Dopaminergie Modulation of

It rain aging involves rrurofunctiorul, ncurmmtomical, ard lJ ncurochcmical charryes, and thc dynamic inEractions bctwcen thcse lewh (see tlbcza, Nybcrg, and Part, 2005; Lindenberger, Li, and Bickrnan,20(b for rccant rariors). Therc arc about 100 billion nerve cclls in the human brain and eadr of thce rrurons communicatcs with at lcast l,(tr0 other rrurons via synaptic nrchanisrns. Owr 99h of all sympses in thc brain usc rrurochcmical tnngnissions. This chapter addrcsscs age-rdatcd ncurochemical dranges that afFct rruronal signal trarsduction. We focus specifcally on age-relatcd impairmcnt in dopamine (DA) s)'scms and their rehtiomhips to co8nitiw dcficits latcr in lift . Other neirrotransmittcr systems-most rrotably rety'choline, mrepincphrine, scrotonin, and glutamae-aho undcrgo alterations during thc aduh life coursc (sce Morgan ard May, t990; Scgovia a al, 2(X) l for rwiavs). Thus hr, howevrr, the DA qrstems haw attractcd thc most attention and thcrc is mounting evidcnce that DA is a kcy neurotrarsmittcr in thc context ofcognitive aging. Molccuhr imaging mahods 6r assessing age-rclatcd dcclinc in preard post-synapic marken of 0re dopaminergic a)BEms, as *tll as more recant gcnomic imaging multimodal imagin6, ard computational ncuroscicrrc approaches to invctigate how dopamincrgic modulation affects cognitivc qing wil bc particularly highlightcd herc. It was only a halfcentury ato that DA was discovcred as an in&pendcnt trarumitter in the ncrvous system, as opposcd to a precursor of other transmitters (sce Bjiirklurd and Dunncft, 2OO7 for review), The dopamincrgic slntems have, however, alrcady bcen widely studied in the contert of aging researdr, owing mainly to (a) the number of rrell-charactirized biomarkcrs for their preard post-synapti< comporrnts, (b) the markcd age-rdated dccrcments observe4 and (c) broad invohrcment of DA in a wi& range of cognitive furrtions and Parkirson's discasc. ln the following section, we first dcscribe the major DA systems in the human brain and methods for imaging thce systcms, Thcn we review evidcncc for DA's role in cognition and the relation*rip bctyrcen age-related &clincs in DA systems and cognitive aging. In thc last scction, r.rr highlight emcrgnt thcmcs ard mvel approrhes that arc amenablc for investigatirg dopaminergic modulation in the aging brain and its furrtionalconsequcncc. Although this chapter focrscs on DA systems, age-related changes in other transrnitter systcms arc likdy to also interact with dopaminergic sFtcms to affect cognitive functions. Outstanding issues rcgarding other transmittcr systems rhat are likely to interact with dopaminc in affcting cognitive furxtions will bc disctsscd as well.