Seite - 7 - in Advances in Neuroimmunology

BrainSci. 2016,6, 19 pyramidalneurons,wherepopulation spikes (PS)were recorded (Figure2). ThePS reflects action potentialsoccurring in thesoma/dendritic regionthatweregeneratedbysynapticdepolarizations ina populationofCA1pyramidalneurons.Data fromhippocampalslices fromthetransgenicmicewere comparedtodata fromhippocampalslices fromtherespectivenon-tg littermatecontrols. Resultsare summarizedinTable1. Inadditionto thestudiesof IL-6 tgmicediscussedinthis review, twoother studiesof synaptic function in thehippocampushaveappeared,both in thedentate region [64,65]. Inaddition,onestudyonsynaptic function in thecerebellumhasappeared[66]. Table1.Genotypicdifferences insynaptic function in thehippocampus. Measurement IL-6 tgvs.Non-tg CCL2-tgvs. Non-tg CCL2-tgSJL vs.Non-tg CXCL10-tg vs.Non-tg Age(months) 1–2 3–6 2–3 7–12 5–6 Synaptic transmission -fEPSP Ò Ò noΔ Ó noΔ -PS Ò Ò Ò Ó noΔ P-Psynapticplasticity -fEPSP(PPF) noΔ noΔ noΔ Ò noΔ -PS (PPR) noΔ noΔ noΔ Ò noΔ Long-termsynapticplasticity -PTP Ó noΔ noΔ Ò noΔ -LTP noΔ noΔ noΔ noΔ noΔ Reference [60] [67] [61] [68] Ó=decrease,Ò=increase,noΔ=nodifference. 5.1. SynapticTransmission ThehippocampusfromtheIL-6 tgmicewasstudiedat twoages,youngmice1–2monthsofage andadultmice3–6monthsofage.Resultsweresimilar for the twoagegroupsandshowedthat the fEPSPwasenhancedinthehippocampusfromtheIL-6 tgmicecomparedto thehippocampusfrom non-tgmiceof the sameagegroup [60]. Asaconsequenceof theenhanced fEPSP, thePSwasalso enhancedin the IL-6 tghippocampus[60]. Therewasnodifference in the fEPSPmagnitudebetweenthehippocampusfromtheCCL2-tgand non-tgmiceat2–3monthsofage,whereas thePSwassignificantly larger in thehippocampusfrom theCCL2-tgmice [67]. Thus, thehippocampus fromboth the IL-6 tgandCCL2-tgmice showedan increase inthePS, indicativeof increasedexcitability.However the increasedPSinthehippocampus fromtheIL-6 tgmicecouldbeexplainedbyalarger fEPSP,but the increasedPSinthehippocampus fromtheCCL2-tgmicecouldnot. Thisdifference indicates thatalthoughthefunctionalconsequence at the level of the PSwas similar for the IL-6 tg andCCL2-tg hippocampus, different underlying mechanismswere involved. The increasedexcitability in theIL-6 tgmicecouldunderlie theenhanced sensitivitytoglutamatereceptoragonists-inducedseizureactivity[69]andenhancedalcoholwithdrawal hyperexcitability [70]observedintheIL-6 tgmicecomparedto thenon-tgmice. TheCCL2-tgmicedid notshowtheenhancedalcoholwithdrawalhyperexcitabilityobservedintheIL-6 tgmice [70]. Effects glutamatereceptoragonistonseizureactivityhasnotbeentested in theCCL2-tgmice. Incontrast to theCCL2-tgmicewhereonlythePSwasalteredandanenhancementwasobserved, in thehippocampusfromtheCCL2-tgSJLmiceat7–12monthsofage,both the fEPSPandPSshowed areduction inmagnitudecomparedtonon-tghippocampus[61]. ThisdifferencebetweenCCL2-tg andCCL2-tgSJLhippocampusmaybedueto theolderageor thehigher levelofCCL2expression in theCCL2-tgSJLhippocampus. Incontrast to the IL-6 tg,CCL2-tgandCCL2-tgSJLhippocampus, therewasnosignificantdifference in themagnitudeof the fEPSPorPSbetweentheCXCL10tgand non-tghippocampusfrom5–6monthsoldmice [68]. 7