Seite - 6 - in Advances in Neuroimmunology

BrainSci. 2016,6, 19 Histological studiesof theCNSofCCL2-tgandCXCL10-tgmiceare limited.However,CCL2-tg SJLmicehavebeenreportedtobe freeofneurological impairmentbefore6monthofage [34]. Routine histologicalanalysisof theCNSof theCXCL10miceshowednoapparentneuropathological changes relative to theCNSof thenon-tgmice [29]. 5. SynapticFunctionintheHippocampusfromIL-6,CCL2,andCXCL10TransgenicMice For all three transgenic lines, physiological studies to assess synaptic function have been carriedout at theSchaffer collateral toCA1pyramidalneuronsynapseof thehippocampususing asimilarprotocol that involvedextracellularfieldpotential recordings fromacutely isolatedslices of hippocampus (Figure 2). This approachhas been extensivelyused for physiological studies of hippocampalsynaptic function.Onepotential limitationto thisapproach is that thenormal levelof neuroimmunefactorscouldbealteredbytheslicepreparationandrecordingprocedures.However, sucheffectswouldpresumablyalsooccur in thenon-tgslicesandthusbecontrolledfor. Figure 2. Measurement of synaptic functionusing extracellular recordings in hippocampal slices. (LeftPanel)Simplifieddiagramshowingtheplacementofstimulatingandrecordingelectrodesand recorded responses inafieldpotential recordingof synaptic transmissionat theSchaffer collateral to CA1 pyramidal neuron synapse in a hippocampal slice. Synaptic transmission is initiated experimentallybyelectrical stimulationofSchaffercollaterals,axonsof theCA3pyramidalneurons of thehippocampus. Stimulationof theSchaffercollateralelicitsa fEPSPinthedendritic regionand, dependingon the strengthof the stimulation, aPS in the somatic region; (Rightpanel) Repetitive stimulationcanresult inachange in themagnitudeofsynaptic responses. (A)Repetitivestimulation witha40msintervalbetweenthefirstandsecondstimulationresulted inanenhancementof the fEPSP (2nd) evokedby the second stimulation relative to the fEPSP (1st) evokedby thefirst stimulation; (B)Repetitivestimulationwitha10msintervalbetweenthefirstandsecondstimulationresulted in anenhancement thePS(2nd)evokedbythesecondstimulationrelative to thePS(1st)evokedbythe first stimulation in this slice; (C)Highfrequencystimulation(HSF) inducesa long-termenhancement of the fEPSP.Thegraphshows themagnitudeof the fEPSPenhancement relative tobaseline levels beforehighfrequencystimulationwasapplied (at thearrow). The initial, largeenhancementof the fEPSPis referred toaspost-tetanicpotentiation (PTP).Thedelayed, stable increase in themagnitudeof the fEPSPis referredtoas long-termpotentiation(LTP).Representativerecordingsareshownabove thegraph. Synaptic transmission toCA1pyramidalneuronswaselicitedbyelectrical stimulationof the Schaffercollaterals. Bothbaselinesynaptic transmissionelicitedbysinglestimulationsandsynaptic plasticityelicitedbyrepetitivestimulationwerestudied. Theresponse tosynaptic transmissionwas measuredinthedendriticregionoftheCA1neuronsasafieldexcitatorypostsynapticpotential (fEPSP), whichreflects themembranedepolarizationproducedbysynaptic transmission inapopulationof CA1neurons (Figure2). Insomestudies, recordingswerealsomade in thesomatic regionof theCA1 6