Anais da AcademiaBrasileira de Ci6ncias- Responseof the brain to e... http://www.scielo.br/scielo.php?pid=SOO01-376520O1O00200006&s... *{Il1t1*3-****s, at"ti,:le::Pa;t'r ----*-*-l S J ', "#.,rc,*u* Anaisda AcademiaBrasileira de Ci€ncias Print versionI55N 0001-3765 .it1 customservices An. Acad. Bras" Ci6nc. v*i.73 n*.3 Ki* de.Ianeirc Jume?S*1 % nn"l" in pdfformat d*i: i*.1590l5BAAL-376520010002*0S06 .:#i; nrti"t" in xmlformat 'ffi,| arrclereferences Responseof the Brain to Enrichment: to citethis article HlHow .$ii nccessstatistics MARIAN C. DIAMOND ffi cit"oby sciELo :W,i si^iLr" inSciELo Departmentof Integrative Biology,3060 Valley Life SciencesBuilding Automatictranslation University of California,Berkeley, CA94720, USA -1.1 sno* se antichighlights Manuscript received on March 5,2001; accepted for publication on March W} tl,ilrrlt 12, 2001; Senathis article by e-mail presented by LENYA. CAVALCANTE ABSTRACT Before1960, the brainwas considered by scientiststo be immutable,subject only to geneticcontrol. In the earlysixties, however, investigators were seriously speculating that environmentalinfluences might be capableof alteringbrain structure. By 1964,two researchlaboratories proved that the morphologyand chemistryor physiologyof the braincould be experientiallyaltered (Bennett et al. 1964,Hubel and Wiesel '1965). Sincethen, the capacityof the brainto respondto environmentalinput, specifically "enrichment," has becomean acceptedfact amongneuroscientists, educators and others.In fact,the demonstrationthat environmentalenrichment can modifystructural components of the rat brainat any age alteredprevailing presumptionsabout the brain'splasticity (Diamond et al. 1964,Diamond 19BB). The cerebralcortex, the areaassociated with highercognitive processing, is more receptivethan other parts of the brainto environmentalenrichment. The messageis clear:Although the brainpossesses a relatively constantmacrostructural organization, the ever-changingcerebral cortex, with its complexmicroarchitecture of unknownpotential, is powerfullyshaped by experiencesbefore birth, during youth and, in fact,throughout life.It is essentialto notethat enrichmenteffects on the brainhave consequences on behavior.Parents, educators,policy makers, and individualscan all benefitfrom suchknowledge. Key words: enrichment,cerebral cortex, hippocampus, aging, adult neurogenesis, dendrites. INTRODUCTION 1of10 1122110l2:15 PM Anais da AcademiaBrasileira de Ci€ncias- Responseof the brain to e... http:/hvrvw.scielo.br/scielo.php?pid=S0001-37652001000200006&s... Canexperience produce measurable changes in the braln?The hypothesisthat changesoccur in brain morphologyas a resultof experienceis an old one.In 1815Spurzheim asked whether organ size could be increasedby exercise.He repoftedthat the brainas well as musclescould increase with exercise"because the bloodis carriedin greaterabundance to the partswhich are excitedand nutritionis performedby the blood."ln t874 CharlesDarwin mentioned that the brainsof domesticrabbits were considerably reduced in bulkin comparisonwith thosefrom the wild because,as he concluded,these animals did not exerttheir intellect,instincts, and sensesas muchas did animalsin the wild.However, it was not untilthe 1960s,that the first controlledstudies in animalsdemonstrated that enrichingthe environmentalcondition in whichthey wereconfined could alter both the chemistryand anatomyof the cerebralcortex and, in turn, improvethe animals'memory and learningability. In theseearly experiments only the brainsof younganimals were studied. Although many were impressed to learnthat the cerebralcoftex could increase its thicknessin responseto enrichedliving conditions, they raisedthe questionabout whether enrichment might similarly affect older animals. Once middle-aged rats brainsshowed positive responses to enrichment,the nextstep was to experimentwith very old animals. Onceagain, increases in corticalthickness were found. It then becameimportant to discoverwhat was responsibiefor thesechanges. Onestep at a time,the levelof morphologicalchanges - from neuronalsoma size, to numberand lengthof dendrites,to typesand numbersof dendriticspines, to synapticthickening, to capillarydiameter, and to glial typesand numbers- wasexamined. Age, gender, duration of exposure,etc. were critical variables that had to be tested in new experiments. Mostof the basicdata reportedon the enrichmentparadigm and its impacton brainand behaviorhave accumulatedthrough studies on the rat. Effectsof enrichedand impoverishedenvironments on the nerve cellsand their neurotransmittersin the cerebralcortex have now beengeneralized to severalmammalian and avianspecies (Rosenzweig and Bennett1996). Some corroborating studies mentioned herein involved cats and monkeys,as wellas isolatedstudies in humansubjects. For example, Jacobs et al. (1993)using an isolatedportion of the humancerebral cortex responsible for word understanding,Wernicke's area, compared the effectsof enrichmentin tissuefrom deceasedindividuals who had hada collegeeducation and from those who had hadonly a highschool education. They demonstrated that the nervecells in the college-educated showedmore dendritesthan those in the latter. (Tissuewas obtainedfrom the Veteran'sHospital in west Los Angeles.)Experiments on humantissue frequently support the dataobtained from studiesin the rat, and, in turn, benefitfrom theseanimal studies. We can nowsafely say that the basicconcept of brainchanges in responseto enrichmenthold true for a widevariety of animalsand for humans. THE EFFECTSOF ENRICHMENTON THE CEREBRALCORTEX What do we meanby "enrichment"for the rats who haveserved as the animalof choicefor most of these studies?Thirty six Long-Evansrats were sorted into three experimental conditions using 12 animalsin each group:1) enriched2) standardor 3) impoverishedenvironments. All animalshad free accessto foodand waterand similarlighting conditions. Eventually, it wasdetermined that animalsmaintained in their respectiveenvironments from the age of 30 daysto 60 days developedthe most extensivecerebral cortical changes.For the enrichedenvironment, the 12 animalslived together in a largecage ( 70 x 70 x 46 cm) and wereprovided 5-6 objectsto exploreand climbupon (e.9., wheels, ladders, small mazes). The objectswere changedtwo to threetimes a weekto providenewness and challenge;the frequentreplacement of objectsis an essentialcomponent of the enrichedcondition. The combination of "friends"and "toys"was established earlyon by Krechas vitalto qualifythe experientialenvironment as "enriched."(Krech et al. 1960).Forthe standardenvironment, the animalswere housed 3 to a smallcage ( 20 x 20 x 32 cm) with no exploratory objects.For the impoverishedenvironment, one animal remained alone in a smallcage with no exploratory objects. The numbersof animalsplaced in theseseparate conditions were based on the mannerin whichthe routine housingwas established in the rat colony.Three rats in a cagehas been considered standard for all experimentalwork overthe decades.Since prior to theseexperiments no one haddesigned studies to examinebrain changes in responseto differentenvironmental conditions, the decisionsabout what represented"impoverishment" and what represented"enrichment" was morearbitrarily than scientifically 2ofl0 412211012:15PM Anais da AcademiaBrasileira de Ci6ncias- Responseof the brain to e... http://lvlvw.scielo.brlscielo.php?pid=S0001-3765200100O200006&s... reasoneo. After 30 days in their respectiveenvironments/ all animalswere anesthetizedbefore the brainswere removed for comparisonamong the threegroups. Twenty micrometer frozen sections were cut and stained,and the thicknessof the frontal,parietal and occipitalcortices were measured. Results indicated clearly that the cortexfrom the enrichedgroup had increasedin thicknesscompared with that livingin standardconditions, whereas,the brainsfrom the impoverishedgroup decreased compared to the standard.Because the nerve cellswere farther apart in the enrichedvs. the impoverishedbrains, it wasthought that the major componentof the brainchanges due to enrichmenthad to do with alterationsin the dendriticbranching. With moredetailed studies, the corticalthickness increases were found to be due to severalfactors, including increasednerve cell size, number and lengthof dendrites,dendritic spines, and lengthof postsynaptic thickeningas measuredon electronmicroscopic pictures of synapses.(Diamond et al. 1964and 19BB). In the initialexperiments designed to explorethe impactof an enrichedenvironment on the brainof post-weanedrats, only enriched and impoverishedgroups were used. Rats were maintained in their respectiveenvironments from 25 to 105 days of age becausethere were no availabledata on how long it wouldtake to createchemical or structuralchanges in the cortex.Chemical and anatomicalmeasurements takenfrom theseanimals showed significant differences between the two groups- in corticalthickness, corticalweight, acetylcholinesterase, cholinesterase, protein and hexokinaselevels, (Bennett et al. 1964, Diamondet al. 1964).In theseinitial experiments, however, it was not clearif the changeswere due to enrichmentor impoverishmentbecause there were no standardconditions established as controls. Nonetheless,the differencesin corticalthickness with this 80-dayexposure to the two environmental conditionswere not as greatas duringthe 30-dayexposure. Consequently, in subsequentexperiments, the periodof exposureto the experimentalconditions was reducedfrom 80 daysto 30 days,then 15 days,7 daysand finally