• No results found

Early life experience : neuroendocrine adaptations to maternal absence

N/A
N/A
Protected

Academic year: 2021

Share "Early life experience : neuroendocrine adaptations to maternal absence"

Copied!
27
0
0

Bezig met laden.... (Bekijk nu de volledige tekst)

Hele tekst

(1)Early life experience : neuroendocrine adaptations to maternal absence Enthoven, L.. Citation Enthoven, L. (2007, October 4). Early life experience : neuroendocrine adaptations to maternal absence. Retrieved from https://hdl.handle.net/1887/12379 Version:. Corrected Publisher’s Version. License:. Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden. Downloaded from:. https://hdl.handle.net/1887/12379. Note: To cite this publication please use the final published version (if applicable)..

(2) 5IFQJUVJUBSZBESFOBMBYJTPGUIF $%NPVTFJOGBOUEFTFOTJUJTFT UPSFQFBUFENBUFSOBM TFQBSBUJPOT CVUSFNBJOT IJHIMZSFTQPOTJWFUPTUSFTT. $IBQUFS. -&OUIPWFO .40JU[M /,POJOH  .WBOEFS.BSL&3EF,MPFU.

(3)

(4) Chapter 2. "CTUSBDU 1SFWJPVTTUVEJFTIBWFTIPXOUIBUBTJOHMFFQJTPEFPGIPVSTTFQBSBUJPOGSPNUIFNPUIFSQSPEVDFT JO UIF NPVTF QVQ B QSPGPVOE IZQPUIBMBNJDQJUVJUBSZBESFOBM )1"  SFTQPOTF *O UIJT TUVEZ XFFYBNJOFEJO$%NJDFXIFUIFSSFQFBUFEEBJMZCPVUTPGIPVSTNBUFSOBMTFQBSBUJPOXPVME SFTVMUJOBQFSTJTUFOUFMFWBUJPOPGDPSUJDPTUFSPOF'PSUIJTQVSQPTFUIFFĒFDUPGSFQFBUFEIPVST TFQBSBUJPOTGSPNQPTUOBUBMEBZTUPXBTNFBTVSFEPOCBTBMBOETUSFTTJOEVDFEMFWFMTPG"$5) BOEDPSUJDPTUFSPOFBTXFMMBTPOUIFFYQSFTTJPOPG)1"NBSLFSTBOEDGPTN3/"JOUIFCSBJO $JSDVMBUJOHMFWFMTPGHMVDPTFBOEHISFMJOXFSFBMTPNFBTVSFE . ѮFEBUBTIPXUIBUUIFJOGBOUTJOJUJBMJNNFEJBUF)1"SFTQPOTFUPIPVSTTFQBSBUJPOXBT. FMJNJOBUFEXIFONBUFSOBMTFQBSBUJPOTBSFSFQFBUFEUIFOFYUUXPEBZT%FTQJUFUIFBCTFODFPGBO )1"SFTQPOTFUPSFQFBUFETFQBSBUJPOT UIFNBUFSOBMMZEFQSJWFENPVTFDPOUJOVFEUPSFTQPOEUP OPWFMUZFYQPTVSF*GUIFSFQFBUFENBUFSOBMTFQBSBUJPOTXFSFDPNCJOFEFBDIUJNFXJUIOPWFMUZ FYQPTVSFUIFSFTQPOTFPGDPSUJDPTUFSPOFTFDSFUJPOSFMBUJWFUP"$5)XBTFOIBODFEѮFTFFĒFDUTPG TFQBSBUJPOPOUIF)1"BYJTXFSFSFëFDUFECZDGPTN3/"FYQSFTTJPOJOUIFQBSBWFOUSJDVMBSOVDMFVT PGUIFIZQPUIBMBNVT 17/ CVUOPUJODPSUFYPSUIBMBNVTDGPTN3/"JOUIF17/TIPXFEB QSPGPVOESFTQPOTFUPBTJOHMFTFQBSBUJPOBOETVCTFRVFOUEFTFOTJUJTBUJPOUPSFQFBUFETFQBSBUJPOT  CVUSFNBJOFESFTQPOTJWFUPOPWFMUZFYQPTVSF#BTBMDJSDVMBUJOHMFWFMTPGDPSUJDPTUFSPOFBOE"$5) XFSFQFSTJTUFOUMZTVQQSFTTFEIPVSTBѫFSTFQBSBUJPO BOFĒFDUUIBUBMTPUSBOTJFOUMZPDDVSSFEGPS $3)N3/"JOUIF17/1JUVJUBSZ10.$N3/"BOEUIFHMVDPDPSUJDPJESFDFQUPS (3 N3/" FYQSFTTJPOJOIJQQPDBNQVTPSIZQPUIBMBNVTEJEOPUDIBOHF CVUUIFNJOFSBMPDPSUJDPJESFDFQUPS .3 N3/"FYQSFTTJPOJOUIFIJQQPDBNQBMEFOUBUFHZSVTTIPXFEBQSPHSFTTJWFJODSFBTFXJUI SFQFBUFETFQBSBUJPOT$JSDVMBUJOHHISFMJOJODSFBTFEBOEHMVDPTFMFWFMTEFDSFBTFEBѫFSUIFTJOHMF BTXFMMBTUIFUIJSETFQBSBUJPOBOEUIVTEJEOPUSFëFDUUIFEFTFOTJUJTBUJPOPGUIFDPSUJDPTUFSPOF SFTQPOTF . *O DPODMVTJPO  XIJMF UIF JOGBOUT JOJUJBM )1" BYJT SFTQPOTF UP SFQFBUFE NBUFSOBM BCTFODF. SFBEJMZ EFTFOTJUJTFT BOE B TUBUF PG IZQPDPSUJDJTN JT QSPEVDFE  UIF )1" BYJT SFNBJOT IJHIMZ SFTQPOTJWFUPNJMETUSFTTPST. *OUSPEVDUJPO %VSJOHFBSMZQPTUOBUBMMJGFSBUTBOENJDFIBWFBTUSFTTIZQPSFTQPOTJWFQFSJPE 4)31 QPTUOBUBM EBZ QOE JOSBUT<  >BOEQOEJONJDF<> ѮJTQFSJPEJTDIBSBDUFSJTFECZ TUBCMFBOEMPXDJSDVMBUJOHCBTBMMFWFMTPGDPSUJDPTUFSPOFBOENPTU NJME TUSFTTPSTUIBUUSJHHFSB QSPGPVOE"$5)BOEDPSUJDPTUFSPOFSFTQPOTFBUBEVMUIPPEEPTPPOMZXFBLMZEVSJOHUIF4)31 ѮFIZQPSFTQPOTJWFOFTTPGUIF)1"BYJTJTEVFUPUIFQSFTFODFPGUIFNPUIFS< > XIJDIDBO CFEFNPOTUSBUFECZTFQBSBUJPOPGQVQTGSPNNBUFSOBMDBSFGPSBQSPMPOHFEQFSJPEPGUJNF"ѫFS  GPSFYBNQMF BTJOHMFIPVSTNBUFSOBMEFQSJWBUJPO CBTBMMFWFMTPG"$5)BOEDPSUJDPTUFSPOFBSF JODSFBTFE.PSFPWFS UIFTFDSFUJPOPGQJUVJUBSZBESFOBMIPSNPOFTIBTOPXCFDPNFSFTQPOTJWFUP .

(5) $IBQUFS NJMETUSFTTPST SFTVMUJOHJOBGVSUIFSSJTFJOQMBTNB"$5)BOEDPSUJDPTUFSPOF<  >ѮFTF OFVSPFOEPDSJOFFĒFDUTJOSFTQPOTFUPNBUFSOBMTFQBSBUJPOBSFBMSFBEZEFUFDUBCMFBTFBSMZBTBѫFS IPVSTPGNBUFSOBMTFQBSBUJPO CVUTJHOJêDBOUMZHSFBUFSBUBOEIPVST<  > . &WFS TJODF BEWFSTF FBSMZ MJGF FWFOUT IBWF CFFO JEFOUJêFE BT B NBKPS SJTL GBDUPS GPS UIF. EFWFMPQNFOU PG EFQSFTTJPO BOE BOYJFUZ EJTPSEFST JO IVNBOT <    >  SPEFOUT TFQBSBUFE BT QVQT GSPN NBUFSOBM DBSF IBWF CFFO XJEFMZ VTFE BT MBCPSBUPSZ NPEFM UP TUVEZ UIF VOEFSMZJOH NFDIBOJTN< >*OQBSUJDVMBS UIFCSJFGEBJMZTFQBSBUJPOPGNPUIFSBOEQVQT BQSPDFEVSF DBMMFEIBOEMJOH XBTTIPXOUPSFTVMUJOBQFSTJTUFOUBUUFOVBUJPOPG)1"SFTQPOTJWFOFTTJOMBUFS MJGF  QSFTVNBCMZ UISPVHI B NFDIBOJTN JOWPMWJOH NBUFSOBM DBSF FĒFDUT PO NFUIZMBUJPO PG UIF HMVDPDPSUJDPJESFDFQUPS (3 JOUIFEFWFMPQJOHCSBJO< >*ODPOUSBTU SFQFBUFETFQBSBUJPOT GPS BQQSPYJNBUFMZ  IPVST BOE MPOHFS VTVBMMZ XFSF TIPXO UP QSPEVDF JODSFBTFE )1" BYJT SFTQPOTJWFOFTTBOECFIBWJPVSBMGFBSGVMOFTTJOBEVMUSBUT<    >BOENJDF<    > . ѮF NFDIBOJTN VOEFSMZJOH UIFTF MBTUJOH FĒFDUT PG QSPMPOHFE EBJMZ TFQBSBUJPOT JT TUJMM. QPPSMZ VOEFSTUPPE .BUFSOBM DBSF JT JNQPSUBOU  CVU DBOOPU CF UIF POMZ GBDUPS <  > %BJMZ BDUJWBUJPOPGUIF)1"BYJT BTJOEVDFECZSFQFBUFEBOEQSPMPOHFETFQBSBUJPOPGNPUIFSBOEQVQT  IBTJOEFFECFFODPOTJEFSFEBOBEEJUJPOBMGBDUPS CFDBVTFJUXJMMSFTVMUJOFYQPTVSFUPJODSFBTFE MFWFMTPGDPSUJDPTUFSPOF QBSUJDVMBSMZBѫ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ѫFSIPVSTPGNBUFSOBMTFQBSBUJPO<>ѮFSFGPSF XFVTFEIPVSTPGNBUFSOBM BCTFODFUPEFUFSNJOFUIFJNNFEJBUFFĒ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

(6) Chapter 2. .BUFSJBMTBOE.FUIPET "OJNBMT 0ĒTQSJOHPG$%NJDF PCUBJOFEGSPN$IBSMFT3JWFS ѮF/FUIFSMBOET XBTVTFE"ѫFSBIBCJUVBUJPO QFSJPEPGUXPXFFLT UISFFGFNBMFTXFSFNBUFEXJUIPOFNBMFJOUZQFQPMZDBSCPOBUFDBHFT  DN DPOUBJOJOHTBXEVTUCFEEJOHBOEUJTTVFGPPE 43." )PQF'BSNT ѮF/FUIFSMBOET BOE XBUFS DPOUBJOJOH)$M BEMJCJUVNMJHIUTPOGSPNUPIPVSTJOBUFNQFSBUVSF ± °$ BOEIVNJEJUZ ™ DPOUSPMMFESPPN1SFHOBOUGFNBMFTXFSFJOEJWJEVBMMZUSBOTGFSSFEUP DMFBOUZQFQPMZDBSCPOBUFDBHFTDPOUBJOJOHTBXEVTUCFEEJOHBOEUJTTVFUPQSPWJEFOFTUCVJMEJOH NBUFSJBMEVSJOHUIFMBTUXFFLPGHFTUBUJPO'FNBMFTXFSFDIFDLFEGPSMJUUFSTEBJMZCFUXFFO BOEIPVST*GMJUUFSTXFSFQSFTFOU UIFEBZPGCJSUIGPSUIBUMJUUFSXBTUIFOEFêOFEBTQPTUOBUBM EBZ QOE 0OUIFEBZBѫFSQBSUVSJUJPO QOE MJUUFSTXFSFDVMMFEUPFJHIUIFBMUIZQVQT GPVS NBMFTBOEGPVSGFNBMFT  . "OJNBM FYQFSJNFOUT XFSF BQQSPWFE CZ UIF -PDBM $PNNJUUFF GPS "OJNBM )FBMUI  &UIJDT. BOE3FTFBSDIPG-FJEFO6OJWFSTJUZBOEDBSSJFEPVUJOBDDPSEBODFXJUI&VSPQFBO$PNNVOJUJFT $PVODJM%JSFDUJWF&&$ѮFQSPUPDPMTXFSFBQQSPWFECZUIF"OJNBM$BSF$PNNJUUFFPG UIF'BDVMUZPG.FEJDJOF -FJEFO6OJWFSTJUZ -FJEFO ѮF/FUIFSMBOET  4FQBSBUJPOQSPDFEVSFT .PUIFSTOVSTJOHMJUUFSTTFMFDUFEGPSNBUFSOBMTFQBSBUJPOXFSFSFNPWFEGSPNUIFJSDBHFBOEQMBDFE JODMFBOUZQFQPMZDBSCPOBUFDBHFTBUIPVSTѮFIPNFDBHFDPOUBJOJOHUIFQVQTSFNBJOFE JOUIFBEKBDFOUSPPNPOBIFBUJOHQBE °$ UPDPOUSPMGPSQVQCPEZUFNQFSBUVSF"ѫFS IPVST BUIPVST UIFNPUIFSTXFSFSFVOJUFEXJUIUIFJSQVQTBOEMFѫVOEJTUVSCFEVOUJMUIF OFYUTFQBSBUJPOQFSJPEPSVOUJMUFTUJOH$POUSPMMJUUFSTXFSFMFѫVOEJTUVSCFE /PWFMUZFYQPTVSF 'PSOPWFMUZFYQPTVSFêSTUUIFNPUIFSXBTSFNPWFEGSPNUIFIPNFDBHFѮFO JOBOBEKBDFOU SPPN UIFQVQTXFSFJOEJWJEVBMMZQMBDFEJODMFBOOPWFMDBHFTUPJOEVDFOPWFMUZTUSFTTѮFTFOPWFM DBHFT XFSF QMBDFE PO IFBUJOH QBET   ž$  UP DPOUSPM GPS QVQ CPEZ UFNQFSBUVSF "ѫFS  NJOVUFT UIFQVQTXFSFFJUIFSQMBDFECBDLXJUIUIFJSNPUIFSTJOUIFIPNFDBHFPSTBDSJêDFE . *GOPWFMUZFYQPTVSFUPPLQMBDFPOBUFTUJOHEBZ GPVSQVQT UXPNBMFTBOEUXPGFNBMFT XFSF. TBDSJêDFEJNNFEJBUFMZBѫFSSFNPWBMPGUIFEBNGSPNUIFIPNFDBHFѮFSFNBJOJOHQVQTXFSF UIFOUSBOTGFSSFEUPOPWFMDBHFTBOETBDSJêDFENJOVUFTMBUFSGPSUFTUJOH"MMPUIFSQSPDFEVSFT SFNBJOFEDPOTUBOU &YQFSJNFOUBMEFTJHOT &YQFSJNFOU*5PJOWFTUJHBUFUIFJNNFEJBUF DVNVMBUJWFFĒFDUTPGSFQFBUFETFQBSBUJPOTNJDFXFSF TFQBSBUFEPODF QOE UXJDF QOETBOE PSUISFFUJNFT QOET BOE GSPNNBUFSOBMDBSF GPSBQFSJPEPGIPVST#FGPSF BUIPVST BTXFMMBTBUUIFFOEPGFBDITFQBSBUJPOTFTTJPO BU  IPVST  NJDF XFSF TBDSJêDFE GPS EFUFSNJOBUJPO PG QFSJQIFSBM BOE DFOUSBM NBSLFST PG .

(7) $IBQUFS UIF)1"BYJT"UQOEPOFHSPVQPGBOJNBMTTFSWFEBTCBTBMNFBTVSFNFOUGPSCPUIUIFOPO TFQBSBUFEBOEêSTUUJNFTFQBSBUFEBOJNBMT/POTFQBSBUFEBOJNBMTXFSFPOMZNFBTVSFEBU IPVST TJODFOPDJSDBEJBOFĒFDUTXFSFEFUFDUFEGPSDPSUJDPTUFSPOFJOi&YQFSJNFOU*uѮFêYFE GBDUPSTXFSF53&"5.&/5 OPOTFQBSBUFETFQBSBUFE CBTBM TFQBSBUFE

(8) IPVST. BOE"(& QOET BOE  . &YQFSJNFOU**5PUFTUXIFUIFSQVQTBUQOEFYIJCJUFEBOBEVMUMJLFSFTQPOTFUPUIFUIJSE. TFQBSBUJPO TFTTJPO  BU  IPVST NPUIFST XFSF SFNPWFE GSPN UIFJS OFTUT UP JOJUJBUF NBUFSOBM TFQBSBUJPOBOEUIFIPNFDBHFTDPOUBJOJOHUIFMJUUFSTXFSFQMBDFEPOBIFBUJOHQBEѮFSFBѫFS  FWFSZIPVSCMPPETBNQMFTXFSFUBLFOVQUPIPVSTPGNBUFSOBMBCTFODF'PSUIJTQVSQPTF UP NJOJNJTFOFTUFĒFDUT GSPNFBDIMJUUFSGPVSQVQT UXPNBMFTBOEUXPGFNBMFT XFSFTBDSJêDFE BUUXPEJĒFSFOUUJNFQPJOUT"UIPVST CBTBMUJNFQPJOU POFHSPVQPGBOJNBMTTFSWFEBTB CBTBMNFBTVSFNFOUGPSCPUIOPOTFQBSBUFEBOEêSTUUJNFTFQBSBUFEBOJNBMT'JYFEGBDUPSTXFSF 53&"5.&/5 OPOTFQBSBUFEBUQOETJOHMFTFQBSBUJPOBUQOEUSJQMFTFQBSBUJPOBUQOET  BOE UFTUFEBUQOE BOE5*.& CBTBM IPVST BOE      BOEIPVSTPGNBUFSOBM TFQBSBUJPO  . &YQFSJNFOU***5PEFUFSNJOFXIFUIFSUIFEFTFOTJUJTBUJPOUPNBUFSOBMTFQBSBUJPOPCTFSWFE. JOi&YQFSJNFOU*BOE**uXBTBOBHFTQFDJêDFĒFDUXFSFQFBUFEUIJTFYQFSJNFOU CVUUIJTUJNF JODMVEFE BO  IPVST NBUFSOBM TFQBSBUJPO BQQMJFE UP TFQBSBUF HSPVQT PG OBÐWF BOJNBMT BU QOET BOE0OUFTUEBZT GPVSQVQTGSPNFBDIMJUUFS UXPNBMFTBOEUXPGFNBMFT XFSFTBDSJêDFE JNNFEJBUFMZQSPWJEJOHBCBTBMTBNQMF BUIPVST ѮFPUIFSGPVSQVQTXFSFTBDSJêDFEBѫFS IPVSTPGNBUFSOBMTFQBSBUJPO BU ѮFêYFEGBDUPSTXFSF53&"5.&/5 TJOHMFTFQBSBUJPO BUQOET PSEPVCMFTFQBSBUJPOBUQOETBOE UFTUFEBUQOEUSJQMFTFQBSBUJPOTBUQOE  BOE UFTUFEBUQOE BOE5*.& CBTBMBOEIPVSTNBUFSOBMTFQBSBUJPO  . &YQFSJNFOU*7XBTEFTJHOFEUPUFTUXIFUIFSQVQTXFSFBCMFUPSFTQPOEUPOPWFMUZTUSFTTXJUI. JODSFBTFEDPSUJDPTUFSPOFBOE"$5)EJSFDUMZBѫFSBêSTU TFDPOEPSUIJSEQFSJPEPGTFQBSBUJPO 0OUFTUEBZTGPVSQVQTGSPNFBDIOFTU UXPNBMFTBOEUXPGFNBMFT XFSFTBDSJêDFEIPVSTBѫFS NBUFSOBMTFQBSBUJPO QSPWJEJOHBiTFQBSBUFEuTBNQMF BUIPVST ѮFSFNBJOJOHQVQTXFSF UIFOFYQPTFEUPOPWFMUZBOETBDSJêDFENJOVUFTMBUFS'JYFEGBDUPSTXFSF53&"5.&/5 OPO TFQBSBUFEBUQOETJOHMFTFQBSBUJPOBUQOEUSJQMFTFQBSBUJPOBUQOET BOE UFTUFEBUQOE  BOE5*.& CBTBM FJUIFSBUIPVSTPSBѫFSIPVSTPGNBUFSOBMTFQBSBUJPOBUIPVST NJOVUFTJOEJWJEVBMOPWFMUZFYQPTVSF  . &YQFSJNFOU7ѮFPCKFDUJWFTXFSF  UPEFUFSNJOFUIFSFTQPOTFPGDPSUJDPTUFSPOF HISFMJO. BOEHMVDPTFVOEFSUIFDPOEJUJPOTPGEFTFOTJUJTBUJPOUPSFQFBUFENBUFSOBMTFQBSBUJPOTBOE  UP EFUFSNJOFBDUJWBUJPOPGDFOUSBMIZQPUIBMBNJDCSBJOBSFBTJOSFTQPOTFUPNBUFSOBMTFQBSBUJPOBOE OPWFMUZCZNFBTVSJOHDGPTN3/"FYQSFTTJPO1VQTXFSFTBDSJêDFEBѫFSUIFêSTUPSUIFUIJSE QFSJPEPGIPVSTPGTFQBSBUJPOGSPNUIFEBNJOUIFBCTFODFPSQSFTFODFPGBEEJUJPOBMOPWFMUZ FYQPTVSF/POTFQBSBUFEBOJNBMTTBDSJêDFEBUUIFTFUJNFQPJOUTTFSWFEBTCBTBMDPOUSPMT1MBTNB DPSUJDPTUFSPOFMFWFMTXFSFEFUFSNJOFEJOBMMUIFTFHSPVQT#MPPEHMVDPTFBOEHISFMJOMFWFMTXFSF NFBTVSFEPOMZVOEFSCBTBMDPOEJUJPOTBOEBѫFSIPVSTPGNBUFSOBMBCTFODF'JYFEGBDUPSTXFSF .

(9) Chapter 2 UIFO53&"5.&/5 TJOHMFTFQBSBUJPOBUQOEBOEUSJQMFTFQBSBUJPOBUQOET BOE UFTUFE BU QOE   BOE 5*.& CBTBM BOE TFQBSBUFE  &YQSFTTJPO MFWFMT PG DGPT BOE $3) N3/" XFSF NFBTVSFEJOUIF17/BOEPG/1:N3/"JOUIFBSDVBUFOVDMFVTJOBMMUSFBUNFOUHSPVQT'JYFE GBDUPST TJNJMBSBTGPSDPSUJDPTUFSPOF XFSFUIFO53&"5.&/5 TU4&1BOESE4&1 BOE5*.& CBTBM TFQBSBUFE OPWFMUZ  $PMMFDUJPOPGCMPPEQMBTNBBOECSBJOT "UTQFDJêFEUJNFQPJOUTEFTDSJCFEJO&YQFSJNFOUT*UP*7 TFFi&YQFSJNFOUBMEFTJHOTu BOJNBMT XFSF TBDSJêDFE CZ EFDBQJUBUJPO BOE USVOL CMPPE XBT DPMMFDUFE JOEJWJEVBMMZ JO  NM &%5" DPBUFENJDSPDFOUSJGVHFUVCFT#MPPETBNQMFTXFSFLFQUPOJDFBOEDFOUSJGVHFEGPSNJOVUFTBU SQNBUž$1MBTNBXBTUIFOUSBOTGFSSFEUPNM&QQFOEPSGUVCFTBOETUPSFEGSP[FOBU ž$VOUJMEFUFSNJOBUJPOPGDPSUJDPTUFSPOFBOE"$5)DPODFOUSBUJPOT . #MPPE HMVDPTF MFWFMT XFSF NFBTVSFE "DDV$IFDL $PNQBDU  3PDIF  (FSNBOZ  VTJOH B. ESPQMFUPGUSVOLCMPPEMFѫPOUIFIFBEPSCPEZ"ѫFSEFDBQJUBUJPOXIPMFIFBET PGXIJDITLJO BOEKBXTXFSFSFNPWFE XFSFTOBQGSP[FOJOJTPQFOUBOFPOESZJDFBOETUPSFEBUž$GPSJOTJUV IZCSJEJTBUJPO )PSNPOFBOBMZTJT 1FS FYQFSJNFOU QMBTNB DPSUJDPTUFSPOF BOE "$5) DPODFOUSBUJPOT XFSF NFBTVSFE TFQBSBUFMZ VTJOH DPNNFSDJBMMZ BWBJMBCMF SBEJP JNNVOPBTTBZ 3*"  LJUT DPOUBJOJOH. . *PEJOF MBCFMMFE. DPSUJDPTUFSPOFPS"$5) SFTQFDUJWFMZ .1#JPNFEJDBMT*OD 64" $PSUJDPTUFSPOFDPODFOUSBUJPOT XFSFEFUFSNJOFEJOEVQMJDBUFGSPNBOFYUFOEFETUBOEBSEDVSWF         BOEOHDPSUJDPTUFSPOFNM TJODFXFOPUFEUIBUUIFMPXFSCPVOEBSZQSPWJEFECZUIFLJUXBT OPUTFOTJUJWFFOPVHIUPNFBTVSFCBTBMQMBTNBDPODFOUSBUJPOT"$5)TBNQMFTXFSFEFUFSNJOFE JOBEJMVUJPO TUBSUJOHXJUI•MCMPPEQMBTNB  . 1MBTNBMFWFMTPGHISFMJOXFSFNFBTVSFEVTJOHBDPNNFSDJBMMZBWBJMBCMF3*"LJUDPOUBJOJOH *PEJOFMBCFMMFEHISFMJO -JODP3FTFBSDI 64" (ISFMJODPODFOUSBUJPOTXFSFEFUFSNJOFEJOB. EJMVUJPO TUBSUJOHXJUI•MCMPPEQMBTNB7JBMTGPSFBDI3*"XFSFDPVOUFEGPSNJOVUFTJO BHBNNBTDJOUJMMBUJPODPVOUFS 1BDLBSE.JOBYJ(BNNBDPVOUFS 4FSJFT  *OTJUVIZCSJEJTBUJPO #SBJOTXFSFTFDUJPOFEBUž$JOBDSZPTUBUNJDSPUPNFBU•NJOUIFDPSPOBMQMBOFBUUIFMFWFM PGUIF17/ QJUVJUBSZBOEEPSTBMIJQQPDBNQVT4FDUJPOTXFSFUIBXNPVOUFEPOQPMZ-MZTJOF  DPBUFETMJEFT BJSESJFEBOELFQUBUž$ . *O TJUV IZCSJEJTBUJPOT XFSF QFSGPSNFE VTJOH 4VMQIVS MBCFMMFE SJCPOVDMFPUJEF QSPCFT GPS. DPSUJDPUSPQIJO SFMFBTJOH IPSNPOF $3) SBU GVMM MFOHUI DPEJOH SFHJPO NFBTVSFE JO 17/  HMVDPDPSUJDPJE SFDFQUPS (3 NPVTF FYPO  GSBHNFOU NFBTVSFE JO 17/  IJQQPDBNQVT BOE QJUVJUBSZ  NJOFSBMPDPSUJDPJE SFDFQUPS .3 NPVTF FYPO  SFHJPO NFBTVSFE JO IJQQPDBNQVT  BOE QSPPQJPNFMBOPDPSUJO 10.$ NPVTF  LC GSBHNFOU NFBTVSFE JO QJUVJUBSZ  4FDUJPOT XFSF êYFE JO  QBSBGPSNBMEFIZEF HMVUBSBMEFIZEF BOE UIFSFBѫFS BDFUZMBUFE JO  .

(10) $IBQUFS BDFUJDBOIZESJEFJO.USJFUIBOPMBNJOF)$M4VCTFRVFOUMZ CSBJOTFDUJPOTXFSFEFIZESBUFEJO JODSFBTJOHDPODFOUSBUJPOTPGFUIBOPM5JTTVFTFDUJPOT CSBJOTFDUJPOTQFSTMJEF XFSFTBUVSBUFE XJUIʍMPGIZCSJEJTBUJPOCVĒFS N.5SJT)$M Q) GPSNBNJEF N./B$M  N.&%5" Q) ¤%FJOIBSEUT ʍHNMZFBTUUSBOTGFS3/" ʍMNMUPUBM3/"  NHNM TBMNPO TQFSN %/"   EFYUSBO TVMGBUF   N. EJUIJPUISFJUPM   4%4 BOE  TPEJVN UIJPTVMGBUF  DPOUBJOJOH BQQSPYJNBUFMZ  Y  DQN 4VMQIVS MBCFMMFE SJCPOVDMFPUJEF QSPCF#SBJOTFDUJPOTXFSFDPWFSTMJQQFEBOEJODVCBUFEPWFSOJHIUBUž$ѮFGPMMPXJOHEBZUIF TFDUJPOTXFSFSJOTFEJO¤44$ USFBUFEXJUI3/"TF" NHNM BOEXBTIFEJOJODSFBTJOHMZ TUSJOHFOU44$TPMVUJPOTBUSPPNUFNQFSBUVSF'JOBMMZ TFDUJPOTXFSFXBTIFEJO¤44$GPS NJOVUFTBUž$BOEEFIZESBUFEUISPVHIJODSFBTJOHDPODFOUSBUJPOTPGFUIBOPM 'PSEFUFSNJOJOHDGPTN3/"FYQSFTTJPO 17/ JOTJUVIZCSJEJTBUJPOTVTJOH1IPTQIPSMBCFMMFE PMJHPOVDMFPUJEF QSPCFT XFSF QFSGPSNFE BT EFTDSJCFE QSFWJPVTMZ <> 4MJEFT XFSF PQQPTFE UP ,PEBL#JPNBY.3êMN &BTUNBO,PEBL$P 3PDIFTUFS /: BOEEFWFMPQFE . "VUPSBEJPHSBQITXFSFEJHJUJTFEBOESFMBUJWFMFWFMTPGN3/"FYQSFTTJPOXFSFEFUFSNJOFECZ. DPNQVUFSBTTJTUFEPQUJDBMEFOTJUPNFUSZ "OBMZ4*4 4Pѫ*NBHJOH4ZTUFN(NC) ѮFBWFSBHF EFOTJUZPGNFBTVSFNFOUTXBTUBLFOGPSFBDIBOJNBM 4UBUJTUJDBMBOBMZTJT *OFBDIFYQFSJNFOUFWFSZUSFBUNFOUDPOTJTUFEPGUISFFMJUUFSTQFSBHFHSPVQ O %BUBXFSF BOBMZTFE CZ BOBMZTJT PG WBSJBODF "/07"  ѮF MFWFM PG TJHOJêDBODF XBT TFU BU 1 8IFO BQQSPQSJBUF UIJT XBT GPMMPXFE CZ 5VLFZT QPTU IPD DPNQBSJTPOT ѮF JOJUJBM BOBMZTFT JO FBDI FYQFSJNFOUJODMVEFETFYBTBGBDUPS CVUCFDBVTFJUXBTOPUBTJHOJêDBOUGBDUPSJOBOZFYQFSJNFOU  EBUBXFSFDPMMBQTFEBDSPTTUIJTWBSJBCMF%BUBBSFQSFTFOUFEBTNFBO±4&.. 3FTVMUT *O&YQFSJNFOU*UIFJNNFEJBUF DVNVMBUJWF FĒFDUTXFSFJOWFTUJHBUFEPGPOF QOE UXP QOETBOE PSUISFF QOET BOE UJNFTIPVSTEBJMZNBUFSOBMTFQBSBUJPO T POUIFCBTBM EFWFMPQNFOUPGCPUIDFOUSBMBOEQFSJQIFSBM)1"BYJTNBSLFST $PSUJDPTUFSPOF 'JHVSF". 8FPCTFSWFEBNBJOBĒFDUPGUSFBUNFOU '   1 BOEBOJOUFSBDUJPOCFUXFFOBHFBOE USFBUNFOU '   1 JOEJDBUJOHUIBUUIFFĒFDUPGBEEJUJPOBMTFQBSBUJPOT USFBUNFOU  EFQFOEFEPOUIFQSFWJPVTEBJMZFYQFSJFODFTPGUIFBOJNBMTѮFêSTUQFSJPEPGTFQBSBUJPOBUQOE SFTVMUFEJOBSPCVTUJODSFBTFJODPSUJDPTUFSPOF 1 "ѫFSUIFTFDPOE QOE BOEUIJSE QOE  QFSJPEPGTFQBSBUJPOUIJTDPSUJDPTUFSPOFJODSFBTFXBTDPNQMFUFMZBCPMJTIFE#BTBMDPSUJDPTUFSPOF UIFOFYUNPSOJOHIPVSTBѫFSFBDIDPOTFDVUJWFTFQBSBUJPO BUQOETBOE XBTTJHOJêDBOUMZ MPXFSDPNQBSFEUPOPOTFQBSBUFEBOJNBMT 1  .

(11) Chapter 2 A. B. 'JHVSF /POTFQBSBUFE /4&1 CBTBMBOENBUFSOBMTFQBSBUJPOJOEVDFEQMBTNBDPSUJDPTUFSPOF " BOE"$5) # MFWFMTJO NPVTFQVQTUFTUFEBUEJĒFSFOUBHFT OPOTFQBSBUFEBUIPVSTCBTBMCBTBMMFWFMTBUIPVSTPGQVQTNBUFSOBMMZ TFQBSBUFE GPS  IPVST PO UIF QSFDFEJOH EBZ T  TFQBSBUFE TFQBSBUJPO JOEVDFE MFWFMT BU  IPVST PG BOJNBMT TFQBSBUFEGPSIPVST .BUFSOBMTFQBSBUJPOUPPLQMBDFBUQOET BOESFTVMUJOHJONJDFUIBUXFSFTFQBSBUFEGPS UIFêSTUUJNFBUQOE GPSBTFDPOEUJNFBUQOE BOEGPSBUIJSEUJNFBUQOEѮFDPOUSPMHSPVQBUQOEBMTP TFSWFTBTBACBTBMHSPVQGPSNBUFSOBMTFQBSBUJPOBUUIJTBHF%BUBSFQSFTFOUNFBO™4&. *1 TJHOJêDBOU GSPNiOPOTFQBSBUFEuBUUIFTBNFEBZ #1 TJHOJêDBOUGSPNiCBTBMu . "$5) 'JHVSF#. 8FPCTFSWFEBNBJOFĒFDUPGUSFBUNFOU '  1 ѮFêSTUQFSJPEPGTFQBSBUJPOBU QOESFTVMUFEJOBSPCVTUJODSFBTFJO"$5) 1 "ѫFSUIFTFDPOEQFSJPEPGTFQBSBUJPOBU QOE"$5)XBTJODSFBTFEDPNQBSFEUPCPUICBTBMMFWFMT 1 BOEOPOTFQBSBUFEBOJNBMT 1 BMUIPVHIUIFSFTQPOTFXBTMFTTUIBOBUQOEѮFUIJSEQFSJPEPGTFQBSBUJPO QOE EJE OPUEJĒFSGSPNOPOTFQBSBUFEBOJNBMTѮFNBHOJUVEFPGUIFSFTQPOTFXBTTNBMMFSUIBOBѫFS BêSTU QOE PSTFDPOE QOE QFSJPEPGTFQBSBUJPODPNQBSFEUPCBTBM"$5)#BTBM"$5) XBTTJHOJêDBOUMZMPXFSBѫFSFBDIDPOTFDVUJWFQFSJPEPGTFQBSBUJPODPNQBSFEUPOPOTFQBSBUFE BOJNBMT BUQOETBOE1  $3)N3/"JO17/ 5BCMF. $3)N3/"FYQSFTTJPOMFWFMTJODSFBTFEXJUIBHF '   1 "ѫFSUIFêSTUTFQBSBUJPO .

(12) $IBQUFS QFSJPEBUQOECBTBMMFWFMTPG$3)N3/"FYQSFTTJPOXFSFEFDSFBTFEDPNQBSFEUPOPOTFQBSBUFE BOJNBMT 1 CVUBѫFSBTFDPOEQFSJPEPGEFQSJWBUJPO QOE CBTBMQOE UIJTEJĒFSFODF XBTBCPMJTIFE 10.$N3/"JOQJUVJUBSZ 5BCMF. /FJUIFSCBTBM OPSTFQBSBUJPOJOEVDFEMFWFMTPG10.$N3/"FYQSFTTJPOJOUIFQJUVJUBSZXFSF BĒFDUFECZNBUFSOBMTFQBSBUJPO JSSFTQFDUJWFPGUIFOVNCFSPGSFQFUJUJWFTFQBSBUJPOT .3N3/"JOIJQQPDBNQVT 5BCMF. .3 N3/" FYQSFTTJPO XBT NFBTVSFE JO UIF $"  $"  $" BOE EFOUBUF HZSVT %(  IJQQPDBNQBMTVCêFMET8FEFUFDUFETVCêFMETQFDJêDFĒFDUTJOUIF$"BSFBNBUFSOBMTFQBSBUJPO EJEOPUBĒFDUFYQSFTTJPO OFJUIFSBѫFSIPVSTOPSBUCBTBMMFWFMT8FPCTFSWFEBNBJOFĒFDUPG BHFJOUIF$" '   1 BOE%( '   1 BOEBOJOUFSBDUJPOCFUXFFO 5BCMF&YQSFTTJPOPGN3/"GPSDFOUSBM)1"BYJTNBSLFSTJOTFMFDUFECSBJOSFHJPOT. CRH. PVN. NSEP basal separated POMC pituitary NSEP basal separated MR hippocampus CA1 NSEP basal separated hippocampus CA2 NSEP basal separated hippocampus CA3-4 NSEP basal separated hippocampus DG NSEP basal separated GR PVN NSEP basal separated pituitary NSEP basal separated hippocampus CA1 NSEP basal separated. pnd 3 35.34 ±2.72 34.00 ±3.29 46.16 ±1.75 44.81 ±1.51 39.99 ±2.09 41.46 ±3.49 95.01 ±4.10 103.02 ±2.15 58.21 ±3.24 58.59 ±1.43 57.35 ±2.95 65.42 ±2.00 37.73 ±2.13 37.10 ±2.13 59.65 ±1.83 57.83 ±1.06 38.42 ±2.49 40.05 ±1.85. pnd 4 40.57 ±2.59 31.92 ±1.28* 35.32 ±1.55 47.53 ±3.24 49.14 ±2.36 43.17 ±2.12 47.81 ±4.18 44.29 ±2.09 41.52 ±2.46 107.56 ±3.80 103.96 ±2.88 111.49 ±4.95 62.74 ±2.71 59.57 ±1.70 64.06 ±4.52 65.53 ±3.92 64.93 ±1.91 70.28 ±4.93 39.68 ±2.17 44.77 ±2.39 44.30 ±1.87 56.67 ±1.08 57.18 ±0.83 60.12 ±2.05 36.46 ±2.47 37.58 ±2.64 40.44 ±5.11. pnd 5 43.88 ±2.19 43.46 ±1.65 41.43 ±3.07 46.08 ±1.64 47.96 ±2.82 47.18 ±2.20 42.39 ±2.66 50.62 ±3.63* 45.10 ±2.37 98.64 ±5.54 111.26 ±3.15 112.44 ±5.72 58.07 ±3.71 63.36 ±3.23 63.24 ±3.84 68.85 ±3.19 69.82 ±3.37 80.88 ±3.39*# 39.11 ±1.97 45.14 ±2.25 39.98 ±1.97 56.53 ±1.63 56.26 ±1.60 58.63 ±1.23 38.76 ±2.54 40.77 ±2.23 38.70 ±1.82. /POTFQBSBUFE /4&1  CBTBM BOE NBUFSOBM TFQBSBUJPO JOEVDFE N3/" FYQSFTTJPO MFWFMT PG DFOUSBM )1" BYJT NBSLFSTJONPVTFQVQTUFTUFEBUEJĒFSFOUBHFT 4FF'JHVSFGPSBOFYQMBOBUJPOPGUIFEJĒFSFOUUSFBUNFOUHSPVQT  3FMBUJWFPQUJDBMEFOTJUZMFWFMTPGN3/"FYQSFTTJPOBSFFYQSFTTFEJOBSCJUSBSZVOJUT"MMEBUBQSFTFOUFEBTNFBO™ 4&. *1 TJHOJêDBOUGSPNi/4&1uBUUIFTBNFEBZ #1 WFSTVTiCBTBMuBUUIFTBNFEBZ . .

(13) Chapter 2 BHFBOEUSFBUNFOUJOUIF$"BSFB '   1 )PXFWFS POMZJOUIF%(BѫFSUIFUIJSE QFSJPEPGTFQBSBUJPO BUQOE .3N3/"FYQSFTTJPOTJHOJêDBOUMZJODSFBTFEDPNQBSFEUPOPO TFQBSBUFEBOJNBMT 1 ѮFSFXBTBMTPBUSFOEUPXBSETBTJHOJêDBOUJODSFBTFDPNQBSFEUP CBTBMMFWFMT 1 #BTBM.3N3/"FYQSFTTJPOBѫFSFBDITVDDFTTJWFQFSJPEPGTFQBSBUJPOXBT OPUBĒFDUFE (3N3/"JO17/ QJUVJUBSZBOEIJQQPDBNQVT 5BCMF. *OUIF17/BOEUIFQJUVJUBSZ DPOTFDVUJWFIPVSTNBUFSOBMTFQBSBUJPOTBUQOET BOEEJEOPU MFBEUPBOBMUFSFE(3N3/"FYQSFTTJPO OFJUIFSEJEJUBĒFDUCBTBMFYQSFTTJPO . *OUIFIJQQPDBNQVTXFXFSFPOMZBCMFUPNFBTVSF(3N3/"FYQSFTTJPOJOUIF$"TVCêFME. BUUIFTFBHFT QOETm TFFBMTP<> *OUIF$"BOE%(TVCêFMETPGUIFIJQQPDBNQVT(3 N3/"FYQSFTTJPOXBTWFSZMPXBOESFNBJOFECFMPXUIFEFUFDUJPOMJNJU(3N3/"FYQSFTTJPO XBTOPUBMUFSFECZDPOTFDVUJWFQFSJPETPGNBUFSOBMTFQBSBUJPOPSBHF OPSEJETFQBSBUJPOBĒFDU CBTBMFYQSFTTJPOMFWFMT. &YQFSJNFOU**XBTEFTJHOFEUPDPNQBSFUIFUJNFDPVSTFPGUIFFĒFDUPGBTJOHMFIPVST NBUFSOBM TFQBSBUJPO BU QOE  XJUI UIF PVUDPNF PG UISFF DPOTFDVUJWF EBJMZ  IPVST NBUFSOBM TFQBSBUJPOTBUQOET BOE NFBTVSFEBUQOE $PSUJDPTUFSPOF 'JHVSF". 8FPCTFSWFEBNBJOFĒFDUPGUSFBUNFOU '   1 UJNF '   1  BOE BO JOUFSBDUJPO CFUXFFO USFBUNFOU BOE UJNF '    1  JOEJDBUJOH UIBU BT B DPOTFRVFODFPGQSFWJPVTFYQFSJFODFTPGUIFQVQT UIFUJNFDPVSTFPGDPSUJDPTUFSPOFTFDSFUJPOPWFS IPVSTPGNBUFSOBMBCTFODFXBTDIBOHFEѮFUISFFUJNFTTFQBSBUFEHSPVQOPMPOHFSSFTQPOEFE UPTFQBSBUJPOXJUIBOJODSFBTFJODPSUJDPTUFSPOFBOEIBEMPXFSQMBTNBDPODFOUSBUJPOTBU BOEIPVSTDPNQBSFEUPOPOTFQBSBUFEBOJNBMT 1 BOEBUBMMUJNFQPJOUTDPNQBSFE UPêSTUUJNFTFQBSBUFEBOJNBMT 1 0OUIFPUIFSIBOE BOJNBMTTFQBSBUFEGPSUIFêSTUUJNF TIPXFEBOJODSFBTFJODPSUJDPTUFSPOFUIJTJODSFBTFPOMZTUBSUFEBѫFSIPVSTPGNBUFSOBMBCTFODF BUIPVST  . 1PTU IPD BOBMZTFT BMTP TIPXFE UIBU DPSUJDPTUFSPOF NFBTVSFE BU  IPVST JO BOJNBMT. TFQBSBUFEGPSUIFêSTUPSUIFUIJSEUJNFXFSFTJHOJêDBOUMZIJHIFSUIBUUIPTFNFBTVSFEBU IPVST 1XJUIJOFBDIUSFBUNFOUHSPVQ  "$5) 'JHVSF#. 8FPCTFSWFEBNBJOFĒFDUPGUSFBUNFOU '   1 UJNF '   1  BOE BO JOUFSBDUJPO CFUXFFO USFBUNFOU BOE UJNF '    1  JOEJDBUJOH UIBU UIF SFTQPOTFUPIPVSTNBUFSOBMTFQBSBUJPOBUQOEEFQFOEFEPOUIFQSFWJPVTFYQFSJFODFPGUIF QVQT1VQTTFQBSBUFEGPSUIFUIJSEUJNFEJEOPUEJĒFSGSPNOPOTFQBSBUFEBOJNBMTBUBOZUJNF QPJOU "OJNBMT TFQBSBUFE GPS UIF êSTU UJNF  IPXFWFS  EJE TIPX BO JODSFBTF JO QMBTNB "$5) .

(14) $IBQUFS A. B. 'JHVSF $PSUJDPTUFSPOF " BOE"$5) # SFTQPOTFUPIPVSTNBUFSOBMTFQBSBUJPOBUQOEJOBOJNBMTXJUIOPQSFWJPVT IJTUPSZPGTFQBSBUJPO TUTFQBSBUJPO BOEJOBOJNBMTQSFWJPVTMZFYQPTFEUPIPVSTTFQBSBUJPOBUQOETBOE SE TFQBSBUJPO /POTFQBSBUFEBOJNBMT /4&1 XFSFMFѫVOEJTUVSCFEVOUJMUIFNPNFOUPGUFTUJOH"UIPVST TUBSU PGTFQBSBUJPOQFSJPE POFHSPVQPGBOJNBMTTFSWFEBTBCBTBMNFBTVSFNFOUGPSCPUIUIFiOPOTFQBSBUFEuBOEiTU TFQBSBUJPOuHSPVQ%BUBSFQSFTFOUNFBO™4&.*1 TJHOJêDBOUGSPNiTUTFQBSBUJPOu #1 TJHOJêDBOU GSPN CPUI DMPTFTUiOPOTFQBSBUFEuHSPVQ T. †1 TJHOJêDBOUGSPNIPVST XJUIJOUSFBUNFOUHSPVQ . MFWFMTDPNQBSFEUPOPOTFQBSBUFEBOJNBMT"$5)TUBSUFEUPSJTFUPIPVSTBѫFSUIFPOTFUPG TFQBSBUJPO BUmIPVST. . 1PTUIPDBOBMZTFTBMTPTIPXFEUIBU"$5)WBMVFTNFBTVSFEBUIPVSTJOFJUIFSHSPVQ. XFSFTJHOJêDBOUMZIJHIFSUIBOBUIPVST 1XJUIJOFBDIUSFBUNFOUHSPVQ  &YQFSJNFOU***XBTEFTJHOFEUPEFUFSNJOFXIFUIFSUIFBCTFODFPGUIFFOEPDSJOFSFTQPOTFUP BUIJSEQFSJPEPGNBUFSOBMTFQBSBUJPOBTPCTFSWFEJO&YQFSJNFOU*XBTBHFTQFDJêD CZSFQFBUJOH UIJTFYQFSJNFOUOPXJODMVEJOHBTJOHMFNBUFSOBMTFQBSBUJPOBUQOETBOE $PSUJDPTUFSPOF 'JHVSF". 8FPCTFSWFEBNBJOFĒFDUPGUSFBUNFOU '   1 UJNF '   1 BOE BOJOUFSBDUJPOCFUXFFOUSFBUNFOUBOEUJNF '   1 JOEJDBUJOHUIBUUIFSFTQPOTFUP NBUFSOBMTFQBSBUJPO UJNF DIBOHFE EFQFOEJOHPOUIFBNPVOUPGDPOTFDVUJWFTFQBSBUJPOQFSJPET .

(15) Chapter 2 USFBUNFOU *SSFTQFDUJWFPGUIFBHFPGUIFBOJNBMT QVQTSFBDUFEXJUIBOJODSFBTFJODPSUJDPTUFSPOF UPUIFêSTUQFSJPEPGNBUFSOBMTFQBSBUJPO BMMBHFT1 'VSUIFSNPSF JOSFTQPOTFUPFBDI TVDDFTTJWF QFSJPE PG TFQBSBUJPO UIF NBHOJUVEF PG DPSUJDPTUFSPOF TFDSFUJPO EFDSFBTFE TFDPOE TFQBSBUJPOBUQOE 1 VOUJMJUEJTBQQFBSFE UIJSETFQBSBUJPOBUQOE  "$5) 'JHVSF#. 8FPCTFSWFEBNBJOFĒFDUPGUSFBUNFOU '   1 UJNF '   1 BOE BOJOUFSBDUJPOCFUXFFOUSFBUNFOUBOEUJNF '   1 JOEJDBUJOHUIBUEFQFOEJOHPO UIFBNPVOUPGDPOTFDVUJWFTFQBSBUJPOQFSJPETUIF"$5)SFTQPOTFUPIPVSTNBUFSOBMBCTFODF DIBOHFE5PUIFêSTUUJNFNBUFSOBMTFQBSBUJPOXFEFUFDUFEBOJODSFBTFJO"$5) JSSFTQFDUJWFPG BHF BMMBHFT1 'VSUIFSNPSF UPUIFTFDPOEQFSJPEPGTFQBSBUJPOUIFNBHOJUVEFPG"$5) SFTQPOTFEFDSFBTFE QOE 1 XIFSFBTBUIJSEFYQPTVSFHBWFBOFWFOTNBMMFS UIPVHITUJMM TJHOJêDBOUSFTQPOTF QOE 1  A. B. 'JHVSF /POTFQBSBUFE /4&1 CBTBMBOENBUFSOBMTFQBSBUJPOJOEVDFEQMBTNBDPSUJDPTUFSPOF " BOE"$5) # MFWFMT JONPVTFQVQTUFTUFEBUEJĒFSFOUBHFT iTUuêSTUIPVSTPGNBUFSOBMTFQBSBUJPOBUQOET PSiOE uTFQBSBUFE BUQOETBOEiSE uTFQBSBUFEBUQOET BOETFFBMTP'JHVSFGPSBEFUBJMFEFYQMBOBUJPOPOUIFUSFBUNFOU HSPVQT %BUBSFQSFTFOUNFBO™4&. *1  TJHOJêDBOUGSPNi/4&1uPSiCBTBMuXJUIJOUIFTBNFUSFBUNFOU HSPVQBUUIFTBNFEBZ . .

(16) $IBQUFS A. B. 'JHVSF #BTBM TFQBSBUJPOBOEOPWFMUZ NJOVUFTJTPMBUFEFYQPTVSFUPBOFXFOWJSPONFOU JOEVDFEQMBTNBDPSUJDPTUFSPOF " BOE"$5) # MFWFMTBUQOE/4&1BOETU4&1IBEOPQSFWJPVTIJTUPSZPGUSFBUNFOUTSE4&1BOJNBMTXFSF FYQPTFEUPIPVSTTFQBSBUJPOBUQOETBOESE4&1

(17) /BOJNBMTXFSFFYQPTFEUPIPVSTNBUFSOBMTFQBSBUJPO EJSFDUMZGPMMPXFECZNJOVUFTOPWFMUZBUQOETBOEi4FQBSBUJPOuMFWFMTPGTU4&1 SE4&1BOESE4&1

(18) /XFSF NFBTVSFEBUUIFFOEPGIPVSTNBUFSOBMTFQBSBUJPO%BUBSFQSFTFOUNFBO™4&.*1 TJHOJêDBOUGSPN CBTBMPSTFQBSBUFE #1 TJHOJêDBOUGSPN/4&1 . &YQFSJNFOU*7XBTEFTJHOFEUPEFUFSNJOFXIFUIFSDPSUJDPTUFSPOFBOE"$5)TUJMMSFTQPOEFE UPFYQPTVSFPGBOBEEJUJPOBMOPWFMUZTUSFTTPSEJSFDUMZBѫFSNBUFSOBMTFQBSBUJPO $PSUJDPTUFSPOF 'JHVSF". 8F PCTFSWFE BO FĒFDU PG USFBUNFOU '    1  UJNF '    1  BOE BOJOUFSBDUJPOCFUXFFOUSFBUNFOUBOEUJNF '   1 %FQFOEJOHPOUIFUSFBUNFOU UIFQVQTSFDFJWFE UIFJSSFTQPOTFUPOPWFMUZDIBOHFE"TFYQFDUFE OPOTFQBSBUFEBOJNBMTXFSF OPUBCMFUPSFTQPOEUPOPWFMUZXJUIBSJTFJODPSUJDPTUFSPOF XIFSFBTQVQTTFQBSBUFEGSPNUIFJS NPUIFSGPSUIFêSTUUJNFXFSFBCMFUPSFTQPOEUPOPWFMUZFWFOUIPVHIDPSUJDPTUFSPOFMFWFMTXFSF BMSFBEZJODSFBTFEEVFUPUIFQSFDFEJOHTFQBSBUJPO . ѮPVHIQVQTUIBUXFSFTFQBSBUFEGPSUISFFUJNFTIBEDPSUJDPTUFSPOFMFWFMTTJNJMBSUPUIPTF. PCTFSWFE GPS VOUSFBUFE BOJNBMT  UIFZ XFSF TUJMM DBQBCMF UP SFTQPOE UP OPWFMUZ "MTP QVQT UIBU XFSF SFQFBUFEMZ TFQBSBUFE JO DPNCJOBUJPO XJUI OPWFMUZ FYQPTVSF BѫFS FBDI TFQBSBUJPO QFSJPE SE4&1

(19) / TUJMMSFTQPOEFEUPOPWFMUZѮFJSDPSUJDPTUFSPOFMFWFMTBѫFSUIFUIJSETFQBSBUJPOXFSF .

(20) Chapter 2 TJHOJêDBOUMZIJHIFSUIBOUIPTFPGOPOTFQBSBUFEBOJNBMT /4&1 CVUOPUDPNQBSFEUPUIPTFPG UIFSFQFBUFETFQBSBUJPOHSPVQXJUIPVUOPWFMUZFYQPTVSF SE4&1  "$5) 'JHVSF#. 8F PCTFSWFE B NBJO FĒFDU PG USFBUNFOU '    1  BOE UJNF '    1  "MUIPVHI "$5) MFWFMT PG QVQT TFQBSBUFE GPS UIF êSTU UJNF XFSF BMSFBEZ IJHIFS UIBO UIPTF PG OPOTFQBSBUFEQVQT BOJNBMTJOCPUIHSPVQTXFSFVOBCMFUPSFTQPOEUPOPWFMUZXJUIBOJODSFBTF JO"$5) . "OJNBMT TFQBSBUFE GPS UISFF UJNFT SE 4&1  IBE IJHIFS "$5) MFWFMT DPNQBSFE UP OPO. TFQBSBUFEBOJNBMTBOESFTQPOEFEUPOPWFMUZXJUIBGVSUIFSJODSFBTFJO"$5)*OQVQTSFDFJWJOH NBUFSOBMTFQBSBUJPOJODPNCJOBUJPOXJUIOPWFMUZFBDIUJNF SE4&1

(21) / TIPXFE BѫFSUIFUIJSE TFQBSBUJPOQFSJPE "$5)MFWFMTTJNJMBSUPUIPTFPGOPOTFQBSBUFEBOJNBMTBOEUIFFYQPTVSFUPB OPWFMUZTUSFTTPSEJEOPUFWPLFBSFTQPOTF &YQFSJNFOU7ѮFPCKFDUJWFXBTUPEFUFSNJOFDJSDVMBUJOHHISFMJOBOEHMVDPTFDPODFOUSBUJPOT JO SFTQPOTF UP SFQFBUFE NBUFSOBM TFQBSBUJPOT $PSUJDPTUFSPOF BOE N3/" FYQSFTTJPO PG DGPT N3/"XFSFBMTPNFBTVSFEVOEFSCBTBMDPOEJUJPOTBOEJOSFTQPOTFUPNBUFSOBMTFQBSBUJPOTXJUI BOEXJUIPVUOPWFMUZFYQPTVSF $PSUJDPTUFSPOF 'JHVSF. "NBJOFĒFDUXBTPCTFSWFEPGUSFBUNFOU '   1 UJNF '   1  BOEBOJOUFSBDUJPOCFUXFFOUIFTFGBDUPST '   1 *OSFTQPOTFUPBêSTUTFQBSBUJPO QFSJPE DPSUJDPTUFSPOF JODSFBTFE 1  BOE UIFTF MFWFMT JODSFBTFE FWFO GVSUIFS XIFO QVQT XFSFTVCKFDUFEUPBEEJUJPOBMOPWFMUZTUSFTT 1 *OSFTQPOTFUPBUIJSEQFSJPEPGTFQBSBUJPO  IPXFWFS DPSUJDPTUFSPOFWBMVFTEJEOPUBMUFS UIPVHIFYQPTVSFUPBOPWFMFOWJSPONFOUXBTBCMF UPBDUJWBUFUIF)1"BYJT 1 #BTBMDPSUJDPTUFSPOFBUUIFTUBSUPGFJUIFSUIFêSTUPSUIJSE TFQBSBUJPOQFSJPEEJEOPUEJĒFS. 'JHVSF $PSUJDPTUFSPOF JO BOJNBMT BU QOE  XJUI OP QSFWJPVT IJTUPSZ PG TFQBSBUJPO TU 4&1  BOE JO BOJNBMT QSFWJPVTMZ FYQPTFEUPIPVSTTFQBSBUJPOTBUQOETBOE SE4&1 $PSUJDPTUFSPOFSFTQPOTFXBTNFBTVSFEBѫFSIPVSTPG NBUFSOBMTFQBSBUJPOBOEBѫFSIPVSTPGNBUFSOBMTFQBSBUJPOXJUIBOBEEJUJPOBMNJOVUFTPGOPWFMUZTUSFTT%BUB SFQSFTFOUNFBO™4&.*1 TJHOJêDBOUGSPNCBTBM #1 TJHOJêDBOUGSPNTFQBSBUFE . .

(22) $IBQUFS A. B. 'JHVSF (MVDPTF "  BOE HISFMJO #  SFTQPOTF UP NBUFSOBM TFQBSBUJPO BU QOE  JO BOJNBMT XJUI OP QSFWJPVT IJTUPSZ PG TFQBSBUJPOT TU 4&1  BOE JO BOJNBMT QSFWJPVTMZ FYQPTFE UP  IPVST TFQBSBUJPO BU QOET  BOE  SE 4&1  %BUB SFQSFTFOUNFBO™4&.*1 TJHOJêDBOUGSPNCBTBM . (MVDPTF 'JHVSF". "NBJOFĒFDUPGUJNFXBTEFUFSNJOFE '   1 CVUOPUPGUSFBUNFOU*OSFTQPOTF UPBêSTUNBUFSOBMTFQBSBUJPOQFSJPECMPPEHMVDPTFMFWFMTEFDSFBTFEUPBMNPTUIBMGUIFJSPSJHJOBM MFWFMT 1 "ѫFSSFQFBUFETFQBSBUJPOTUIJTTBNFSFTQPOTFXBTTUJMMQSFTFOU 1 #BTBM HMVDPTFWBMVFTXFSFTJNJMBSCFUXFFOUIFBOJNBMTTFQBSBUFEGPSUIFêSTUPSUIJSEUJNF. 5BCMFN3/"FYQSFTTJPOPGDGPTJOTFMFDUFECSBJOBSFBT. Cortex pPVTh. 1st SEP 3rd SEP 1st SEP 3rd SEP. basal 14.63 ±2.09 12.34 ±2.56 40.76 ±2.56 39.76 ±4.50. separated 13.92 ±2.22 11.70 ±2.15 39.35 ±4.31 31.85 ±2.55. novelty 15.10 ±3.28 12.00 ±0.92 40.08 ±3.61 32.39 ±1.7. 5PEFUFSNJOFDFOUSBMBDUJWBUJPOPGOFVSPOTJOSFTQPOTFUPNBUFSOBMTFQBSBUJPOBOEBEEJUJPOBMOPWFMUZTUSFTTDGPT N3/"FYQSFTTJPOXBTEFUFSNJOFEJOUIF17/ 'JHVSF DPSUFYBOEQ17Ѯ QBSBWFOUSJDVMBSUIBMBNJDOVDMFVT  %BUBBSFFYQSFTTFEBTPQUJDBMEFOTJUZNFBTVSFEJOBSCJUSBSZVOJUTBOEQSFTFOUFEBTNFBO™4&.. .

(23) Chapter 2. 'JHVSF $GPTN3/"FYQSFTTJPONFBTVSFEJOUIF17/BUQOEJOBOJNBMTXJUIOPQSFWJPVTIJTUPSZPGTFQBSBUJPO TU4&1  BOEJOBOJNBMTQSFWJPVTMZFYQPTFEUPIPVSTTFQBSBUJPOTBUQOETBOE SE4&1 &YQSFTTJPOXBTNFBTVSFEBѫFS IPVSTPGNBUFSOBMTFQBSBUJPOBOEBѫFSIPVSTPGNBUFSOBMTFQBSBUJPOXJUIBOBEEJUJPOBMNJOVUFTPGOPWFMUZ TUSFTT3FMBUJWFPQUJDBMEFOTJUZMFWFMTPGN3/"FYQSFTTJPOBSFFYQSFTTFEJOBSCJUSBSZVOJUT%BUBSFQSFTFOUNFBO™ 4&.*1 TJHOJêDBOUGSPNCBTBM #1 TJHOJêDBOUGSPNTFQBSBUFE . (ISFMJO 'JHVSF#. "NBJOFĒFDUPGUJNFXBTNFBTVSFE '   1 CVUOPUPGUSFBUNFOU(ISFMJOMFWFMT XFSF UXJDF BT IJHI BѫFS B êSTU 1  CVU BMTP BѫFS B UIJSE QFSJPE PG NBUFSOBM TFQBSBUJPO 1 BTDPNQBSFEUPCBTBMMFWFMT#BTBMMFWFMTXFSFJOEJTUJOHVJTIBCMFCFUXFFOCPUIUSFBUNFOU HSPVQT DGPTN3/"FYQSFTTJPO 'JHVSF 5BCMF. ѮFFYQSFTTJPOPGDGPTN3/"JOUIF17/TIPXFEBNBJOFĒFDUPGUJNF '   1  *OSFTQPOTFUPNBUFSOBMTFQBSBUJPODGPTN3/"FYQSFTTJPOJODSFBTFEJOUIFBOJNBMTTFQBSBUFE GPSUIFêSTUUJNF 1 XIFSFBTJUEJEOPUSFTQPOEJOUIFUIJSEUJNFTFQBSBUJPOHSPVQ#BTBM MFWFMTXFSFDPNQBSBCMFCFUXFFOCPUIUSFBUNFOUHSPVQT6QPOFYQPTVSFUPBOPWFMFOWJSPONFOU GPSNJOVUFTDGPTN3/"FYQSFTTJPOJODSFBTFEUPDPNQBSBCMFMFWFMTJOBOJNBMTTFQBSBUFECPUI GPSUIFêSTUBOEUIJSEUJNF 1 $GPTN3/"FYQSFTTJPOJOUIFDPSUFYBOEJOUIFQ17Ѯ QBSBWFOUSJDVMBSUIBMBNJDOVDMFVT XBTVOBĒFDUFECZUSFBUNFOUPSUJNF. %JTDVTTJPO ѮF QSFTFOU TUVEZ TIPXT JO $% NJDF UIBU UIF JOGBOU NPVOUT B MBSHF SFTQPOTF PG "$5) BOE DPSUJDPTUFSPOFBѫFSIPVSTPGTFQBSBUJPOGSPNUIFNPUIFS$POUSBSZUPPVSFYQFDUBUJPOT EBJMZ SFQFBUFE TFQBSBUJPOT PG  IPVST SFBEJMZ BCPMJTIFE UIF QJUVJUBSZBESFOBM SFTQPOTF  QSPEVDJOH DPSUJDPTUFSPOFMFWFMTUIBUXFSFFWFODPOTJTUFOUMZMPXFSIPVSTBѫFSSFVOJPO)PXFWFS EFTQJUF UIFBCTFODFPGBO)1"SFTQPOTFUPSFQFBUFETFQBSBUJPOT UIFEFQSJWFEQVQDPOUJOVFEUPSFTQPOE UPOPWFMUZѮFêOEJOHUIBUUIFSFTQPOTFUPNVMUJQMFTFQBSBUJPOTXBTSFEVDFECFMPXDPOUSPMMFWFMT  XIJMF TUSFTT SFTQPOTJWFOFTT SFNBJOFE FOIBODFE  JOEJDBUFT QSPOPVODFE EJĒFSFOU FĒFDUT PO UIF .

(24) $IBQUFS OFVSPFOEPDSJOFTZTUFNTPGUIFOFXCPSOUIBUSFHVMBUFCBTBMTFDSFUJPOTBTPQQPTFEUPUIPTFUIBU SFRVJSFNJMETUSFTTPST . ѮFSFTVMUTPGUIJTTUVEZSFKFDUUIFIZQPUIFTJTUIBUEBJMZTFQBSBUJPOTXPVMEMFBEUPBOFOIBODFE. BESFOBM DPSUJDPTUFSPOF PVUQVU 4VSQSJTJOHMZ  UIF )1" BYJT SBQJEMZ EFTFOTJUJTFE .PSFPWFS   IPVST BѫFS SFVOJPO DPSUJDPTUFSPOF MFWFMT XFSF DPOTJTUFOUMZ MPXFS BOE UIJT TUBUF PG SFEVDFE DPSUJDPTUFSPOFQFSTJTUFEPWFSUIFOFYUUXPEBZT3FDFOUMZ UIFSFIBTCFFOBOJODSFBTFEBXBSFOFTT PG UIF TJHOJêDBODF PG IZQPDPSUJTPMJTN  TJODF UIFSF JT B SFEVDFE DPSUJTPM TFDSFUJPO PCTFSWFE JO DIJMESFOFYQPTFEUPBEWFSTFFBSMZMJGFFYQFSJFODF<  >ѮJTTUVEZJTUIFêSTUEFNPOTUSBUJPO UIBU UIF TBNF QIFOPNFOPO BMTP PDDVST JO SPEFOUT *U SBJTFT UIF JOUSJHVJOH QPTTJCJMJUZ UIBU B AOPSNBMHMVDPDPSUJDPJEMFWFMJTSFRVJSFEGPSCSBJOEFWFMPQNFOUBOEUIBUFJUIFSUPPMPXPSUPP IJHIMFWFMTNBZIBWFEFUSJNFOUBMFĒFDUT . *O&YQFSJNFOU* BOIPVSTFQJTPEFPGNBUFSOBMTFQBSBUJPOXBTVTFEUPFOTVSFBOBDUJWBUJPO. PG UIF QVQT )1" BYJT <    > 8IFO JU BQQFBSFE UIBU BѫFS UISFF EBJMZ QFSJPET PG  IPVST NBUFSOBM TFQBSBUJPO UIF FOEPDSJOF SFTQPOTF BTTPDJBUFE XJUI NBUFSOBM BCTFODF XBT OP MPOHFS QSFTFOU  BU êSTU B QPTTJCMF TIJѫ JO UJNF DPVSTF PG UIF SFTQPOTF XBT JOWFTUJHBUFE &YQFSJNFOU ** ѮFSFBTPOJOHXBTUIBUSFQFBUFETFQBSBUJPOTNJHIUIBWFGBDJMJUBUFEUIFPOTFUPGBUSBOTJFOU )1"SFTQPOTFUPBOFBSMJFSUJNFQPJOUXJUIDPSUJDPTUFSPOFMFWFMTSFUVSOJOHBMSFBEZUPCBTFMJOFBU UIFIPVSTJOUFSWBMSFDPSEFEJOUIFêSTUFYQFSJNFOUѮFUJNFDPVSTFTUVEZEFNPOTUSBUFEUIBU UIFSFXBTOPFBSMJFSSFTQPOTFBOEUIBUUIFIPVSJOUFSWBMXBTBQQSPQSJBUFUPSFMJBCMZNPOJUPS EFTFOTJUJTBUJPOPGUIF"$5)BOEDPSUJDPTUFSPOFSFTQPOTFUPSFQFBUFETFQBSBUJPOT . ѮFUJNFDPVSTFFYQFSJNFOUJOWPMWJOHIPVSFQJTPEFTBMTPTIPXFEBѫFSUIFêSTUTFQBSBUJPO. UIBUUIFJOJUJBM"$5)FMFWBUJPOPDDVSFEBѫFSIPVST XIFSFBTDPSUJDPTUFSPOFTUBSUFEUPSJTFPOMZ BѫFSIPVSTѮJTJOEJDBUFEUIBUUIF)1"BYJTSFTQPOEFETMPXMZUPNBUFSOBMTFQBSBUJPOBOEUIBU JUUPPLBGFXIPVSTPG"$5)TUJNVMBUJPOCFGPSFUIFTUSPOHMZSFEVDFEBESFOBMTFOTJUJWJUZUP"$5) EVSJOHUIF4)31XBTPWFSDPNFѮJTPCTFSWBUJPOJTJOTVQQPSUPGQSFWJPVTTUVEJFT<  > . &YQFSJNFOU ** BMTP EFNPOTUSBUFE UIBU  JG JNNFEJBUFMZ BѫFS TFQBSBUJPO UIF JOGBOUT XFSF. BMTPFYQPTFEUPBNJOVUFTOPWFMUZTUSFTTPS BQSPGPVOE"$5)BOEDPSUJDPTUFSPOFSFTQPOTF PDDVSFEVOEFSDPOEJUJPOTUIBUUIFQVQT)1"SFTQPOTFUPSFQFBUFETFQBSBUJPOTXBTBCPMJTIFE Ѯ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ѮFEBUBTIPXFEUIBUUIFFOEPDSJOFSFTQPOTFUPNBUFSOBMTFQBSBUJPO HSBEVBMMZEJNJOJTIFEXJUIFBDITVDDFTTJWFTFQBSBUJPOGPSCPUIDPSUJDPTUFSPOFBOE"$5)JFUIF .

(25) Chapter 2 SFTQPOTFTBUQOEXFSFMPXFSBTDPNQBSFEUPQOEѮFFYQFSJNFOUDPOêSNFEUIBUCBTBMMFWFMT PG DPSUJDPTUFSPOF BOE "$5) BU  IPVST BѫFS SFVOJPO XFSF FWFO MPXFS JG DPNQBSFE UP OPO TFQBSBUFEBOJNBMT'VSUIFSNPSF XFPCTFSWFEUIBUUIFFOEPDSJOFSFTQPOTFUPBTJOHMFTFQBSBUJPO XBTQSFTFOUBUQOET BOE MJLFQSFWJPVTMZXBTTIPXOGPSQOE<>ѮFTFSFTVMUTJOEJDBUF UIBUUIFQVQTUSVMZEFTFOTJUJTFUPEBJMZNBUFSOBMBCTFODFBOEUIBUUIJTEFTFOTJUJTBUJPOJTOPUBHF TQFDJêD  4JODFJUXBTBMSFBEZTIPXOBUQOEUIBUN3/"FYQSFTTJPOPGDFOUSBM)1"BYJTNBSLFST XFSFSFTQPOTJWFUPIPVSTPGNBUFSOBMBCTFODF TFWFSBMPGUIFTFNBSLFSTXFSFFYBNJOFEJOPVS QBSBEJHNJOPSEFSUPêOEDMVFTUPXBSETUIFDBVTFPGUIFPCTFSWFEEFTFOTJUJTBUJPO"UQOE$3) N3/"FYQSFTTJPOJOUIF17/EFDSFBTFEBMSFBEZBѫFSIPVSTPGNBUFSOBMBCTFODF< >*O PVSQBSBEJHNVTJOHEBZTPMENJDF$3)N3/"JOUIF17/POMZSFTQPOEFEUPUIFêSTUQFSJPE PGNBUFSOBMBCTFODFBUIPVSTBѫFSSFVOJPO4JODF$3)N3/"FYQSFTTJPOJTDPSUJDPTUFSPOF SFTQPOTJWF< > UIJTEPXOSFHVMBUJPOJO$3)N3/"FYQSFTTJPONJHIUCFBDPOTFRVFODFPGUIF IJHIDPSUJDPTUFSPOFDPODFOUSBUJPOTJOEVDFECZUIFêSTUTFQBSBUJPOQFSJPE$PODPNJUBOUMZ UIF QSPHSFTTJWFBUUFOVBUJPOPGUIFDPSUJDPTUFSPOFSFTQPOTFEVSJOHUIFTFDPOEBOEUIJSETFQBSBUJPO  SFTQFDUJWFMZ NJHIUIBWFCFFOQFSNJTTJWFGPS$3)N3/"FYQSFTTJPOMFWFMTUPSFTUPSF"MUFSOBUJWFMZ  MPXFS$3)N3/"FYQSFTTJPOSFëFDUTUIFMPXFSCBTBM"$5)BOEDPSUJDPTUFSPOFMFWFMTBUUIFTUBSU PGUIFTFDPOETFQBSBUJPOQFSJPE)PXFWFS UIFEFDSFBTFE$3)N3/"MFWFMSFDPWFSFEBѫ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êDLOPDLPVUNJDF.3N3/"FYQSFTTJPOJTEFDSFBTFE<> ѮPVHIXFEJEOPUNFBTVSF$3)MFWFMTJOMJNCJDSFHJPOTCFZPOEUIF17/ UIF$3)STZTUFN QSFTFOUTBHPPEDBOEJEBUFGPSUIFGBDJMJUBUFEEFWFMPQNFOUBMJODSFBTFJO.3N3/"FYQSFTTJPOJO SFQFBUFEMZTFQBSBUFENJDF  ѮF BCTFODF PG BO FOEPDSJOF SFTQPOTF UP B UIJSE NBUFSOBM TFQBSBUJPO BOE UIF FOIBODFE SFTQPOTFUPOPWFMUZEJSFDUMZGPMMPXJOHUIJTUIJSETFQBSBUJPOTFFNTUPJOEJDBUFUIBUUIFTFNPVTF QVQTBSFBCMFUPEJTTPDJBUFCFUXFFONBUFSOBMBCTFODFPOUIFPOFIBOEBOEUIFTUSFTTPGBOPWFM FOWJSPONFOUPOUIFPUIFS5PJOWFTUJHBUFXIFUIFSXFUSVMZPCTFSWFEEJTTPDJBUJPOCFUXFFOCPUI DPOEJUJPOT  XF BMTP UFTUFE JO &YQFSJNFOU *7 BOJNBMT JO XIJDI FBDI NBUFSOBM TFQBSBUJPO XBT MJOLFEUPBTVCTFRVFOUOPWFMUZFYQPTVSFGPSNJOVUFT*GQVQTXPVMEIBCJUVBUFUPUIFXIPMF QSPDFEVSF UIFSFTQPOTFUPOPWFMUZXPVMEOPMPOHFSCFQSFTFOUBѫFSiSFQFBUFETFQBSBUJPOTXJUI .

(26) $IBQUFS OPWFMUZ 4&1

(27) / u)PXFWFS GPSQVQTUSFBUFEXJUIUIJTQBSBEJHNBOPWFMFOWJSPONFOUXBTTUJMM TUSFTTGVMBUUIFUIJSEFYQPTVSF . *OUFSFTUJOHMZ UIF"$5)SFTQPOTFJOUIFUISFFUJNFTTFQBSBUJPOXJUIUISFFUJNFTOPWFMUZ. SE4&1

(28) / HSPVQXBTNVDIMFTTUIBOJOBOJNBMTUIBUXFSFPOMZTFQBSBUFEGSPNUIFJSNPSIUFST GPS UISFF UJNFT SE 4&1  "U UIF TBNF UJNF  UIF DPSUJDPTUFSPOF SFTQPOTF SFNBJOFE PG TJNJMBS NBHOJUVEF "QQBSFOUMZ QSPMPOHFE NBUFSOBM TFQBSBUJPO êSTU PWFSDPNFT UIF SFEVDFE BESFOBM TFOTJUJWJUZBTTPDJBUFEXJUIUIF4)31<  > XIFSFBTGVSUIFSTUJNVMBUJPOCZEBJMZFYQPTVSFUP BOPWFMFOWJSPONFOUUIFSFBѫFSFOIBODFTTFOTJUJWJUZPGUIFBESFOBMGPS"$5)Ѯ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ѮF DVSSFOU êOEJOHT SBJTF UIF RVFTUJPO XIZ UIF QJUVJUBSZBESFOBM SFTQPOTF DFBTFT BOE. CFDPNFTIZQPBDUJWFBѫFSSFQFBUFEEBJMZNBUFSOBMTFQBSBUJPOT0OFNFDIBOJTNDPVMECFSFMBUFE UPUIFQBUUFSOPGGPPEJOUBLF CFDBVTFGFFEJOHJTSFRVJSFEUPNBJOUBJOIZQPSFTQPOTJWFOFTTPG UIFBESFOBMUPTUSFTT< >&JHIUIPVSTPGGPPEEFQSJWBUJPOEFDSFBTFTDJSDVMBUJOHHMVDPTFBOE JODSFBTFTHISFMJOMFWFMT XIJMFBENJOJTUSBUJPOPGBHISFMJOBOUBHPOJTUDBOQSFWFOUUIFTFQBSBUJPO JOEVDFE)1"BDUJWBUJPO<>)FODF UIFOFYUIPVSTDPVMEIBWFMFEUPBOBMUFSFEQBUUFSOPGGPPE JOUBLFUIBUJTQFSIBQTSFëFDUFEJOUIFDJSDVMBUJOHMFWFMPGUIFTFNFUBCPMJDTJHOBMT&YQFSJNFOU 7 TIPXT UIBU BѫFS SFQFBUFE NBUFSOBM TFQBSBUJPOT HMVDPTF BOE HISFMJO MFWFMT TUJMM SFTQPOEFE TJNJMBSMZBTBѫFSUIFêSTUTFQBSBUJPOFWFOU BêOEJOHXIJDIJTOPUJOTVQQPSUPGBSPMFPGHISFMJOJO UIFEFTFOTJUJTBUJPOQSPDFTT'VSUIFSNPSF JGUIFSFXFSFBMUFSFEQBUUFSOTPGGPPEJOUBLFUIJTJTOPU SFGFMFDUFEJOUIFTFNFUBCPMJDTJHOBMT . 1MBTNB MFQUJO MFWFMT  SFMFWBOU JO SFMBUJPO UP HISFMJO <  >  XFSF OPU NFBTVSFE JO UIF. QVQT 1SFWJPVTMZ  4DINJEU FU BM <> TIPXFE UIBU QSFWFOUJOHUIF NBUFSOBM TFQBSBUJPOJOEVDFE EFDSFBTFJODJSDVMBUJOHMFQUJOMFWFMTDPVMEOPUQSFWFOUUIFQJUVJUBSZBESFOBMSFTQPOTFUPNBUFSOBM TFQBSBUJPO  XIJDI TVHHFTUT UIBU MFQUJO JT OPU JNQMJDBUFE )JHI MFWFMT PG MFQUJO JO UIF OFPOBUBM QFSJPEBSF IPXFWFS SFRVJSFEGPSUIFGPSNBUJPOPGQSPKFDUJPOQBUIXBZTGSPNUIFBSDVBUFOVDMFVT UPIZQPUIBMBNJDSFHJPOTUIBUSFHVMBUFGFFEJOHCFIBWJPVS<>$POTFRVFOUMZ JUJTDPODFJWBCMFUIBU SFQFBUFE NBUFSOBM TFQBSBUJPOT  XIJDI SFTVMU JO FQJTPEJD NFUBCPMJD SFTQPOTFT  DBO IBWF B XJEF SBOHFPGTUSVDUVSBMFĒFDUTXJUIMPOHUFSNDPOTFRVFODFTGPSCSBJOEFWFMPQNFOUBOEGVODUJPOJOH <> 'VSUIFS FYQFSJNFOUT BSF OFFEFE  XIJDI NBZ JODMVEF UIF BTTFTTNFOU PG HISFMJO SFDFQUPS FYQSFTTJPO JO UIF BSDVBUF OVDMFVT BT XFMM BT UIF SPMF PG MFQUJO JO TUSVDUVSBM SFNPEFMMJOH PG IZQPUIBMBNJDQBUIXBZT<> . "OPUIFSNFDIBOJTNNBZCFSFMBUFEUPUIFMBDLPGTFOTPSZTUJNVMBUJPO TJODFJUJTLOPXO. GPSTPNFUJNFUIBUUIFBDUJWBUJPOPGDFOUSBMDPNQPOFOUTPGUIF)1"BYJTPGUIFEFQSJWFEQVQ .

(29) Chapter 2 DBOCFQSFWFOUFECZTUSPLJOH<>.PSFPWFS VQPOSFVOJPOUIFQVQSFDFJWFTFYDFTTJWFNBUFSOBM DBSF  XIJDI BMTP DPVME BĒFDU )1" BDUJWBUJPO UIF OFYU EBZ &YQFSJNFOU 7 EFNPOTUSBUFE UIBU BѫFSSFQFBUFETFQBSBUJPOTUIFCBTBMDGPTN3/"SFTQPOTFJOUIF17/XBTBUUFOVBUFE CFDPNJOH JOEJTUJOHVJTIBCMFGSPNDPOUSPMT:FUUIF17/DGPTSFTQPOTFUPOPWFMUZSFNBJOFEGBDJMJUBUFEJOUIF TFQBSBUFEBOJNBMT XIJDIJTSFNJOJTDFOUUPUIFSFTQPOTFQBUUFSOPGUIF)1"BYJT*OUFSFTUJOHMZ  JOOFPOBUFSBUTIBOEMFEEBJMZGPSNJOVUFTGSPNQOETUP BOFOIBODFESFTQPOTFPGDGPT JNNVOPSFBDUJWJUZXBTPCTFSWFEJOUIF QBSBWFOUSJDVMBSUIBMBNJDOVDMFVT Q17ѮNFBTVSFE NJOVUFT BѫFS SFVOJPO BU QOE  BT DPNQBSFE UP VOEJTUVSCFE DPOUSPMT BOE QVQT IBOEMFE PODF POMZBUQOE<>*OUIFDVSSFOUTUVEZDGPTN3/"EJEOPUSFTQPOEJOQ17Ѯ BCSBJOSFHJPO JNQPSUBOU GPS SFMBZ PG TFOTPSZ JOGPSNBUJPO "MTP FMTFXIFSF JO UIF CSBJO XF EJE OPU êOE DGPT N3/"DIBOHFT . ѮBUDGPTN3/"JOUIFIZQPUIBMBNVTEJTQMBZTBDPSUJDPTUFSPOFMJLFSFTQPOTFQBUUFSOUP. SFQFBUFE TFQBSBUJPOT TVHHFTUT UIBU B DFOUSBM NFDIBOJTN JT JOWPMWFE *U NBZ XFMM CF UIBU FWFO UIFEBZTPMEJOGBOUDBOBMSFBEZQSFEJDUBѫFSPOFFYQFSJFODFUIBUUIFNPUIFSXJMMSFUVSOJO IPVSTѮFJOGBOUUIVTSBQJEMZBEBQUTPSIBCJUVBUFTUPNBUFSOBMBCTFODF CVUUIF)1"BYJTTUBZTPO BMFSUBOEDBOCFBDUJWBUFECZTUSFTTPST3FDFOUFWJEFODFTVHHFTUTJOEFFEUIBUMFBSOJOHDBOPDDVS JOOFPOBUBMSBUT<  >*OUIFTFTUVEJFTJUXBTGPVOEUIBUUIFêSTUXFFLPGMJGFBUUBDINFOU PGUIFJOGBOUUISPVHIPMGBDUPSZDVFTGSPNUIFNPUIFSEFQFOETPOBMPDVTDPFSVMFVTmPMGBDUPSZ QBUIXBZ*OUIFêSTUQPTUOBUBMXFFLJOGBOUSBUTSBQJEMZMFBSONBUFSOBMPEPSUPTVQQPSUBUUBDINFOU CFIBWJPVSBOEUPTVQQSFTTPEPSBWFSTJPOTEVSJOHUIBUUJNF*UJTPOMZJOUIFBCTFODFPGUIFNPUIFS UIBUBWFSTJWFPEPSTTUBSUUPBDUJWBUFUIFBNZHEBMBDJSDVJUUIBUHPWFSOTGFBSNPUJWBUFEBWPJEBODF ѮJT TXJUDI GSPN NBUFSOBM BUUSBDUJPO UP BWPJEBODF JT GBDJMJUBUFE CZ DPSUJDPTUFSPOF BOE DBO CF CMPDLFECZBHMVDPDPSUJDPJEBOUBHPOJTU*UJTDPODFJWBCMFUIBU TVDIBDPSUJDPTUFSPOFEFQFOEFOU NFDIBOJTNNBZGPSNUIFCBTJTGPSBEBQUJOHUPUIFUSBOTJFOUOBUVSFPGNBUFSOBMBCTFODF TJODFUIF JOGBOUJTTUJMMDBQBCMFUPNPVOUBDPSUJDPTUFSPOFSFTQPOTFVQPOFYQPTVSFUPOPWFMUZ . ѮFJNQMJDBUJPOTPGPVSêOEJOHTBSFWFSZJOUFSFTUJOH*UXPVMEJNQMZUIBUUIFPVUDPNFPG. UIFSFQFBUFENBUFSOBMTFQBSBUJPOTXPVMECF CFTJEFTHFOEFSBOETUSBJO OPUPOMZEFQFOEFOUVQPO UIFEVSBUJPOPGUIFTFQBSBUJPOBOEUIFNBUFSOBMDBSFSFDFJWFECZUIFQVQVQPOSFVOJPO CVUBMTP POUIFQVQTTUSFTTGVMFYQFSJFODFTEVSJOHUIFTFQBSBUJPOQSPDFEVSFѮBUNBUFSOBMDBSFJTOPUUIF TPMFGBDUPSEFUFSNJOJOHFQJHFOFUJDQSPHSBNNJOHBOEPVUDPNFXBTSFDFOUMZEFNPOTUSBUFEJOUIF FMFHBOUTUVEJFTPG.BDSJBOE8ÛSCFM< >ѮFSFGPSF TUBOEBSEJTBUJPOJOQSPUPDPMTVTFEGPS TUVEZPGUIFPVUDPNFPGNBUFSOBMTFQBSBUJPOTJTSFRVJSFE TJODFUIFDVSSFOUEBUBTIPXBEJĒFSFOU PVUDPNFJGUIFQVQJTSFNPWFE UIFEBN PSCPUI . *ODPODMVTJPO UIFDVSSFOUEBUBEFNPOTUSBUFUIFBNB[JOHDBQBDJUZPGUIFOFXCPSOSPEFOU. UPSFBEJMZBEBQUUPUIFBCTFODFPGUIFNPUIFSBOEQSFTFOUBTUSJLJOHFYBNQMFPGQMBTUJDJUZ TJODF UIFJOGBOUTSFNBJOSFTQPOTJWFUPOPWFMUZBOETFFNUPCFNBSLFECZBUPPMPXDJSDVMBUJOHBNPVOU PGDPSUJDPTUFSPOFѮFêOEJOHNBZCFIFMQGVMUPEFTJHOSBUJPOBMFYQFSJNFOUTUPVOEFSTUBOEUIF NFDIBOJTNVOEFSMZJOHUIFMBTUJOHFĒFDUTPGFBSMZBEWFSTJUZPOCSBJOBOECFIBWJPVS .

(30) $IBQUFS. "DLOPXMFEHFNFOUT ѮJT TUVEZ XBT TVQQPSUFE CZ UIF 3PZBM /FUIFSMBOET "DBEFNZ PG "SUT BOE 4DJFODFT  /80 45*(0//%3'BOE/808FXPVMEMJLFUPUIBOL*&.EF+POH  1(.WBO0WFSWFMEBOE14UFFOCFSHFOGPSUFDIOJDBMBTTJTUBODFXJUIUIFBOJNBMFYQFSJNFOUT. 3FGFSFODFT      .           . .  #PVSFU4( %SBQFS4+BOE4JNFSMZ3#  5SPQIJDBDUJPOPGMFQUJOPOIZQPUIBMBNJD OFVSPOTUIBUSFHVMBUFGFFEJOH4DJFODF    $IFDLMFZ 4   ѮF OFVSPFOEPDSJOPMPHZ PG EFQSFTTJPO BOE DISPOJD TUSFTT #S .FE #VMM    EF,MPFU&3BOE0JU[M.4  8IPDBSFTGPSBTUSFTTFECSBJO ѮFNPUIFS UIFLJEPS CPUI /FVSPCJPM"HJOH4VQQM44  EF,MPFU&3 7SFVHEFOIJM& 0JU[M.4BOE+PFMT.  #SBJODPSUJDPTUFSPJESFDFQUPS CBMBODFJOIFBMUIBOEEJTFBTF&OEPDS3FW    &EXBSET)&BOE#VSOIBN8.  ѮFJNQBDUPGDPSUJDPTUFSPJETPOUIFEFWFMPQJOH BOJNBM1FEJBUS3FT    'FOPHMJP ,"  #SVOTPO ,-  "WJTIBJ&MJOFS 4  4UPOF #"  ,BQBEJB #+ BOE #BSBN 5;   &OEVSJOH  IBOEMJOHFWPLFE FOIBODFNFOU PG IJQQPDBNQBM NFNPSZ GVODUJPO BOEHMVDPDPSUJDPJESFDFQUPSFYQSFTTJPOJOWPMWFTBDUJWBUJPOPGUIFDPSUJDPUSPQJOSFMFBTJOH GBDUPSUZQFSFDFQUPS&OEPDSJOPMPHZ    'SBODJT%%BOE.FBOFZ.+  .BUFSOBMDBSFBOEUIFEFWFMPQNFOUPGTUSFTTSFTQPOTFT $VSS0QJO/FVSPCJPM    (FTJOH "  #JMBOH#MFVFM "  %SPTUF 4,  -JOUIPSTU "$  )PMTCPFS ' BOE 3FVM +.   1TZDIPMPHJDBMTUSFTTJODSFBTFTIJQQPDBNQBMNJOFSBMPDPSUJDPJESFDFQUPSMFWFMTJOWPMWFNFOU PGDPSUJDPUSPQJOSFMFBTJOHIPSNPOF+/FVSPTDJ    (VOOBS.3  *OUFHSBUJOHOFVSPTDJFODFBOEQTZDIPMPHJDBMBQQSPBDIFTJOUIFTUVEZ PGFBSMZFYQFSJFODFT"OO/:"DBE4DJ  (VOOBS.3BOE%PO[FMMB#  4PDJBMSFHVMBUJPOPGUIFDPSUJTPMMFWFMTJOFBSMZIVNBO EFWFMPQNFOU1TZDIPOFVSPFOEPDSJOPMPHZ    )FJN$ /FXQPSU%+ #POTBMM3 .JMMFS")BOE/FNFSPĒ$#  "MUFSFEQJUVJUBSZ BESFOBM BYJT SFTQPOTFT UP QSPWPDBUJWF DIBMMFOHF UFTUT JO BEVMU TVSWJWPST PG DIJMEIPPE BCVTF"N+1TZDIJBUSZ    )PGFS."  &BSMZSFMBUJPOTIJQTBTSFHVMBUPSTPGJOGBOUQIZTJPMPHZBOECFIBWJPS"DUB 1BFEJBUS4VQQM  ,JTIJ5BOE&MNRVJTU+,  #PEZXFJHIUJTSFHVMBUFECZUIFCSBJOBMJOLCFUXFFO GFFEJOHBOEFNPUJPO.PM1TZDIJBUSZ    -BEE$0 )VPU3- ѮSJWJLSBNBO,7 /FNFSPĒ$# .FBOFZ.+BOE1MPUTLZ1.   -POHUFSNCFIBWJPSBMBOEOFVSPFOEPDSJOFBEBQUBUJPOTUPBEWFSTFFBSMZFYQFSJFODF1SPH #SBJO3FT  -FWJOF4  ѮFPOUPHFOZPGUIFIZQPUIBMBNJDQJUVJUBSZBESFOBMBYJTѮFJOëVFODF PGNBUFSOBMGBDUPST"OO/:"DBE4DJ  -FWJOF 4   1SJNBSZ TPDJBM SFMBUJPOTIJQT JOëVFODF UIF EFWFMPQNFOU PG UIF IZQPUIBMBNJDQJUVJUBSZBESFOBMBYJTJOUIFSBU1IZTJPM#FIBW    -FWJOF4 )VDIUPO%. 8JFOFS4(BOE3PTFOGFME1  5JNFDPVSTFPGUIFFĒFDUPG NBUFSOBMEFQSJWBUJPOPOUIFIZQPUIBMBNJDQJUVJUBSZBESFOBMBYJTJOUIFJOGBOUSBU%FW 1TZDIPCJPM  .

(31) Chapter 2   -JV% %JPSJP+ %BZ+$ 'SBODJT%%BOE.FBOFZ.+  .BUFSOBMDBSF IJQQPDBNQBM TZOBQUPHFOFTJTBOEDPHOJUJWFEFWFMPQNFOUJOSBUT/BU/FVSPTDJ     .BD2VFFO (.  3BNBLSJTIOBO ,  3BUOBTJOHBO 3  $IFO # BOE :PVOH -5   %FTJQSBNJOFUSFBUNFOUSFEVDFTUIFMPOHUFSNCFIBWJPVSBMBOEOFVSPDIFNJDBMTFRVFMBF PGFBSMZMJGFNBUFSOBMTFQBSBUJPO*OU+/FVSPQTZDIPQIBSNBDPM     .BDSJ4 .BTPO(+BOE8VSCFM)  %JTTPDJBUJPOJOUIFFĒFDUTPGOFPOBUBMNBUFSOBM TFQBSBUJPOTPONBUFSOBMDBSFBOEUIFPĒ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ĒFDUVQPOBEVMUBESFOBMDPSUJDBM .

(32) $IBQUFS.  .   .           . . SFTQPOTFUPTUSFTTBOEBESFOBMBOEPWBSJBODPNQFOTBUPSZIZQFSUSPQIZ&OEPDSJOPMPHZ     4DIBQJSP4 (FMMFS&BOE&JEVTPO4  /FPOBUBMBESFOBMDPSUJDBMSFTQPOTFUPTUSFTT BOEWBTPQSFTTJO1SPD4PD&YQ#JPM.FE  4DINJEU .7  %FVTTJOH +.  0JU[M .4  0IM '  -FWJOF 4  8VSTU 8  )PMTCPFS '  .VMMFS .# BOE EF ,MPFU &3   %JĒFSFOUJBM EJTJOIJCJUJPO PG UIF OFPOBUBM IZQPUIBMBNJD QJUVJUBSZBESFOBMBYJTJOCSBJOTQFDJêD$3)SFDFQUPSLOPDLPVUNJDF&VS+/FVSPTDJ     4DINJEU.7 &OUIPWFO- WBOEFS.BSL. -FWJOF4 EF,MPFU&3BOE0JU[M.4   ѮFQPTUOBUBMEFWFMPQNFOUPGUIFIZQPUIBMBNJDQJUVJUBSZBESFOBMBYJTJOUIFNPVTF*OU +%FW/FVSPTDJ    4DINJEU.7 &OUIPWFO- WBO8PF[JL+) -FWJOF4 EF,MPFU&3BOE0JU[M.4   Ѯ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ѮF)1"TZTUFNEVSJOHUIF QPTUOBUBMEFWFMPQNFOUPG$%NJDFBOEUIFFĒFDUTPGNBUFSOBMEFQSJWBUJPO#SBJO3FT %FW#SBJO3FT    4NPUIFSNBO81 .FOEP[B41BOE-FWJOF4  0OUPHFOFUJDDIBOHFTJOQVQFMJDJUFE NBUFSOBMQJUVJUBSZBESFOBMBDUJWJUZQVQBHFBOETUBHFPGMBDUBUJPOFĒFDUT%FW1TZDIPCJPM     4UBOUPO.& (VUJFSSF[:3BOE-FWJOF4  .BUFSOBMEFQSJWBUJPOQPUFOUJBUFTQJUVJUBSZ BESFOBMTUSFTTSFTQPOTFTJOJOGBOUSBUT#FIBW/FVSPTDJ    WBO0FST)+ EF,MPFU&3 8IFMBO5BOE-FWJOF4  .BUFSOBMEFQSJWBUJPOFĒFDUPO UIFJOGBOUTOFVSBMTUSFTTNBSLFSTJTSFWFSTFECZUBDUJMFTUJNVMBUJPOBOEGFFEJOHCVUOPUCZ TVQQSFTTJOHDPSUJDPTUFSPOF+/FVSPTDJ    7B[RVF[ %.   4USFTT BOE UIF EFWFMPQJOH MJNCJDIZQPUIBMBNJDQJUVJUBSZBESFOBM BYJT1TZDIPOFVSPFOEPDSJOPMPHZ    7FOFSPTJ "  $JSVMMJ '  $BQPOF ' BOE "MMFWB &   1SPMPOHFE QFSJOBUBM ";5 BENJOJTUSBUJPOBOEFBSMZNBUFSOBMTFQBSBUJPOFĒFDUTPOTPDJBMBOEFNPUJPOBMCFIBWJPVS PGQFSJBEPMFTDFOUNJDF1IBSNBDPM#JPDIFN#FIBW    8BMLFS$% 1FSSJO. 7BMF8BOE3JWJFS$  0OUPHFOZPGUIFTUSFTTSFTQPOTFJOUIF SBUSPMFPGUIFQJUVJUBSZBOEUIFIZQPUIBMBNVT&OEPDSJOPMPHZ    8FBWFS*$ $FSWPOJ/ $IBNQBHOF'" %"MFTTJP"$ 4IBSNB4 4FDLM+3 %ZNPW4 4[ZG .BOE.FBOFZ.+  &QJHFOFUJDQSPHSBNNJOHCZNBUFSOBMCFIBWJPS/BU/FVSPTDJ     8PSLFM+0 0JU[M.4 -FEFCPFS"BOEEF,MPFU&3  ѮF#SPXO/PSXBZSBUEJTQMBZT FOIBODFETUSFTTJOEVDFE"$5)SFBDUJWJUZBUEBZBѫFSINBUFSOBMEFQSJWBUJPOBU EBZ#SBJO3FT%FW#SBJO3FT    ;IBOH-9 -FWJOF4 %FOU(8 ;IBO: 9JOH( 0LJNPUP%, ,BUIMFFO(. 1PTU3. BOE4NJUI."  .BUFSOBMEFQSJWBUJPOJODSFBTFTDFMMEFBUIJOUIFJOGBOUSBUCSBJO #SBJO3FT%FW#SBJO3FT  .

(33)

(34)

(35)

Referenties

GERELATEERDE DOCUMENTEN

License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden. Downloaded

Chapter 1 ZQPUIFTFTBOEBQQSPBDIFT 1BSU*i3FQFBUFENBUFSOBMTFQBSBUJPOTuѮFEBUBEFTDSJCFEJOTFDUJPOTBOEIBWFMFE

" NBJO FĒFDU XBT PCTFSWFE PG USFBUNFOU ' 1 BOE JOKFDUJPO ' 1 BT XFMM BT BO JOUFSBDUJPO CFUXFFO USFBUNFOU BOE JOKFDUJPO ' 1 JOEJDBUJOH UIBU UIF FĒFDU PG JOKFDUJPO

%JTDVTTJPO $% NJDF SFBEJMZ MFBSOFE UIJT TQBUJBM OBWJHBUJPO UBTL JOEJDBUFE CZ UIF EFDSFBTFE MBUFODZ BOE EJTUBODF TXBN UP MPDBUF UIF TVCNFSHFE QMBUGPSN .BUFSOBM EFQSJWBUJPO EJE

"CTUSBDU .BUFSOBMEFQSJWBUJPO BTFQBSBUJPOPGNPUIFSBOEQVQTGPSIPVSTJOUIFêSTUXFFLTPGMJGF IBTMPOHMBTUJOHDPOTFRVFODFTGPSUIFHMVDPDPSUJDPJETUSFTTTZTUFNѮFTFFĒFDUTBSFLOPXOUP EFQFOE PO UIF BHF

$IBQUFS 3N3/"XBTBSSFTUFEPOEBZ"MUIPVHI 3N3/"FYQSFTTJPOHSBEVBMMZJODSFBTFEBHBJO JU SFNBJOFECFIJOEUIFMFWFMTNFBTVSFEJODPOUSPMBOJNBMTVOUJMBUMFBTUQOE*OFBSMZBEPMFTDFODF QOE 3 N3/"

*OTQJUFPGUIJTBEBQUBUJPO UIF1"BYJTSFNBJOFESFTQPOTJWFBOEUIFDPSUJDPTUFSPOFTFDSFUJPO CFDBNFFWFOSFMBUJWFMZNPSFTFOTJUJTFEUPUIFFĒFDUTPGOPWFMUZFYQPTVSFѮJTêOEJOHJOEJDBUFT UIBU UIF

NBUFSOBM BCTFODF XBT HSBEVBMMZ FMJNJOBUFE XIFO UIF NBUFSOBM TFQBSBUJPOT XFSF SFQFBUFE UIF OFYUUXPEBZT%FTQJUFUIFBCTFODFPGBO1"BYJTSFTQPOTFUPUIFUIJSENBUFSOBMTFQBSBUJPO