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BrainSci. 2016,6, 19 5.2. SynapticPlasticity in IL-6 tg,CCL2-tgandCXCL-10 tgMice Synapticplasticity isachange inthemagnitudeofsynaptic responses that resultswhenasynapse is repetitivelystimulated. Synapticplasticity isconsideredtobeanimportantcellularmechanismof memoryandlearning[71]. Short-termand/or long-termsynapticplasticityat theSchaffercollateral to CA1pyramidalneuronsynapsehasbeenstudiedinoneormoreof the transgenic lines. Resultsare summarized inTable1. 5.2.1. Short-TermSynapticPlasticity Inthis formofsynapticplasticity, repetitiveactivationofasynapseatshort intervals (<1s)elicitsa transient increaseordecrease in themagnitudeof thesynaptic response. Short-termsynapticplasticity is experimentallydeterminedbyapplying repetitive stimulation to theSchaffer collateralsusinga paired-pulse (P-P)paradigm.Themagnitudeof theplasticity is indicatedbythepaired-pulseratio (PPR,magnitudeof the response to the 2nd stimulationdividedbymagnitudeof the response to the1st stimulation). At theSchaffer collateral toCA1pyramidalneuronsynapse thepaired-pulse protocol results inanenhancement the fEPSP(i.e., aPPRgreater than1,Figure2A).Thisenhancement is referredtoaspaired-pulse facilitation(PPF).PPFreflectsgreater transmitter releasewith the2nd stimulationduetoactionsof residueCa2+ontheprobablyof transmitter release in thepresynaptic terminalsof theSchaffercollaterals [72–74]. Therewasnodifference inPPFof the fEPSPbetweenthehippocampusfromIL-6 tgandnon-tg mice at either age studied (1–2and3–6monthsof age) [60]. Thehippocampus fromCCL2-tgand non-tgmicestudiedat2–3monthsofagealsoshowednodifference inPPFof the fEPSP[67]. In the 7–12monthsCCL2-tgSJLmice,PPFof the fEPSPwas increasedat the40mspaired-pulse intervalbut notat longer intervalscomparedto thehippocampusfromnon-tgmice, indicatingactivity-induced presynapticchanges that impactexcitatorysynaptic transmission ina limitedmanner [61]. Therewas nosignificantdifference in thePPFbetweentheCXCL10tgandnon-tghippocampusfrom5–6months oldmice [68]. Asecondformofshort-termplasticity inducedbysynapticactivationoccurs inthesomaticregion of theCA1neuronsandaffects thePSthat isgeneratedbythe fEPSP.Plasticityof thePScanresult ina PPRgreater thanone(less inhibition;Figure2B)or less thanone(more inhibition)dependingonthe relativecontributionofsomatic/dendriticexcitabilityandrecurrent inhibitionto thesomatic region. Therewasnodifference inPPRof thePSbetween thehippocampus fromIL-6 tgandnon-tgmice ateitheragestudied (1–2and3–5monthsofage) [60], orbetween thehippocampus fromCCL2-tg andnon-tgmiceat2–3monthsofage[67]. PPRof thePSin thehippocampusfrom7–12monthsold CCL2-tgSJLmicewasincreasedcomparedtothehippocampusfromnon-tgmice, indicatingdecreased inhibitory influences in thesoma/dendritic region[61]. Therewasnosignificantdifference inPPRof thePSbetweentheCXCL10tgandnon-tghippocampusfrom5–6monthsoldmice [68]. 5.2.2. Long-TermSynapticPlasticity Long-lastingchanges insynaptic transmissionarealsoobservedat theSchaffercollateral toCA1 pyramidalneuronsynapse. Thesechangescan involveanincrease in themagnitudeof thesynaptic response, referredtoas long-termpotentiation(LTP),oradecrease in themagnitudeof thesynaptic response, referred toas long-termdepression (LTD).LTP is experimentally inducedbybrief, high frequencystimulationof theSchaffercollaterals,whereasLTDis inducedexperimentallybyprolonged stimulationof theSchaffercollateralsat lowfrequency. LTPhasbeenstudiedinhippocampalslices fromtheIL-6 tg,CCL2-tg,CCL2-tgSJLandCXCL10-tgmice,butstudiesonLTDhavenotappeared. Highfrequencystimulation(HFS)of theSchaffercollaterals inducesan immediateanddramatic increase in theamplitudeof the fEPSP,afterwhichtheenhancementdeclinessomewhat toasteady, stable level reflectingLTP(Figure2C).The initial enhancement isashorter formofsynapticplasticity referred to as post-tetanic potentiation (PTP). PTP results from the impact ofHFSonpresynaptic 8