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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,, , aging, adult , .

INTRODUCTION

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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 .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 daysdeveloped the 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

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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 .(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 daysof 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, , 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 to 4 days.At eachof theseintervals, animals from the enrichedenvironment showed increasesin cerebralcortical thickness in someareas but not in others.For example, in the maleanimals exposedfor B0 daysto enrichedconditions, the somatosensorycortex did not showsignificant changes, whereasmale animals exposed for 30 daysdid developsignificant differences in the somatosensorycortex. The occipitalcortex showed significant changes for boththe B0- and the 30-dayexperiments, but, again,the differenceswere greater at 30 daysthan at B0 days.It is possiblethat the longerexposure served to increasecortical thickness in the earlydays of enrichmentbut that overtime the environmentalcondition becamemonotonous and this effectdecreased. In laterexperiments the experimentalconditions were modifiedto try to establishwhat the major factorswere that createdthe observedcortical changes. For example,was the effectassociated with the numberof rats exposedor to the presenceof stimulusobjects? The newconditions included one rat livingalone in the largeenrichment cage with the objectsthat were changedseveral times eachweek. The cortexof these rats did not showa significanteffect of enrichment. Twelverats livingtogether in the largecage without the stimulusobjects did not showas greatan effectas 12 ratsliving with the stimulusobjects. In otherwords, the combinationof socialconditions and frequent exposureto newstimulus objects were necessary for the animalsto gainthe full effectof enrichment.

Establishingwhat constitutes"enrichment" for humanbeings is more problematic.Not onlyare controlled experimentsnot feasible,but no two humanbrains are identical,Individuals differ in theirgenetic backgroundsand environmentalinputs. Furthermore, what is consideredenrichment for one individualmay be quite differentfor another.Yet, as mentionedearlier, the enrichmenteffect was evidentin Wernicke'sarea from measurementsof the amountof dendriticbranching in braintissue from college-educatedindividuals versusthat from highschool-educated people. The basicfinding of dendriticgrowth in responseto environmentalstimulation appears in all brainsstudied to date.It wouldappear that newnessand challenge are importantfor the humancortex as wellas for that of animals.

INDEPENDET'ITVARIABLES: AGE AND GENDER

Amongthe manyvariables researchers must consider as they seekto understandand accuratelyinterpret the effectsof enrichmenton the brain,age and genderare importantconsiderations. Enrichment has been shownto enhancemany aspectsof corticalstructure at any age - from prenatalto extremelyold rats (904 daysof age).The amount of changevaries with the ageof the animal.For example, when a 3O-day-oldrat is put in an enrichedenvironment for four days,the effectsare not as pronouncedas they are in the 60-day-old-ratmaintained in enrichedconditions for four days.Is four daystoo shorta time for the very

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younganimal to adjustand benefitfrom enrichment?A younganimal maintained for 30 daysin an impoverishedenvironment shows reduced morphological development of its cortexwhen compared to that of an adultanimal maintained in impoverishedconditions for 30 days.In fuftherage-related experiments, anothercomponent was addedto the enrichmentconditions of old rats.Despite significant increases in the lengthof the dendritesin the brainsof 600-day-oldrats that had beenplaced in an enrichedenvironment for 30 days(600 to 630 days),several of the old ratsin this populationdied.

To determinewhether the enrichmentconditions could be modifiedto extendthe animals'life span, the investigatorsadded a newcomponent: hand-holding the ratseach day for severalminutes while the cages werecleaned. In an attemptto increasethe lifespan of the rats,rats were placed three to a cageafter weaningat 25 daysof age,and maintainedin thesestandard conditions until they reached766 days,at whichtime halfwent intoenriched conditions until they reached904 daysof age and halfstayed in the standardconditions. The onlyvariable added was the dailyhand-holding of the ratsas they aged.Is it possiblethat handlingthe rats hadextended their lifespan? Indeed, many investigatorshave been amazed thattheserats survived to 904 daysof age.The 904 day-oldrats in enrichedconditions developed a cortex significantlythicker than the cortexof rats livingin the standardconditions (Diamond 1988). These experimentsoffered support to the thesisthat the cerebralcortex is capableof respondingpositively to an enrichedenvironment at any age (Seefrq- 1).

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Experimentscomparing the effectsof enrichmenton maleand female are few. Mostenrichment studieshave been carried out on malebrain to avoidthe compoundingfactors associated with the estrous cycle.In one study focusedon gender,the femaleneocortex was found to responddifferently from the male neocortexexposed to the sametype of enrichmentconditions (Diamond 1988). The maleshowed significant changesin corticalthickness in the occipitalcortex, but no significantchanges in the somatosensorycortex. (Althoughthe rightcerebral coftex in the brainof the malerat is thickerthan the left,especially in the visual or occipitalregion, an enrichedenvironment appears to alterboth the rightand left cortexsimilarly.) In the female,the thicknessof the occipitalcortex increased significantly in responseto enrichment,although not as muchas in the male,but the thicknessof the somatosensorycortex increased significantly more in the

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femalethan in the male.In a follow-upexperiment, however, in whichobstacles were piled up in frontof the femalefood cup to providea greaterchallenge to her alreadyenriched environment, the thicknessof the occipitalcortex increased as muchas did that of the malewithout the additionalchallenge.

In rats whosetestes were removedeither at birth or at 30 daysof age beforethe rats were placedin an enrichedenvironment for 30 days,the increasesobserved in cofticalthickness were similar to thoseof their littermateswith intacttestes. (Diamond 1988) These findings suggested that testosteroneis not implicated in the increasesin corticalthickness observed in the brainsof ratsliving in enrichedenvironments. Since sex differenceswere evident in the responsesof the animalsto enrichment,interest was nowfocused on the brainsof pregnantrats, in whichthe concentrationsof sex steroidhormonal concentrations are greatly altered.The brainsof femalerats livingin the enrichedenvironmentfrom 60 to 90 daysand then becoming pregnantand returningto enrichmentuntil 116 daysof agewere compared between nonpregnant and pregnantanimals living in an impoverishedenvironment for the sametime periods.When animals from the two groupswere autopsied at 116days, no significantdifferences in corticalthickness were found. Evidently, pregnancyhas an effecton the cerebralcortex regardless of whetherthe environmentis impoverishedor enriched.

Theseinitial experiments, all of whichwere replicated, clearly indicate gender differences in the brain's responseto enrichment.Having dealt with the independentvariables, we turn to the impactof dependent variablesin the enrichmentparadigm. For these studies, one must lookat: durationof exposure,brain anatomyand chemistry,presence of lesionsor fetal neocorticalgrafts, negativeair ions,stress, physical activityand nutrition,as wellas behavioraleffects. These are discussedin turn below.

Duration:The durationof exposureto the enrichedenvironment is clearlya significantdependent variable that must be factoredinto researchin this area.As shorta periodas 40 minutesof enrichmenthas been foundto producesignificant changes in RNAand in the wet weightof cerebralcortical tissue sampled. One day of enrichmentwas insufficientto producemeasurable changes in corticalthickness, whereas four consecutivedays of exposure(from 60 to 64 daysof age)to an enrichedenvironment did producesignificant increasesin corticalthickness, but only in the visualassociation coftex (area 18) (Diamond19BB). Whenyoung adult rats were exposed to 30 daysof enrichment,however, the entiredorsal cortex, including frontal,parietal and occipitalcortices, increased in thickness.Extending the durationof the stay in enriched conditionsto B0 daysdid not produceany greaterincrease in corticalthickness than that seenat 30 days(in fact,it wasoften even less); however, the longerthe rat remainedin the enrichedconditions, the longerthe cortexretained its increaseddimensions following return to the standardenvironment (Bennett et al. 1974). Whenwe lookedat age-relateddifferences in the contextof durationof stay in the enrichedenvironment, we foundthat old rats( 766 daysof age) placedin enrichedconditions for 138 daysshowed an increasein corticalthickness that wasquite similar to that observedin youngadult rats (60 daysof age)that had lived in enrichedconditions for 30 days.

Anatomicaland chemicalcomponents: Earlyexperiments, and those to followin subsequentyears, again demonstratedsignificant differences in brainchemistry and anatomyassociated with enrichedliving conditions.Anatomical increases include all of the structuralconstituents measured in the cerebralcortex to date,such as corticalthickness (Diamond et al. 1964),nerye cell soma size, nerve cell nuclear size (Diamond 1988),dendritic dimensions (Holloway 1966, Greenough et al.7973),dendritic spines, synaptic size and number(Mollgaard et al. 1971,Black et al. 1990),number of ,capillary diameter (Diamond 1988), dendriticnumber after lesions(McKenzie et al. 1990),and successfultissue grafts, (Mattsson et al. 1997). Chemicalincreases include: total protein,RNA-Io-DNA ratio, cholinesterase-to-acetylcholine ratio, Nerve GrowthFactor mRNA, cyclic AMP, choline acetyltransferase, cortical polyamines, NMDA (N MethylD Aspartate)receptors, and hexokinase,etc.

LesionslAnother variable has to do with the impactof enrichedconditions on purposefullyincurred brain lesions.In a 1990study, 60-day-old rodents were exposed for 30 daysto eitheran enrichedor standard environmenttwo daysafter havingreceived a lesionin the left frontalcortex that createda motor dysfunction in the rightforepaw. Animals living in the enrichedcondition showed significant increases in corticaldendritic branchingin bothhemispheres, the lesionedand the non-lesionedsides, along with a significantreturn of motorfunction in the rightforepaw compared to thoseanimals living in standardconditions (McKenzie et al. 1990).

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Fetal neocortical graft: Similarly,providing an enrichedenvironment to rats that had undergonefetal neocorticalgrafts one week after lesioningwas foundto improvebehaviorally and to reducethe atrophyin the thalamus,a majorstructure beneath the cortexthat suppliesneural input to the cortex(Mattsson et al. L997).The fact that the fetal neocorticalgraft when placedin the lesionedcerebral cortex couldprevent atrophyin the underlyingthalamus as a consequenceof enrichmentis of greatinterest to researchers consideringthe futurepossibility of usingsuch grafts for brain-damagedindividuals.

Air ions: The possibilitythat physicalenvironmental stimuli other than those classically regarded as "sensory"could have an effecton the brainwas tested experimentally by exposingrats living in enrichedor standardenvironments to highconcentrations of negativeair ions,The experimentswere undertakento determinewhether the effectof negativeions on ,the putativesecond messenger cyclic-AMP, and on cyclicGMP in the cerebralcortex, differ depending on whetherthe animalslived in enrichedor standard conditions.Studies demonstrated that rats placedin the enrichedenvironment in the presenceof enhanced negativeair ions(ion density of 1 x 105)showed a significantdecrease in serotonin,an effectnot foundin the brainsof animalsliving in standardconditions (Diamond et al. 1980).Measurements of cyclicAMP decreased as well in the brainsof the animalsliving in the enrichedconditions, but cyclicGMP did not.These results indicatethe importanceof consideringair qualityand atmosphericconditions in determiningthe brain's responseto enrichment.

Stress: The presenceor absenceof stressrepresents yet anothervariable to be taken into considerationin suchstudies, certainly so in any extrapolationof thesefindings to humans,Stress is a majorfactor in contemporary,fast-moving urban life. Crowding, for example,is deemedstressful under conditions where competitionfor spaceor food is likely.Experiments were set up to assessthe effectof crowdingon the brains of ratsmaintained in an enrichedenvironment. To createa conditionin whichcrowding would be experienced as stressful,36 ratswere placed in an enrichmentcage usually housing only 12 rats,and kept therefor 30 days.The resultsindicated that, comparedwith rats livingin standardconditions, the thicknessof the medialoccipital cortex increased significantly whether the enrichmentcage housed 12 or 36 animals, (Diamondet al. 1987).One hypothesis to comefrom this studywas that the animals'interaction with the toys might be divertingtheir attentionor entertainingthem sufficientlyto mitigatethe stressof the crowded condition.

Chronicstress has been reported by Meaneyet al. (1988)to produceexcess glucocorticoids, which are toxic to neurons- especiallythose of the hippocampus.Aged rats are particularlyvulnerable to chronicstress. The investigationsof Meaneyshowed that enrichingthe livingconditions of old rats,or handlingthem in their infancy,helps to preventstress-related hippocampal damage.

It is possiblethat stresscan be producedby increasingthe frequencywith whichthe variousobjects in the enrichmentcage are changed.In all previousstudies, objects had beenreplaced daily or at leastseveral timeseach week. Then the questionwas asked whether increasing the frequencyof changingthe objects wouldfufther increasethe growthof the corticalthickness/ or/ alternatively,would it be experiencedas a stressfactor, given that the animalswere inhibited from interactingwith them in the more leisurelymanner to whichthey wereaccustomed. For these experiments, rats 60 to 90 daysof agefound their objects changedevery hour for threehours on four nightsof eachweek for four consecutiveweeks. Under this regime,the cerebralcortical thickness did not grow significantlycompared to corticesfrom rats whose objectswere changed several times each week for four weeks(Diamond, unpublished.)

Corticosteroids,released under stress, have been shown to reducecortical thickness and futureexperiments would be necessaryto comparedifferences in corticosteroidlevels in animalsexposed to thesediffering conditions.

Behavior:Psychologists have known for a longtime that earlyexperience influences the adultpeformance of an animal.In experimentsin the 1950s(Bingham and Griffiths1952 and Forgaysand Forgays1952) investigatorswere interested in determininghow muchexperience in complexenvironments was necessary to producea highlyintelligent adult animal and when,specifically, during early life these experiences had to occur.These studies showed that all of the animalsmaintained in enrichedconditions were betterproblem solversthan those with no enrichment;however, in someother occasions, using other tests, enriched rats did not performsignificantly better than controls.

One of the most robusteffects of environmentalenrichment on the behaviorof rats appearsin the areasof

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learningand memory.Investigators (York et al. 1989and Kempermannet al 7997)studying the effectsof enrichmentin the rat brainhave reported that new nervecells develop in the adultdentate gyrus, an area dealingwith recentmemory processing, In the Yorkexperiments the ratswere 60 to 90 daysof age (truly adultanimals) during the enrichmentexperience, whereas in the Kempermannexperiments the micewere 2tto 40 daysof age.These finding are significantbecause neurogenesis had not previouslybeen found in the cerebralcortex of the mammalianadult. Earlier studies had found that enrichedenvironments stimulare the growthof dendritesin the dentategyrus, and only in femalerats, (Juraska et al. 1985).

PhysicalActivity: Onecomponent of enrichmentis the physicalexercise involved in the animals'having to moveabout the cage,interacting with and climbingupon the novelobjects. These activities appear to influencethe motorcortex as wellas the hippocampus.Olsson et al. (1994)showed that ratsliving in enrichedenvironments at 50 daysof ageshowed higher expression of the gene-encodingglucocorticoid receptorsand inductionof genesfor NerveGrowth Factors In the hippocampus.

Nutrition: Nutritionis clearlyan importantvariable to considerin all studiesdealing with brainand behavior. Environmentalenrichment and impoverishmenthave pronounced effects on nutritionallydeficient animals. Onestudy compared the effectsof environmentalenrichment on the offspringof motherrats livingon protein-richor protein-deficientdiets during (Carughi et al. 1990).The protein-richdiet proved beneficialfor the healthydevelopment of the cerebralcortical dendrites in youngrats and evenmore so when combinedwith an enrichedenvironment.

The cerebralcortical dendrites in rat pupsfrom motherswith a protein-deficientdiet were significantlyless well developedthan those of their counterpafts,but, of greaterimportance, the coftex from the protein-deficientanimals did not significantlyincrease with enrichment.On the other hand,when protein-deficientpups were fed a protein-richdiet and maintainedin an enrichedenvironment during their early postnatallife, corticaldevelopment improved almost to the levelseen in rat pupsfrom motherson a high-proteindiet duringpregnancy followed by postnatalenrichment. These data are very encouraging, becausethey suggestthe possibilityof makingup for lost braingrowth during pregnancy by enrichingboth the diet andthe environmentalconditions during the postnatalperiod.

Anotherdietary factor significant to optimalbrain function is glucose.The braindepends almost exclusively on glucosefor its energy.Synapses use a greatdeal of energyand glucosesupplies this energy.Although we knowthat differentparts of the brainuse glucoseat differentrates, to learnwhich of 30 discretebrain regionswere most active in adultrats placed in enrichedliving conditions from 57 to 87 daysof age,we studiedtheir radioactiveglucose uptake during this 30-dayperiod and comparedit with that of rats raisedin standardconditions (Diamond 1988). Again, the cerebralcortex showed the greatestdifferences between enrichedand nonenrichedgroups, but, surprisingly,of the two groups,glucose uptake was lowerin rats maintainedin enrichedconditions. We concludedfrom this findingthat glucoseuptake is moreefficient in the brainof animalsliving in enrichedenvironments. Out of the 30 areasof the brainmeasured, including the cottex,only one area showed significantly greaterglucose uptake in the enrichedanimals: the corpus callosum,specifically, the largemass of axonsconnecting the nervecells between the two cerebral hemispheres.Could the axonsforming the corpuscallosum from the nervecells in the cerebralcortex be more activethan the nervecell bodiesfrom whichthey arise?Yet the right and left cerebralcortices show comparablecortical thickness increases with enrichmentdue to the effectson dendriticbranching, but now the data showthat the ratesof glucoseutilization in both the frontal and parietalcoftices were 1370lower rn the enrichedrats than in the standardcontrol rats, a paradoxto be untangledin the future.

Methodological issues associated with enrichment research in humans: Of the vast numberof animal studiesthat yieldresults of interestto humanresearch, studies on the impactof an enrichedenvironment on braindevelopment and behaviorcan be of enormousinterest to humans.Despite similarities in somekey respectsbetween the brainof the rat and othermammals, replicating or extrapolatingfrom anatomicaland chemicalstudies conducted in animalsis fraughtwith difficulty,for obviousreasons. Not only is it not presentlypossible to controlall of the experimentalvariables at work in humans,but the diversityand complexityof humanexperience militates against designing experiences comparable to thoseused with lower animals.

Nevertheless,these studies and what few humanstudies have been done, suggest that thereare measurablebenefits to enrichingan individual'senvironment in whateverterms that individualperceives his immediateenvironment as enriched.At the very least,this work indicatesthat thereare manyopportunities

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for enhancingbrain activity and behaviorat all ages,and that they can havepronounced effects throughout the lifesoan.

RESUMO

Antesde 1960,os cientistasconsideravam o enc6falo como imutdvel, sujeito apenas ao controlegen6tico. Entretanto,no iniciodos anos 60, algunspesquisadores especulavam seriamente que influGnciasambientais podiamser capazesde alterara estruturacerebral. Por volta de 1964,dois laborat6rios de pesquisa demonstraramque a morfologiae a quimicaou a fisiologiado c6rebropoderia ser modificadapela experiGncia (Bennettet al. 1964,Hubel e Wiesel1965). Desde ent6o, a capacidadedo c6rebroa responderpara respondera insumosambientais, especificamente ao "enriquecimento",tornou-se um fato aceitopor neurocientistas,educadores e outros.De fato, a demonstragSode que o enriquecimentoambiente pode modificarcomponentes estruturais do c6rebrode rato,em qualqueridade, alterou suposig6es prevalentes a respeitoda plasticidadecerebral (Diamond et al. 1964,Diamond 19BB). O c6rtexcerebral, a Sreaassociada com o processamentocognitivo superior, 6 mais receptivodo que outras partesdo enc6faloao enriquecimentoambiental. A mensagem6 clara:embora o enc6falopossua uma organizaESomacro-estrutural relativamente constante, o sempre-mutdvelc6rtex cerebral, com sua microarquiteturacomplexa de potencialdesconhecido, 6 fortemente moldado pelas experiOncias antes do nascimento,durante a juventudee, em verdade,ao longode todaa vida.E essencialque se noteque os efeitosdo enriquecimentosobre o enctifalot6m consequ6nciasno comportamento.Pais, educadores, geradoresde politicase quaisquerindividuos podem todos se beneficiarde tal conhecimento. Palavras-chave:enriquecimento, c6rtex cerebral, hipocampo, envelhecimento, neurogOnese em adultos, dendritos.

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