LTP to unsilence  Before, the points are very close to the 45 degree line  But after LTP the release probabilities of the cell changes  This showed that immature synapses that are silenced express plasticity much like the textbook described  After LTP, the potency changes are insignificant, however the release probability changes have changed significantly Do persistent changes in synaptic strength require changes in synaptic morphology?  There is definitely an association shown between the two, but is it required?  We have never seen LTP under "our" experimental conditions, producing morphology changes  It's quite clear that spine formation aids in interaction with their presynaptic partners, however it is not required for potentiation to occur Patch pipette when attached can wash away the diffusible molecules from the cytoplasm where it is attached Experiment  When they recorded the frequency and responses of various neurons in V1 of cats retinal input.  It occurred to David Hubel and Torstin Wiesel had the idea that do cats start out sending signals at this level, or is this something then learn after birth  Addressed th
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