2017 Lectures
<p class="MsoNormal" >CASTILLO, Pablo, Presynaptic Plasticity,Einstein Med, March 23, 2017</p>
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Prof at Albert Einstein Col. of Medicine.
in the Dominick Purpura Dept of Neurosci.</p>
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Intro by Lu Chen (she was also a post-doc in the Nicholl Lab at UCSF.)</p>
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He is from Uruguay.</p>
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also used to work in the Rob Malenka Lab.</p>
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slide one:</p>
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relative contribution of glutamate vs GABA and both are dynamically regulated.</p>
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synaptic excit => EPSP (via glutamate)</p>
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and synap inhbi via GABA to IPSP.</p>
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trisynaptic loop of the HC.</p>
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perforant pathway to CA3 to CA1 etc.</p>
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and LTP and LTD seen in hc.</p>
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LONG TERM CHANGES AS A RESULTS OF SAY HIGH FREQ STIM</p>
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THAT LEADS TO INCR IN # OF RECEPTORS AT POST-SYNAP CITE:</p>
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ampa/ka-r</p>
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but also presynap forms of plasticity.</p>
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see his rev. in 2012 Cold Spring Harbor.</p>
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Homosynap plasticity (one syanpse) but also
heterosynap plasticity
with retrograde messengers...
(which goes to a neighboring presynap bouton)</p>
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story one: mech for presynap LTD at inhibitory synapses:</p>
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this is in rodent HC = hippocampus;</p>
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block IPSC with picrotoxin.</p>
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we found long-term inhib LTD...</p>
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he shows a heterosyanp inhib... influence.</p>
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I-LTD long-lasting disinhibtion</p>
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it changes the E/I blanace</p>
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and metaplasticity.</p>
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this is occurs all ove rthe brain...</p>
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HC = hipposampus...DSI = depolarization-induced suppression of inhibition</p>
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can get massive suppression of inhibition even with 5 sec of stim</p>
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this is in endocannabinoids... (uses a retrograde messenger)
discovered by Kano 2001 and Nicoll in 2001.</p>
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activ by CB! receptor...</p>
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uses 2-AG as retro msgr.</p>
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long lasting suppression of xmtr releases.</p>
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prediction 1:
apply CB1R antagonist...</p>
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can measure 2AG for a few minutes after stim.</p>
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prediction 2
mult episodes of DSI by prolonging... can induce I-LTD.</p>
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so, what accoutns for th elong-lasting reduciton in GABA release?</p>
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is protein synth requed for eCB-mediated iLTD</p>
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eCB = endocannabinoid.</p>
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genl accepted that local denr protein synth occurs in mammalina CNS.</p>
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is local protein synthesis involved in the presynap compartment.</p>
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we used aniomycin and cyclohexamide to block protein syntesis...</p>
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so, does CB1 activatio induce protein synthesis?</p>
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yes...</p>
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researcher (Ms Monday)
used FUNCAT... fluor method.</p>
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how do CB1 receptors talk to protein translation?</p>
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studies thi susing WIN...</p>
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we studied this using m7GpppG(M7)</p>
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it is an RNA cap analog...</p>
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Tommy Younts...</p>
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load soma with M7 and record from soma and from synaptic cells</p>
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Yes, presynaptic syntehsis is required for iLTD to occur in presynap terminals.</p>
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so, is there evidenc for translation machinery in CB1-containing presynap terminals?</p>
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(the dogma. NO protein synthesis in mature synapses)</p>
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Hungarians: Katona and Dudok...</p>
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they used STORM to see this... (20 to 50 nm spatial res)</p>
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can you find mRNA in presynap terminal...</p>
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yes... ribosomes are presen in the CB1 expressing presyanp terminals...</p>
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they find 5.8S rRNA using STORM in CB1R presyanp terminals.</p>
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conclusions 1:</p>
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fist direct demo for a role of presynap local translatio in LT plasticity in adult mammalina brain...</p>
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presynap syn proteins act as a lolecular switch to perisstenly reduce neuroxmtr relase</p>
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local translation can impart axons with compuational autonomy to rapidly respond to the environment, independen of the soma...</p>
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</p>
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2nd story:</p>
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novel form of presynap plasticiity an excitatory associative circuit in the HC.</p>
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lamellar organiz of HC.</p>
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shows JOhn Lisman diagram (from Neuron in 1999)</p>
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shows pattern separation vs pattern completion...</p>
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his work centers onf output of mossy cells and their connex to granule cells.</p>
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Loretne de No in 1934... first classed CA1, CA2 etc.</p>
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v detailed anatomy.</p>
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thorny excescences... later called Mossy cells (called that by Amarel)</p>
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a single MC = mossy cell can conact up to 30K GCs and abt 300 granule cells converge onto a single MC.</p>
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Mossy cell function... many theories.. eg</p>
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learning and memory etc.</p>
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3 new papers in Feb 2017 in Neuron last month...</p>
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so what kind of activity-dep plasticity, if any, is expressed by MC to GC synapses?</p>
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3 inputs to granulae cell (mossy cell fibers... close to the soma of the GC) vs latral perforant pathway is v distal)</p>
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we studied these in vitro...</p>
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work of Hashimotodani... massive LTP...</p>
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this MC to GC LTP is likely presysnaptic..</p>
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he highlights the + findings...</p>
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inner molecualr layer in rat dentate gyrus...</p>
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v high BDNF...</p>
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yes... it seems MC-DG LTP requries postsynap BDNF-TrkB signaling.</p>
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yes... we puffed in BDNF.</p>
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and PKA is involved at presyanp LTP/LTD...</p>
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massive commisural connex btwn two HC.</p>
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we did optogenetic activaiton of mossy cell fibers... shine laser on commisure.</p>
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yes... activating mossy cells can activate plasticity.</p>
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conclusion to part 2...</p>
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seems that MC to GC syanpses express a novel NMDAR indep. form of LTP that requries both postsyna and presyanp mechanisms.</p>
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