Experience and Brain Development

WiUiam T. Greenough, James E. Black, andChristopher S. WallaceUniversity of Illinois at Urbana-Champaign

GREENOUGH, WILLIAM T.; BLACK, JAMES E.; and WALLACE, GHRISTOPHER S. Experience and BrainDevelopment. GHILD DEVELOPMENT, 1987, 58, 539-559. This article considers how experience caninfluence the developing and mature brain and proposes a new categorization scheme based uponthe type of information stored and the brain mechanisms that appear to be involved in storing it. Inthis scheme, experience-expectant infonnation storage refers to incorporation of environmental in-formation tliat is ubiquitous in the environment and common to all species members, such as thebasic elements of pattem perception. Experience-expectant processes appear to have evolved as aneural preparation for incorporating speciBc infonnation: in many sensory systems, synaptic connec-tions between nerve cells are overproduced, and a subsequent selection process occurs in whichaspects of sensory experience determine the pattem of connections that remains. Experience-dependent infonnation storage refers to incorporation of environmental information that is idiosyn-cratic, or unique to the individual, such as leaming about one's specific physical environment orvocabulary. The neural basis of experience-dependent processes appears to involve active formationof new synaptic connections in response to tfie events providing the information to be stored.Although these processes probably do not occur entirely independently of one another in develop-ment, the categories oflfer a new view more in accord with neural mechanisms than were terms like"critical" or "sensitive period."

What is die Meaning of Infancy? What isthe meaning of the fact that man is bominto the world more helpless than anyother creature, and needs for a muchlonger season than any other living thingthe tender care and wise counsel of hiselders? [John Fiske, 1883/1909, p. 1]

The extended period of infancy reflectsthe importance of incorporating enormousamounts of infonnation into the brain. It hasbeen estimated that, even within the muchsmaller brain of the rat, perhaps a quarter ofamillion connections between nerve cells areformed each second during the first month ofpostnatal development (Schuz, 1978). Theseconnections, at least those that persist, com-prise the combination of intrinsic and ex-periential information, recorded in neuralcircuitry, upon which behavior is based.Although research has demonstrated substan-tial effects of experience on brain connec-tions, we do not yet understand just howthe infant's brain is specialized to organizeand incorporate experience, or the ways inwhich the infent may program its own experi-ence. However, biological research using ani-

mals has helped outline basic mechanismswhereby experience affects the brain, and hasprovided a new view of how the brain mayadapt to different types of experience.

Such studies of animal developmenthave suggested a fundamentally differentview of what have been called "sensitive-period" or "critical-period" phenomena. Thetraditional concept has been likened by Bate-son (1979) to the brief opening of a window,with experience influencing developmentonly while the window is open. A window forvisual development in kittens, for example,might open at the time the eyes first open,and close a few weeks later. Although theterm "sensitive period" is a useful label forsuch a process, it does little to explain theunderlying mechanisms. We propose a newclassification based on the type of infonnationthat is stored and the brain mechanisms usedto store it. This approach allows considerationof the evolutionary origins of a process, itsadaptive value for tbe individual, the re-quired timing and character of experience,and the organism's potentially active role inobtaining appropriate experience for itself.

Preparation of this paper and research not otherwise reported was supported by NIMH 40631,NIMH 35321, NIH RR 07030, PHS 5 T-32EY07005, PHS 5 T-32GM7143, ONR N00014-85-K-0587,the Retirement Research Foundation, the System Development Foundation, and the University ofIllinois Research Board. Requests for reprints should be sent to the first author at the Department ofPsychology, University of Illinois at Urbana-Ghampaign, 603 E. Daniel Street, Champaign, IL61820.

[Child Development, 1987, 58, 539-559. ® 1987 by the Society for Research in Child Development, Inc.All rights reserved. 0009-3920/87/5803-0017901.00]

540 Child Development

We propose that manmialian brain devel-opment relies upon two different categories ofplasticity for the storage of environmentallyoriginating information. The first of theseprobably underlies many sensitive- or critical-period phenomena. This process, which weterm experience expectant, is designed toutilize the sort of environmental informationthat is ubiquitous and has been so fhrou^outmuch of the evolutionary history of thespecies. Since the normal environment reli-ably provides all species members witii cer-tain experiences, such as seeing contrast bor-ders, many mammalian species have evolvedneural mechanisms ^ t take fuitvan^ge ofsuch experiences to shape developing sen-sory and motor systems. An important compo-nent of the neural processes underlying expe-rience-expectant information storage a^^arsto be the intrinsically governed generation ofan excess of synaptic connections amongneurons, with experiential input subse-quently determining which of them survive.The second type of plasticity, which we callexperience dependent, is involved in the stor-age of information that is unique to the indi-vidual. Mammals in particular have evolvednervous systems that can take advantage ofsuch information, as of sources of food andhaven, and individual survival depends upcmit to a very great extent. Since such experi-ence will differ in b c ^ timing £uid characteramong individuals, tfie nervous system mustbe ready to incorporate the infonnaticm whenit becomes available. An important aspect ofthe mechanism underlying experience-de-pendent information storey appears to bethe generation of new synaptic connectionsin response to tiie occurrence of a to-be-re-membered event.

in

That tiiere are sensitive periods duringwhich experience maiupulations profoundlyaifect sensory-system development in mam-mals is well known, and this violl be reviewedonly briefly here. For more extensive re-views, the reader is referred to Mitdiell andTimney (1984) or Movshon and Van Sluyters(1981). The vast mf^ority of data regarding ex-perience ^fects on sensory develcqimenthave come from stucUes of ttie visual system.However, to the extent thfd other im^alitieshave been examined, relatively similar resultshave been obtained (Clopton & Winfield,1976; Feng & Rogowski, 1980; Meisami,1975). The visual manipulations range fromtotal pattem deprivation (bilateral eyelid su-

ture or dark rearing) to selective deprivation(e.g., of certain contours or of movement).Monocular deprivation in species with binoc-ularly overlapping visual fields and binoculardepth perception is a special case that will bediscussed separately. Each of these manipula-tions interferes with an experience that other-wise would be common to the young of thespecies.

BehaviorTotal pattem deprivation may occasion-

ally involve interpretatioiml problems, sincedark rearing can disturb endocrine rhythms,parental behavior, and feeding (Eayrs 6f Ire-land, 1950; Mos, 1976) and can damage theretinae of some species (Rsach, Swift, Riesen,& Chow, 1961), and eyelid suture canlengthen the optical axis of the eye, causingnearsi^tedness (Wiesel & Raviola, 1977).NoneAeless, an extensive literature demon-stndies tfiat behavioral deficits resulting fromtotal pattem depriv^on arise primarily fromimpairment of visual infonnation processingby the brain. In rats, for example. Tees (1979)has noted that particular aspects of visual dis-crimin^on tasks, such as the relation amongelements within the stimulus, rather than tBskdifficulty per se (measured as number of trialsrequired for learning), are sensitive indicatorsof visual deprivati<m induced impaimientMoreover, visually deprived rats are not im-paired on similarly complex tasks involvingnonvisual modalities (Tees & Cartwright,1972). A human pE^lel to this process is theimp^red vision of the surgically correctedcongenital cataract patients of Senden (1960).For at least 2 weeks, such psUients could dis-criminate forms such as squares and trianglesonly by counting tl^ir earners. In general, to-tal depriv^on eflfects become less reversibleby later visual expertence with lor^er periodsof depriv^on (Grabtree & Riesen, 19TO; Tim-ney, Mitchell, & Cynader, 1980). This mayresult in part because deprived animals tendincreasingly to rely on nonvisual cues (Fox,1966), but it certainly reflects impairment ofvisual processing ability as well.

PhysiologyDeficits at the neurophysiological level

parallel, and presumably underlie, the behav-ioral impairments. The neurojAysiological def-icits described to date prolably relate moreclosely to differences in acuity tfian to ones incomplex aspects of form and pattem percep-tion—the latter processes having not yet beenunderstood at the neuroj^ysiological level.What have been studied are the stimuli thatbest activate single neurons in the visual sys-tem, recognizing generally that such neurons

Greenough, Black, and Wallace 541

are merely components of a quite com-plicated circuit In kittens at the time the eyesopen, somewhat less than half of primary vi-sual cortex neurons respond selectively to theorientation or direction of movement of astimulus (Blakemore & Van Sluyters, 1975;Buisseret & Imbert, 1976). Over severalweeks in normal light, virtually all cells gainorientation sensitivity, and there is a generaltendency for cells to become much moreselective to specific orientations as well. Inthe absence of patterned visual stimulation,visual cortex neurons gradually lose respon-siveness to stimulus orientation. As with be-havior, the degree to which recovery towardnonnal physiological responsiveness can beachieved with exposure to patterned stimula-tion declines as deprivation is prolonged (Cy-nader, Berman, & Hein, 1976). Moreover, therecovered animal, if it has bincwularly over-lapping vision, is quite diflferent from the nor-mal: about half of its neurons never recover,and the ability to orient to stimuli across themidline is lost from both eyes (Sherman,1973, 1977).

More selective effects have been ob-tained with selective forms of deprivation. Inthe most extensively studied paradigm, ani-mals have been reared such that their visualexperience is limited to a pattem of lines at aparticular (usually horizontal or vertical)orientation. Initial neurophysiological studiesindicated that visual cortex neurons firedstrongly when the animal saw lines at anglesclose to those of the rearing stimuli (Hirsch &Spinelli, 1970). Later work has qualified thesefindings to some extent (e.g., Gordon, Pres-son, Packwood, & Scheer, 1979; Leventhal &Hirsch, 1975), but the essential details remainintact. As expected, these animals were alsobetter at resolving lines at those same anglesin behavioral tasks (e.g. Blasdel, Mitchell,Muir, &c Pettigrew, 1977; Corrigan & Car-penter, 1979). Similar results have been ob-tained for cortical neurons sensitive to direc-tion of stimulus movement Cynader andChemenko (1976), for example, deprived catsof visual movement perception by rearingthem in a stroboscopic environment Becausethe fiashes of light were very brief, these catssaw the world as a series of "still pictures"rather than one of continuous movement. Inthese animals, cells sensitive to movementwere much less frequently found. Thus cellsin visual cortex were impaired in respondingto specific stimulus characteristics that weremissing from the rearing environment. A be-havioral parallel to this in humans has beensuggested by a persistent reduction in acuity,even while wearing glasses, if astigmatism

went uncorrected in childhood (Mitohell,Freeman, Millodot, & Haegerstrom, 1973).

MorphologyTotal pattem deprivation has pronounced

effects on central visual structures, and partic-ularly upon the visual cortex. Most nerve cellconnections in the visual cortex ocx ur onspines (see Fig. 1). There are fewer of thesespines on dendrites of neurons in visually de-prived animals (Fifkova, 1968, 1970; Rothblat& Schwartz, 1979; Valverde, 1971). This indi-cates that the nerve cells of visually deprivedanimals make fewer interconnections. Whilelater exposure to light can reverse differencesto some extent, at least in dark-reared mice(Valverde, 1971), significant differences per-sist (Ruiz-Marcos & Valverde, 1969). Reduc-tion in the overall amount of dencirite has alsobeen reported for visual cortex neurons fol-lowing dark rearing in some species, againindicating fewer connecdons among neurons(Coleman & Riesen, 1968; Valverde, 1970).Finally, an overall measure of synaptic con-nectivity, the number of synapses per visualcortex nerve cell, was lower in visually de-prived than in normal cats (Cragg, 1975a;Winfield, 1981). A straightforward interpreta-tion is that the complexity of the visual cortex"wiring diagram" is reduced in animals de-prived of visual experience during early post-natal sensitive periods.

While the results will not be detailedhere, differences in the morphology of sub-cortical visual structures (see Fig. 1) have alsobeen reported following visual deprivation(e.g., Fifkova, 1979; for review, see Globus,1975). Overstimulation (constant lifting), aprocedure that eventually damages the rat ret-ina, has been reported to increase spine fre-quency on neurons above that seen with nor-mal diurnal lighting in the lateral genicnilatenucleus (Pamavelas, Globus, & Kaups, 1973)and also in the visual cortex (Pamavelas &Globus, 1976). These findings indicate thatmany brain stnicturos may be affec:ted simul-taneously by experience.

Particularly interesting morphological re-sults have been reported in a selective visualexperience paradigm. Coleman, Flood, White-head, and Emerson (1981) studied the orien-tation of dendrites of visual cortex neurons incats raised witii their visual experience lim-ited to either horizontal or vertical lines, asdescribed above. They found that the outerdendrites were oriented at about 90" fromeach other in the two groups, a result thatcould correspond to tiie visual cortex neuronsselectively modifying their dendrites suchthat they responded to the exposure orien-

542 Cfa£ld DeveU^ment

FIG. 1.—A, A human brain, with much of the right hemisphere removed and many subcorticalstructures omitted to reveal a simplified view of the visual system. Visual information travels from theretina to visual cortex via the lateral geniculate nucleus (LGN). As fibers from (he retina pass back towardthe LGN, some of them cross to the other side, reflecting the general pinciple that a sensory inputoriginating on one side of the body is processed by brain structures in the hemisphere on tihe opposite side.Fibers from each retina which receive light from the right half of the visual field project to visual cortex onthe left hemisphere. Hence, the visual cortex in the left hemisphere "sees" only die right half of the world,through both eyes. Within visual cortex, inputs from each eye are or^nized into adjacent bands called"ocular dcBninance columns." B, A section of visual cortex lowing a neuron, as would be seen through al i ^ t microscope. Visual cortex, which is apiwoximately 2 mm thidc in a 2-year-t^ infent, is actually muchmore densely packed with neurons and Aeir interconnecting fibers than is depicted by this figure. Aneuron in visual cortex might receive, depending on cell type, 10,000-30,000 synaptic inputs to its den-drites, most of which will occur on spines. At (his level of magnification, spines appear as tiny dots alongthe dendrites. C, Detail of a portion of dendrite containing a synapse between an axon terminal (distin-guished by the presence of spheres called vesicles) and a dendritic spine, a small projection bom Aedendrite tunk. For perspective, note thsU: spines are somewhat less than 1/1,000 ofa millimeter wide. Thus,to see a synapse requires the resolving power of an electron microscope.

tation. Tieman and Hirsch (1982) similarlyreported approximately perpendicularly ori-ented visual cortex dendrites in verticaland horizontal stripe reared cats. These stud-ies indicate that the pattem of connectionsamong visual cortex neurons, not merely thenumber of connections, is influenced by vi-sual experience during early development.

Expected ExperienceAn important question is why there are

experience-ejq>ectant or sensitive periods insensory develojmient. On the surfece, it maynot seem to make much evolutionary sense tohave designed an organism that will beforever impaired in its sensory performance ifthe proper sorts ofexperiences do not occur at

Greenough, Black, and Wallace 543

relatively specific developmental time points.The offsetting advantage appears to be thatsensory systems can develop much greaterperfonnance capabilities by taking advantageof experiences that can be expec:ted to beavailable in the environment of all younganimals. Thus many species seem to haveevolved such that the genes need onlyroughly outline the pattem of neural connec-tivity in a sensory system, leaving the morespecific details to be determined through theorganism's interactions with its environment.

The way in which tihis finer tuning ofboth sensory and motor systems is often ac-complished has provided us with some realinsight into the circumstances that may giverise to sensitive-period phenomena. Studiesofa number of developing sensory systems aswell as of peripheral connections in the au-tonomic and skeletal musculature systemshave indicated that synapses are overpro-duced in early development (Boothe,Greenough, Lund, & Wrege, 1979; Brown,Jansen, 6c Van Essen, 1976; Brunjes,Schwark, & Greenough, 1982; Cragg, 1975b;Purves & Lichtman, 1980). Similar findingshave been described in the human visual andfrontal cortex (Huttenlocher, 1979; Hutten-lcwher, de Courten, Garey, & Van Der Loos,1982). As development proceeds, the extrasynapses are lost, such that the final wiringdiagram consists of those synapses that re-main. Two examples serve to illustrate how arefined pattem can emerge from relativelymore chaotic beginnings through selective re-tention of synapses: synapse elimination atthe neummuscular junction and ocular domi-nance column (see Fig. 1 caption) formationin the visual cortex.

Motor neurons in the spinal cord connectwith fibers of skeletal muscle. While a spe-cific spinal location projects to each muscle,the pattem is quite different in the newbomrat from that in the adult. Brown et al. (1976)reported an overlapping pattem in the new-born rat, such that individual motor neuronsconnect to several muscle fibers, and eachmuscle fiber receives connections from sev-eral motor neurons. During the first 2 weeksafter birth, these overlapping multiple con-nections disappear, as all but one of thesynapses on each muscle fiber drop out.Brown et al. (1976) suggest that a selectionprocess cx;curs that involves competition be-tween the various neurons innervating a mus-cle fiber, leaving behind a one-to-one pattem.Precisely what leads to competitive success isnot known, but at least some experimentshave suggested that neuronal activity is a nec-

essary part of the process (Gouze, Lasry, &Changeux, 1983; O'Brien, Ostberg, & Vrbova,1978; Thompson, KufHer, & Jansen, 1979).The important point is that, if the proper con-nections are selectively retained (or if im-proper ones are selectively eliminated), ahighly ordered pattem can emerge from amuch less organized one by the loss of synap-tic connections (Changeux & Danchin, 1977).

The development of ocular dominancecolumns in mammals with binocularly over-lapping visual systems provides an exampleof a similar selection process in the centralnervous system. In species such as cats ormonkeys, closure of one eye during a rela-tively brief postnatal sensitive period causes asevere visual impairment when the eye islater reopened (Wiesel & Hubel, 1963). Theeffect is far more pronoimced and lasting thanthat seen with binocular deprivation (Wiesel& Hubel, 1965). At the neurophysiologicallevel, tiie deprived eye loses most of its abil-ity to control the activity of visual cortexneurons, while the open eye correspondinglygains in control. Thus it appears that the de-prived eye becomes functionally discon-nected from visual cortex neurons. LeVay,Wiesel, and Hubel (1980) have shovra thatthe moncwular deprivation effect involves acompetitive process in which connections ac-tually are lost in the visual cortex. In thebincxiular regions of normal adult monkey vi-sual cortex, inputs from the two eyes termi-nate in alternating bands termed "columns"which are about 400 microns wide. In mon-keys in which one eye has been closed duringdevelopment, the bands are still present, butthose arising from the deprived eye are muchnarrower than normal, and those arising fromthe open eye are correspondingly wider.LeVay et al. (1980), studying the develop-ment of these bands, found that axons fiiomthe two eyes initially have overlapping termi-nal fields (Fig. 2), such that distinct columnsare not present. In normal development, theterminal fields of axons from both eyes gradu-ally and simultaneously regress, such tibat thesharply defined ocular dominance bands ofthe adult emerge. When one eye is deprived,its terminals regress more than normally,whereas those of the open eye retain a largerpart of initial dually innervated territory, thusgenerating the alternating pattem of narrowand wide bands. This work, along with sup-portive evidence (e.g., Guillery, 1972), pointsto the view that a competition process occursin the visual cortex, in which inputs frwm ex-perienced eyes are advantaged. Hypothesesregarding the neural bases of the advantagehave proposed that actively firing synapses

544 Ch&d

Normal Development

Birth Early Postnatal

Monocular Deprivation

Birth Early Postnatal

Adult

Adult

FIG. 2.—Sclwmatic depiction of ocular dominance column envelopment in monkeys reared normallyor monocularly deprived. The left panels represent esut»tantialoveriap of the axonallnanches fitnnthetwo eyes at birtfi. In nonnal development (tc^), die competitive interactions result in equal pruning back ofaxons fixnn each eye in the adult (ri^t panels). After monocular d^xrivf^on, however, axoi^ fitrni &enondeprived eye (solid Unes) rebiin more branches, while the axons fiwn the deprived eye (dashed lines)retain fewer branches (from Greenou^ & Schwark, 19S4; copyright 1984 by Plenum Publishing; reprintedby permission).

are more likely to be preserved, or that syn-chronous firing of the presynaptic terminaland the postsynaptic neuron may stabilize thesynapse (see, e.g. Singer, 1986), a processsimilar to that proposed by Hebb (1949).

These two examples illustrate a majorpoint. In both cases, during a relatively re-stricted period, an expected experience (motoractivity or visual stimulation) participates inthe organization c^ a detailed neur^ ps^^n.The neural manifestation of expectation orsensitivity appears to be t ^ ^ntxluction of anexcess number of synapses, a subset of whichwill be selec:tively preserved by experience-generated neural activity. If the noniuU pat-tem of experience ocKiurs, a normal p a ^ m ofneural organiz^on results. If an abnormalpattem of experience cxxnirs, an abnormalneural organization pattem will occur. We donot, of course, know that similar EHX>cessesunderlie all f^enomena proposed to involvesensitive periods, tmd we shcjl see below thatother &ctors may be involved in the determi-nation of sensitive periods. Nonetheless, itseems clear that the production of moresynapses than can eventually survive, com-bined with an experience-based selectionprocess, is a central aspect of tiie sensitive-period phenomena that have been most ex-tensively studied. Because the deveU^AQgmammal's experience has been predictabletiiroughout the evolutionary history of thespecies, the species has come to count on orexpect its occurrence in die developmentalprocess. We refer to this as experience-expectant information storage.

Schiiz (1978), comparii^ ^tricial (bomunderdeveloped) with precocial species, hassimilarly noted that die overproduction ofsynapses m i ^ t be an indication of readinessfor expected experience. Wiih its eyes openand able to move about, the precocial guineapig's cerebral cortex shows nuuiy more den-dritic spines at birth than that of the newbommouse, which is bom in a relatively altricialstate. However, at the time the mouse's eyesopen, about 2 weeks sSiBx birth, its cortictdneurons have develc^jed a density of spinescomparable to tilrat of the newbom guinea pig.Thus spines matured at the time the animalbecame able to actively explcwe the environ-ment

ContTol of Experience-expectant ProcessesThe character or quality of expected ex-

periences may also phy a rale in (btermioingthe length of time ths^ the devel<q;)ing ner-vous system remains seositive to th^r eSects.For example, since success in com^titionand consequent elimination of alteniAtiveneural pattems is promoted by experience-based neural activity, a rele^ve reduction intiiat activity may proloi^ the competitton pro-cess. Cyn£uier luid Mitchell (1980) found ^ tkittens dark record until 6, 8, en* 10 monthsremained highly sensitive to monocular de-privaticm e£^:ts. Tiiis is in contrast to U^t-reared kittens, in which peak sensitivityto monoctdar de^^vation normally occurswithin die first 2 mcmtiis of life, and nef^lgi-ble eflfects of monocular deprivatlaa are seenin k i^ns reared normally if deprivation be-gins after 3 or 4 months (Hubel & Wiesel,

Greenough, Black, and Wallace 545

1970; Olson & Freeman, 1978). Relativelysmall amounts of nonnal visual experienceappear to set in motion processes that can pro-tect the organism against later deprivation(Mower, Christen, & Caplan, 1983).

The character of experience may not bethe only &ctor regulating the temporal as-pects of sensitive periods. Kasamatsu and Pet-tigrew (1976) initially proposed that thechemical neurotransmitter norepinephrine reg-ulated sensitivity to moncwular deprivation.They found that treatment with 6-hydroxy-dopamine, which reduces brain norepineph-rine, prevented the shift in control of visualcortex neurons from the deprived eye in catsthat were monocularly deprived during thesensitive period. If norepinephrine was re-placed by lcx:al administration into visual cor-tex, however, the ocular dominance shift didoccur in 6-hydroxydopamine-treated cats (Pet-tigrew & Ke^amatsu, 1978). More recent work(Bear & Singer, 1986) has suggested that twoneurotransmitters, norepinephrine and ace-tylcholine, may be involved in regulating de-velopmental sensitivity of the visual cortex.There have also been some reports that dmgsthat interfere with norepinephrine ac^on re-duce or prevent the brain and behavioral ef-fects of environmental complexity diat arediscussed in a later section of this article (Mir-miran & Uylings, 1983; O'Shea, Saari, Pap-pas, Ings, & Stange, 1983; Pearlman, 1983).These results suggest that neurotransmitterssuch as norepinephrine and acetylcholinemay be involved in initiating or maintainingneuronal sensitivity to experience, a role con-sistent wdth the term "neuromodulator," oftenapplied to norepinephrine. Parallel reports ofnoradrenergic regulation of adult memorystorage processes (e.g.. Gold, 1984) suggestthe possibility of a quite general role for nor-epinephrine systems in the governance ofplastic neural prcwesses.

On the "Chalkboard" MetaphorAn important question involves the ex-

tent to which developing sensory systemsmerely follow the pattem imposed upon themby sensory experience, in the manner of a"blank slate," as opposed to selectively utiliz-ing or actively creating information in experi-ence. At the level of the neuron, an equiva-lent question is whether all input promotessimilar stmctural change. It is clear that sen-sory systems have strong predispositions atthe time of birth; for example, the initialstages of the binocular segregation processprecede eye opening in the monkey visualcortex (LeVay et al., 1980), and oriented re-ceptive fields are present to some extent atbirth (Blakemore & Van Sluyters, 1975) and

certain orientations appear to be more predis-posed to arise in the absence of appropriateinput in the cat (Leventhal & Hirsch, 1975).The rudimentary neural organization imposesorder on its input A phenomenon that mayillustrate this is the apparent compensatorychange that has been reported in intact mo-dalities' central representations with damageto or deprivation of other mocialities. For ex-ample, the auditory cortex increases in size invisually deprived or blinded animals (Gyllen-sten, Malmfors, & Nonhn, 1966; Ryugo, Ry-ugo, Globus, & Killackey, 1975). Since audi-tory stimulation is equivalent in deprived andsighted animals, the size increase must de-pend upon some aspect of the increased re-liance upon audition that becomes necessaryin the absence of visual input. That is, thebrain's differential use of the same auciitoryinformation determines the information's ef"-fec:t on brain stmcture. It is but a small exten-sion of this idea to note that individual differ-ences could be preserved even in the face ofidentical environmental experience.

Possible human behavioral reflections ofneural predispositions to select and organizeexperience are also evident. For example, in-fants may have "hard-wired" capacities forcategorical pereeption of phonemes (Eimas,1975) and syntactic structure (Chomsky,1980). The infant's behavioral and affectiveresponses to caretaker speech can make thesocial interaction hi^ily rewarding for bothparticipants, perhaps even encouraging aphonetic adjustment to match the perceptuallimitations of the infant (Femald, 1984). Aninnate predisposition of the infent to smileand make noises, if it exists, could serve theinfant by shaping the caretaker's speech to-ward an optimal form of linguistic input. The-len (1980) has suggested that kicking andother behaviors, while serving as neural foun-dations of mature motor systems, can alsohelp the infant control experience (e.g., as incommunicating distress or pleasure). Fromthis perspective, the infant may often pickand choose from an experiential smorgasbordavailable during development. In fact wesuspect that some types of "expected" experi-ence may rely largely on the infant to producethem.

Early Sensory-System Development:Summary

The primary quality of experience effectsin early sensory-system development that setsthem apart frxim many later developmentalprocesses, as well as from adult leaming andmemory, is the degree to which they are agedepencient and subsequently irreversible. Atthe behavioral level, a relevant human ex-

546 Child Develc^ment

ample may be the loss of perceived phonemicboundaries present in in&nts if the languageto which they are exposed does not utilizethem (Werker & Tees, 1984). At the neurallevel, the irreversibility appears to arise in atleast some cases because a set of synapses hasbecome committed to a particular pE^tem ofoi^anization, while synapses that could havesubserved alternative pattems have been lost.A process seen in tihe brain that may underiiediis is a rapid petJdng of synapse number,followed by the loss of a significant propor-tion of them, as shown in Figure 3. The rateand extent of commitment of synapses may beregulated by both the quality of experienceand intrinsic factors such as broadly act-ing neurcx;hemical systems. In at least somecases, it seems clear that central system or-ganization is not merely "painted" on thebrain by experience, since both die quality ofinformation fmd the way in which it is usedcan aSect the rais of pattem formation as wellas the character of the pattem.

Experience-dependentStorwe in Later Devdkqnnent andA d d d

Many of the effects of experience uponbehavioral development do not appear to ex-hibit the relatively strict age-dependent char-acter associated widi early sensory system de-velopment One reason for this may be that aspecies cannot count on certain important ex-periences to occur at particular points in thelifespan. Another is that much of the informa-tion that an animal or human must acc]uireduring development or adulthood is uniqueto its own particular environment; informa-

High Experience

—~— ExpwisnCBd Z 'Inenparlencefl /

' BhHHiiIng'

- Expectant

^

'Pninlng'

Voung

Relative Age

FIG. 3.—Schematic digram of synapse over-production ("blowning") and deletion ("pruning";Schneider, 1981) during an experience-expectantprcKess (from Black & Greenou^, 1986, Vol. 4, p.28; copyright 1986 by Lawrence Erlbaum As-sociates; reprinted by permission).

tion about the {^ysical characteristics of thesurroundings, the social system and the rolesof specific individuals, and, in hiunans, thedetails of one's langua^(s) and other fonnallyspecified c»}gnitive capacities. It is not cleara priori whe&er the brain mechanisms in-volved in storing these kinds of infimnationare the same as those used for experience-expec^tant prcxesses, alduiug^ evolution tendsto produce new adfy)tations (such as theunique plasticity of the mammaliui brain) bymodifying existing systems, as oppc»eci tocreating entirely new ones. We wifl reviewsome of what is knoviTi about these mwe ma-ture categories of information stcmtge and willthen return to our consideration of neuralmechanisms.

The Envinmmental Complexity PamdigmTile research that has perht^s t au^ t us

die most about mechanisms of cognitive de-velopment in animals tUilizes variations inthe physical and social complexity of ilte rear-ing environment This line of research beganwith Hebb's (1949) rearing of rats as pets inhis home for comparison with laboratory-reared animals, but most researcAiers haveadof^d less life-disrupting labcH tcsry ver-sions of Hebb's home. Most commonly, twoor all of the following three conditions havebeen employed: (1) Environmental complex-ity (EC) animals are housed in grcmps ofabout a dozen in large cages filled witii vari-ous ol^ects with which the animals are free toplay and explore. Often the animals axe givenadditional d^uly e;q>osure to a maze or a toy-filled field. In our work and most others', theplay objects are chan^d and rearrangeddaily. (2) Social cage (SC) animals are housedin pairs or small grou{» in stanciard laboratorycages, without ejects beyond food and waitercontainers. (3) Irtdividual cage (IC) animalsare housed alone in similar or identical labo-ratory cages. The term "enriched corKiition"has been used to describe what we call envi-ronmental comf^xity, but we prefer the latterto emphasize ih&t diese cK>ndition5 representan incomplete attempt to mimic scnne aspectsof the wild envircMiment and should be con-sidered "enriclffid" only in con^»rison to thehumdrum life of the typical laboratory animal.

Behavior.—Since Hebb's (19^) initialdemonstxiMion that home-reared rats weresuperior to Udxniatory-reared rats at leaming aseries of complex msoe pattems, a Icone num-ber of experiments have cxmfirmed diat ratsand mice retted in CCUQE^X environments aregenerally superior on complex, ^petitivetasks. A significant number of experimentshave been directed at particular behavioral

Greenough, Black, and Wallace 547

characteristics that differentiate EC from SCand IC animals, and it seems safe to concludethat no single explanation, such as differentialemotional reac^tivity, better use of extra-mazecues, or differential visual ability, can acx:ountfor the pattem of behavioral differences thathave been reported (Greenough, Madden, &Fleischmann, 1972; Krech, Rosenzweig, &Bennett, 1962; Ravizza & Herschberger,1966; see Greenough, 1976, for review). All ofthese may play a role under certain circum-stances, of course (Brown, 1968; Hymovitch,1952; Myers & Fox, 1963), but the differencesappear to be quite general, extending evento models of Piagetian volume-conservationtasks (Thinus-Blanc, 1981), such that the mostlikely explanation (if not the most satisfying inspecificity) may well be that the groups differin the amount of stored knowledge uponwhich they can draw in novel situations.

It appears that ac tive interaction with theenvironment is necessary for the animal to ex-tract very much appropriate information. Notonly do the EC and SC conditions differ littlewith regard to the average intensity of energyimpinging upon most sensory modalities, butmerely making visual experience of a com-plex environment available to animals other-wise unable to interact with it has little be-havioral effect. Forgays and Forgays (1952),for example, found little benefit to maze per-formance of having been housed in smallcages within the EC environment Similar re-sults have been reported with regard to someof the brain effecrts of EC rearing that are de-scribed below (Ferchmin, Bennett, & Rosen-zweig, 1975).

Morphology.—Following initial reportsthat several regions of the cerebral cortexwere heavier and thicker in EG than in ICrats (Bennett, Diamond, Krech, & Rosen-zweig, 1964) and had larger neuronal cellbodies and more glial (i.e., supportive) cells(Diamond, 1967; Diamond, Rosenzweig,Bennett, Lindner, & Lyon, 1972), detailedstudies began to indicate probable differ-ences in the number of synaptic connections.Differences in the amount of dendrite perneuron, that is, the amount of surfece avail-able for synaptic connecitions, of up to 20%were reported in the upper visual cortex ofrats reared in EC versus IC envirormients&om weaning to late adolescence (Greenough& Volkmar, 1973; Holloway, 1966). Values forSC rats were intermediate, although generallycloser to those of IC rats, in the Greenoughand Volkmar study, and this has tended to bethe case in other experiments in which such agroup has been included. Small differences

in the fi^quency of postsynaptic spines (seeFig. 1) favoring EG rats were also reported(Globus, Rosenzweig, Bennett, & Diamond,1973), suggesting that synapses were notmerely spaced farther apart on the longerdendrites of the EC mts. A direct demonstra-tion that EC rats exceeded IC rats in synapsesper neuron in upper visual cortex by 20%—25% (Tumer & Greenough, 1985) led us foconsider what similar extremes might result ifall neurons in the human brain were equallyplastic. The difference of about 2,000 syn-apses per neuron in the rat would translateinto many trillions of synapses on the 100-200 billion neurons of the human braini

While EC-IC differences (in male rats)are greatest in the occipital, or visual, regionof the cerebral cortex, they ocxnir in otherneocortical regions as well, including thoseassociated with audition and somesthesis andalso regions somewhat functionally compara-ble to the human frontal cortex (Greenough,Volkmar, & Juraska, 1973; Rosenzweig, Ben-nett, & Diamond, 1972; Uylings, Kuypers,Diamond, & Veltman, 1978). Differences in den-dritic field size following similar differentialrearing have also been reported in subcx)rticalregions such as the rat hippoc;ampal formationand monkey and rat cerebellum (Floeter &Greenough, 1979; Juraska, Fitch, Henderson,& Rivers, 1985; Pysh & Weiss, 1979), suggest-ing that this later plasticity is not a phenome-non unique to regions like cerebral cortex thatare most prominent in mammals. A surprisingfinding is that different pattems of EG-IC dif-ferences in visual cortex and hippcxiampusare found in males and females (Juraska,1984; Juraska et al., 1985). Males show greaterdifferences across environmental extremes inthe visual cortex, whereas females showgreater differences in some regions of the hip-pocampus. Althou^ the behavioral signifi-cance of this is still under investigation, itsuggests that very similar experiences mayhave different effects on individually differ-ent brains.

Adult Brain MorphologyUntil relatively recently, it was widely

assumed that, except for certain cases of re-sponse to brain damage, the brain acquired allof the synapses it was going to have duringdevelopment, and that further plastic changewas probably accomplished through modifica-tion of the strengdi of preexisting conneotions. While some morphological and electro-physiological data suggest that changes in thestrength of existing connections may cwcur inresponse to experience manipulations (seeGreenough & Chang, 1985, for review), it has

548 ChiM Devetepment

now becx>me quite clear that new connectionsmay arise as a result of differential housingconditions and other manipulations throu^-out much, if not all, of the life of the rat andprestmiably of other h i ^ e r mammals as well.Bennett et al. (1964) had actually reportedquite early that cortical we i^ t differences in-duced by EC versus IC housing occurred inadult rats, but over a decade passed beforereports appeared that dendritic field size wasaffected by these cx>nditions in both youngaciult (Juraska, Greenough, Elliott, Mack, &Berkowitz, 1980; Uylings, Kuypers, & Velt-man, 1978) and middle-aged (Green, Green-ough, & Schlumpf, 1983) mts. While directmeasurements of synapses per neuron haveyet to be reported in adults under these con-ditions, the correspondence between den-dritic field and synapse-per-neuron measuresin younger animals (Greenough & Volkmar,1973; Juraska, 1^4; Tumer & Greenou^,1985) gives us cx>nsiderable confidence thatthe increase in adult postsynaptic surfece isparalleled by an increase in synapse num-bers. While not al! neuron types affected bypostweaning exposure to diflferential environ-mental complexity may be affected by theseenviroiunents in ^ u l t animals, there is litdequestion at diis point diat the cerebral cortex,and also the cerrfsellar cortex (Greenough,McDonald, Pamisari, & Camel, 1986), retainthe capacity to fonn new synaptic connectionsin response to new experiences.

Effects of Training on Adult BrainMorphology

There has not yet been a specific demon-stration of what might be represented by thechanges in synaptic connections b r o i ^ tabout by differential environmentsd complex-ity, nor are die details of the reU^cmships be-tween brain stmcture and behavioral per-formance very clear. If we follow the ratherhazy terminology of "accumulated knowl-edge" used above, then one might suggestthat these changes have something to do withstoring (anc3/or accessing) that knowledge. Asimple view of nearly a centuiy ago (Ramon yC ^ , 1893; Tanzi, 1893), whic^ has been em-bellished by the mc»re detailed dieorizing ofHebb (1949) and many others, is that mem-ory, in both the very broad and t ^ psycholog-i c^y mcne specific sense, m i ^ t be encodedin the functional p a ^ m of connections be-tween neurons. While demonstrating un-equivcxally the involvement of brain phe-nomena in leaming or memory has been adifficult process for a variety of reasons, it ispossible to perform experiments the out-comes of which would be either compatible

or incompatible with such an interpretation.For example, if the changes in synaptic or-ganization that occur in complex environ-ments are involved in storage of infonn^k>nfrom the experience, then we mig^ be able todetect similar mori^lc^cal changes in ani-mals trained on specific leaming tasks.

Since the experience of training probablyprovides a more limited range of infonnationdian that available in die com^^x environ-ment we m i ^ t expect the mon^ok^ical ef-fects of training to be more limited (andharder to detect). In the first experiment ofthis sort, young adult rats were trained on achanging series of pattems in the Hebb-Williams maze (die maze Hebb used in theinitial test of home-reared rsrts) over a periodof about 25 <kys (Greenoi^, Juraska, & Volk-mar, 1979). In die visual cortex of the trainedmiimals, two types of neurons had more (ten-drite than in nontrained animals, while a thirdtype was un^ected. The unaffected type wasone that had been altered in previous ECstudies. Thus training Ejected a measure re-lated to synaptic connectivity, and die efiectswere more legalized and specific than werethose of the complex environment experi-ence.

In a similfu* experiment, Bennett, ^ Rosen-zweig, Morimrtn, and H^sert (1979) esqiosedweanlii^ rats to a c^ai^png series of m^zes intheir rearing cages for 30 days. The visual cor-tices of these aniinals were heavier dMin thoseof rats kept in IC cages for the same period.Rats hotted with an unchanging simjde nmzepattem were intermedfete between thesegroups, suggesting that die information avail-able in the chaogiog-maze pattems was animportant aspect of dieir results.

A problem in the interpretaticm of theseresults and, in feet, in die interi»?e^on of theenviroi^aental ccHiqpIexity findiE^ as well, isthe possibility that brain efSecte m i ^ t arisefrom stress, sensory stimulation, motor activ-ity, or other nonspecific consequences of thetraining t»^3cedure, radier than from the infor-m^ton acquireci throu#i truning. This prob-lem is, of courw, not trivial. Mid it has beenone of the me^or (}^culties in a long historyof previous experiments designed to eluci-date die molecular biolog^c^ underpinningsof the memory prcxess (see Dunn, 1980;Greenouj^ & Majer, 1972; and Rose, 1981,for perspectives on this work). No s i i ^ ex-periment (and maybe no set <rf ej^Heriments)can rule out all sjtenu^ves, but the involve-ment of genenUly acting fectcffs such as hor-monal or me^iboUc consequences of a train-ing procedure can be examined using a

Greenough, Black, and Wallace 549

within-animal control. One advantage of therat for such work is that the bulk of fibers fromeach eye cross to the opposite side of thebrain, such that the use of a split-brain proce-dure, combined with occlusion of one eye,can restrict visual input from training largelyto one hemisphere. Chang and Greenough(1982) performed such an experiment, againusing the changing maze pattems. A controlgroup indicated that there were no in-terhemispheric differences as a result of in-sertion of the eye cx;cluder (an opaque rat-sized contact lens) for a few hours each day.The group trained with the same eye coveredeach day, in contrast had more apical den-dritic branches on visual cortex neurons inthe hemisphere opposite the trained eye, aresult incompatible with effects of generallyacting hormonal or metabolic effects. Thusthe changes brought about by maze trainingwere specifically a consequence of visual in-put from the training experience.

One further experiment increases our con-fidence in both the generality of the mor-phological effect of training in adult rats andin the unlikelihood that these effects resultfrom general hormonal or metabolic causes(Greenough, Larson, & Withers, 1985). In i trats were trained to reach, bilaterally or uni-laterally, eidier with the forepaw they pre-ferred to use or the nonpreferred forepaw,into a tube for food. A strong preference forreaching with one paw was accomplished byplacing a partition next to the tube that madereaching with the opposite forepaw difficultExtensive training on the nonpreferred pawpermanendy reversed reaching preference, ashad been demonstrated previously (Peterson,1951). It is not clear that something like"handedness" in humans is being reversed inthese rats, as opposed to the animals' merelyusing the paw with which they had devel-oped more skill or even thinking that the con-tingency required them to continue reachingwith the trained paw. We examined theneurons in the forelimb region of the cortexwhose axons project to the spinal region thatgovems reaching. Animals trained with bothpaws had dendrites that were more hi^Iybranched than those of nontrained animals,and hemispheres opposite trained forelimbsin unilaterally trained animals had morebranches dian the other hemisphere. Analysisof the hindlimb region of motor cortex in uni-laterally trained rats indicated no similar pat-tern of assymetry, so the struc^tural changewas specific to both the hemisphere and thecortical area most direcdy involved in thelearned task. We must realize, however, thatthis reaching task involves many other areas

of the brain, as became evident when we ex-amined metabolism of various brain areas inrats performing die task (see Greenough,1984). The complex tasks used in develop-mental psychology research are similarlylikely to involve multiple brain areas, and ex-planations of the role of the brain in suchtasks that focus on a single region (e.g.. Dia-mond, 1985), while interesting, are likely tobe incomplete.

Experience-dependent Information Storage:Possible Mechanisms

Given that complex environment experi-ence and experience in leaming tasks alterthese estimates of synapse number, the pro-cess whereby the new synapses arise is ofsignificant interest. There appear to be twoobvious possibilides: (1) The process of syn-apse overproduction that we described withregard to early sensory-system developmentmight continue. That is, excess synapses, dieexistence of which would be transient unlessthey were confirmed by some aspect of neuralactivity, might be continually produced on anonsystematic basis. Since the nature andtiming of these sorts of experiences could notbe anticipated, synapse formation would haveto occur chronically throughout the brain (orin regions that remain plastic). The effects ofenvironmental complexity or training wouldarise because a proportion of these synapsesbecame permanent as a result of experience-associated neural activity (Changeux & Dan-chin, 1977; Cotman & Nieto-Sampedro, 1984;Greenough, 1978). (2) The production of newsynapses in later development and adulthcK)dmight be dependent upon experience-associ-ated neural activity. That is, synapses wouldbe formed as a result of the activity of neuronsin information-processing anc]/or neuromodu-latory systems. The synapses might be gener-ated nonsystematically at the outset withsome aspect of patterned neuronal activity de-termining the survival of a subset of them(Greenough, 1984). The synapses formed inthis case would be localized to regions in-volved in the information-processing activitythat caused their formation.

The first hypothesis is attrac^tive, giventhe tendency of evolution to conserve mecha-nisms. It also provides a very simple way for aproper set of connections to come to encode amemory. The second hypothesis has its ownattractions, such as the relatively loweramount of metabolic resources required for\oca\y experience-dependent synapse forma-tion and the reduction in potential "noise" inthe nervous system that might be associatedwith chronic generation and degeneration of

550 Child Development

synapses. Most of the same genes wouldprobably be involved in the construction orstabilization of synapses, regardless of the ini-tiating event. Moreover, the initiating eventfor intrinsic and extrinsic tri^ering of syn-apse formation could involve a final ccmimonpathway or <K)mmon mechanism, suc^ as theactivation of neuromodulatory systems. Fi-nally, die second hypothesis has been madefar more attractive by the recent appearanceof data that are more consonant with it thanwith the first

Bapid, Active Synapse Forrruition in theAdult Brain

Two lines of evidence have emerged thatcan be interpreted as suggesting a dynamicsynapse-formation prcKess in response to ex-perience-associated neural activity in theadult brain. TTie first arises from a phenome-non induced by elec^trical stimulation ofneurons that has been proposed as a modelfor adult Icmg-term memory, long-term poten-tiation (LTP). In the hippcKamxms xnd a num-ber of other brain regions, stimulation of ax-ons at high frequencies can give rise to anincreased postsynaptic response to test stim-uli (Bliss & L0mo, 1973; see Teyler & Foun-tain, 1987, in diis issue). With proper stimulussequences, this elevated responsiveness canpersist for up to several weeks. There are sev-eral hypodieses as to its neural basis. One,that additional synapses are fonned, is basedon the work of Lee, Schotder, Oliver, andLynch (1980) and Lee, Oliver, Schotder, andLynch (1^1), who reported that synapsesform in the hippoc^unpus in vivo £uid in an invitro tissue slice preparation following LTP-inducing stimulation. The synapses form sur-prisingly rapidly. Chang and Greenough(1984) noted that synapses formed within 10-15 min in vitro. This rate of formation is sim-ply too rapid to arise from the chronic synapseturnover proposed in the first hypothesis. Re-gardless of whether LTP is related to mem-ory, or synapse formation to LTP, the hct re-mains that the adult brain, or at least thehippocampus, is capable of generating newsynapses rapidly in response to neural activ-ity.

The second finciing involves what we be-lieve to be a marker of newly fonningsynapses, polyribosomal aggregates (PRA),the protein-synthesizing "fectories" of cells.Steward (1983) reported that PRA were foundfrequendy within postsynaptic spines (odier-wise rare) during the process of re-formationof synapses thf occurs following damage to apart of the hippcx^ampus. Hwang and Green-ough (1984) similarly found, in a develop-

mental study, a large increase in the numberof PRA in spines in rat visual certex duringperiods c^ peak s>i:iapse formation, comparedto adult values, llius, in both sitoati(ms, PHAin spines appear to indicate die formati(Hi ofnew synapses. We do not know, of course,that synapse fcnma^on in late develojwnent oraduHhcKx] resembles early development orthe response to damage. However, if it does, arecent finding su^ests tluit behavioral expe-rience can promote syn^rae formatii^i, as thesecond hypothesis above suggests. If animalsin environments of diflferent complexityformed equivalent number of synapses, butmore synapses were ccmfinmed or stabilizedin EGs, we m i ^ t expec: die frecpiency ofPRA in spmes to be equivalent across thegroups. GreeiK>u|^, Hwang, and German(19^) studied sym^es in upper visual cortsxof rats reared for 30 ciays after weaniog in EC,SC, or IC environments. PRA were consider-ably more fi^quent in spines in the EC ani-mals, suj^esting that more new synapseswere forming.

Given our knowledge that there we moresynapses per nexuun in EC mts, and otherdata indicatlRg that PRA in s|Hnes marksnewly formed synapses, this residt suggeststhat experience-^pendent syni^jse fonns^ionoccurs in die develc^meD^ environmentalcom^Jexity parad^tn. Of cK>urse we mustkeep in mind that PRA may a&gregi&te inS{nnes to perfonn functfons ass<x:iated withincreased artivity of syru^ses or iiH)difi<^onof dieir streng^. We now need to find otherways to identify newly fimning syna^es andmust determiiie whether similar increases inspine-located PRA ocxiur in adult animalsduring leaming. The ciata to diis point how-ever, su^pst th^ synapses form in responseto experierwe from, wi^h inf&rmation is to bestored in the postweaning environmentalcomplexity paradigm.

Sumnuiry of Later Development arui AdultLeaming

The daA& reviewed here suggest thatdiere is a fundamental difiSwence betweenthe processes governing the formation ofsyn£^)ses in early, age-loc3ced sensory systemdevelc^ment mid diose governing synapsefomaatkm during l^er cievelopment andaduldKX>d. Experience-expectant {Mroeessesfound in eju-Iy devek>|Hnent f^^^ear to pro-duce a sm^us of synopses, which are dienpmned back by ei^rience to a functionalsubset. In later develcq)ment and adulthood,synapses appear to be ^nerated in responseto events that provide inftmnation to be en-coded in the nervous system. This later expe-

Greenough, Black, and Wallace 551

rience-dependent synapse formation may dif-fer from that of early development in that it islocalized to regions involved in processing in-formation arising from the event, but may besimilar in that synapses are initially formed ona relatively unpattemed basis, with aspects ofneural activity resulting from the event deter-mining the selec^dve preservation of a subsetof diem. The cnimulative effect of many suchindividual experiences may appear to be asmoothly increasing supply of synapses, asshown in Figure 4.

Some Cautionary NotesPresumably we need not point out to

most readers that neuroscience involvessignificant amounts of disagreement and con-troversy, as do other disciplines, and some ofwhat is said here would be considered contro-versial by certain of our colleagues. Forsimplicity, we have painted a much morestraightforward picture here than probably ex-ists. For example, there is significant evi-dence for an active synapse-formation compo-nent in early sensory development. Winfield(1981), for example, noted that the peak num-ber of synapses per neuron was lower in visu-ally deprived than in nonnal kittens, suggest-ing that visual stimulation promotes extrasynapse formation (although it remains possi-ble that this reflects reduced preservation ofsynapses in a population diat is intrinsicallygenerated over time). There is also evidence

Experience - Dependent

Young

Relative Age

FIG. 4.—Schematic diagram of synapse forma-tion and selective retention during an experience-dependent process. The arrowheads mark salientexperiences that generate local synaptic over-production and deletion (small curves). The cumu-lative effect of such synaptic blooms and prunes is asmoodi increase in synapses per neuron, which isgreater for the animals with more experience (fromBlack & Greenough, 1986, Vol. 4, p. 38; copyright1986 by Lawrence Erlbaum Associates; reprintedby permission).

for a burst of synapse formation and axonaland/or dendritic growth at eye opening or firstexposure to l i ^ t in rodents. Several studieshave indicated a burst of synapse formation atabout the time of eye opening (Blue & Par-navelas, 1983; Hwang & Greenou^, 1984;Miller, 1981; Miller & Peters, 1981), aldioughthere is some evidence that the burst maybegin prior to eye opening (e.g., Valverde,1971), leaving open the possibility of an in-trinsic trigger. Exposure of rats to light for thefirst time at later than the nonnal age of eyeopening may also trigger some synapse forma-tion (Cragg, 1967), as well as the synthesis ofprotein (Hose, 1967), including tubulin, a ma-jor molecular component of axons and den-drites (Cronly-Dillon & Perry, 1979). In anartificial imprinting situation, in which chickswere exposed to light for the first time in theform of a flashing amber stimulus, RNA andprotein synthesis in the forebrain increaseddramatically (Bateson, Rose, & Horn, 1973;Horn, Rose, & Bateson, 1973). And, duringthe recovery that can be made to occur inmonocularly deprived monkeys by reversingwhich eye is sutured shut, there is evidencefor active extension of the axons associatedwith the previously deprived eye (LeVay etal., 1980). Thus, while synapse overproduc-tion appears to be a dominant aspect of theearly organization of the visual system, it islikely to be accompanied by some experi-ence-dependent growth. Nonetheless, on thebasis of the evidence to date, the relative em-phasis on intrinsic generation and experien-tial selection on a sensory system-wide basisseems quite clear in early development anddie generation of synapses in later develop-ment and adulthood appears to be much moredependent upon extrinsically originatingevents. It thus seems reasonable to view sen-sitive period versus continuing developmen-tal information-storage phenomena from thisperspective.

Finally, our dichotomy of information-storage mechanisms is based upon studies ofa limited number of brain regions. Althoughmany developing systems within the brainother than the visual system go throughphases of synapse overproduction, and expe-rience effects on various aspecrts of the devel-opment of these systems have been reported,it remains quite possible that other systemsmay operate in difFerent ways. Similarly, ex-perience-dependent synapse formation isquite probably not characteristic of all regionsof the later-developing and adult nervous sys-tem, and there may be other mechanismswith quite different properties whereby ner-vous systems store information. Recendy, for

552 Develoimient

example, we found that an electrophysiolog-ically detectable phenomenon in the hip-pcxampal dentate gyms (p^haps similar toLTP), wiiich was apparent immediately afterpostweaning rearing in a complex environ-ment had entirely diss^peaxed within 30days (Green & Greenough, 1986). In contrast,denciridc branching di£ferences induced invisual cortex in diis paraciigm are rela^velystable for at least that long (Camel, Withers, &Greenough, 1986).

Thus, while the separation of experienceeffects upon brain development into catego-ries based upon the existence of neural antici-pation of the experience is comp^ble withcurrent data, these categories may well not becomprehensive. Nonedbeless, recognition (1)that a cemmon aspect of early development ofsensory systems may be overproduction ofsynapses in expectation of experiences diatwill determine dieir selec^ve survival, and(2) that later developmental and adult infor-mation storage may involve synapse forma-tion triggered by experience, may offer a newlevel of understanciing of phenomena previ-ously described as merely relsUed or unre-lated to sensitive periods in development.

Some Guidelines for Studying Effects ofExperience on Development

Monolidiic approaches, in which the de-velopment of the brain (or the organism) istreated as a unitary phenomenon, are unlikelyto be very useful and, in fecrt, may be mislead-ing. For example, Epstein (1974a, 1974b) hasproposed that "phrenoblysis," or spurts ofgrowth of the whole brain during selec^d pe-riods of development (purportedly corre-sponding to stages of co^itive develofHnent),characterizes species as diverse as hunumsand mice. While findings of odiers have foiledto replicate Epstein's observations in eidierspecies (e.g., Hahn, Waiters, Lavooy, & De-Luca, 1983j McCall, Meyers, Harbnan, &Roche, 1983) and Epstein's analytical proce-dures have been discredited (Marsh, 1985),the general concept, that die brain as a wholedevelops in bursts or stages, continues to at-tract attention to ^enomena that probablydo not exist (e.g., Spreen, Tupper, Risser,TuoWco, & Edgell, 1984). Certainly any rec-ommendations that educational practices bemodified to accommodate such bursts (e.g.,Epstein & Toepfer, 1978) are not appropriateat this stage. Several lines of evidence indi-cate that while discrete brain regpionsdefinitely progress throu^ somediing like"spurts," in terms of such processes as thegeneration of nerve cells and of connectionsbetween them, different brain regions do so

out of synchrony and in a reliable develop-mental sequence. First some older but gener-ally ignored da.ta. on human cerebral cortexdevel<^nient (ConeJ, 1^9-1967), w^ich wehave plotted in Figure 5, show t&AieT strikingciifferences in the pfUtem of growdi acrossbrain regions. While many regions of die cor-tex show some synchrony in the pattem ofthickness fluctuations w^ a^, odber regumsare not in synchrony with them. Radier dianshowing clear peaks, for example, the prefron-tal cortex appears to cx>ndnue to grow thickerthroughout the first 6 years of life. A similarrelative delay in the deveiopmeat of frontalbrain regions is evident in the prcrtracted (10-14 years) prcxess of achieving stE^e synapticdensity values in hunstn fr<mtid cortex (Hut-tealocj^r, 1979), compared with the n^idst&hilizai^a (1~2 years) seen in human visualcortex (Huttenlodier et al., 1^^). A meta-bolic {Mirallel, perhaps, to tiwse rept»is is dieChugani and Kielps (1^6) report diat glu-cose utilization in humm^ in&nts was init^lyhi^es t in sensorimotor cortex and only laterrose in the frontal cortex.

In the lis^t of diese findii:^, die reportby Rakic, Bourgeoui, Ec4cenhc^ Z^ecevic, andGoldman-i^kic ( 1 ^ ; see alJso G<^c)nian-RfUdc, 1^7, in this issue) diat there is a strik-ing temporal synchrony ac ross cxnUcal areasin developments^ chfuiges in density ofsynapses is rather stuinising.synaptic density measures can besince diey do not clearly reflect either dienumber of synapses within a functioned areaor die number of synapses per nerve cell.Tumer and Greenough (1985) found thatwhile the number of synapses per neuron wasabout 20% h i ^ e r in rats reared in ccnnplexenvironments, the density of synapses (inneuropil, as in Rakic etal., 1986) did not differin these groups, ap|xu«ndy because dte tissuevolume of die dendrites, axons, glial cells,blood vessels, etc. necessary for additionalsynapses pushed the new synapses as &as^axt as they were in IC rats. As Bermett et al.(1964) had shown years earUer, the vcdume ofthe cortex as a whole simply increases to ac-commodate these needs.

Thus, while counterexEunpfes exist, itseems clew that f^nc^rony in brain develop-ment meiite thecsetk^ attention. Theoristshave a r^ed th^ by st t^^risg diemental schedule for mt^unition ofbr^n regions, die humtm species (and o&ermamrmUs, for which such pattems are also ev-ident) may have gained substantial advan-tages, most importandy by allowing one de-velopmental system to provide a suitable

Greenough, Black, and Wallace 553

Visual Cortex

Agihr

Parietal Cortex

A9I [rmntM)

Temporal Cortex

A91(monUnJ

Motor Cortex

Agi (month!)

Prefrontal Cortex

framework for a subsequent experience-sen-sitive system (Black & Greenough, 1986;Turkewitz & Kenny, 1982). This "stage set-ting" possibility is most interesting for humandevelopment, for example, where early socialand communicative skills can establish thefoundations for adult language, and whereearly visual and motor skills can help the in-fant master spatial and causal relations. Theactive participation of the infant in acquir-ing and organizing experience becomesparamount if one prcwess is setting the stagefor a subsequent experience-dependent pro-cess. In summary, sensitive periods must becharacterized in terms of their time course,the brain regions and mechanisms employed,and the organism's involvement in shapingexperience.

This perspective may be helpful to bothdevelopmental psychologists and neuroscien-tists in explaining the meaning of infancy. Forexample, a conjecture that a particular devel-opmental process has a sensitive pericKi(s)(e.g., language acquisition) can now generatetestable hypotheses about neural changes thatmust accompany it. For example, a fixed timecourse for language acquisition would suggesta peak in cortical thickness or synaptic num-bers shortly before the start of a hypotheticalexperience-expectant period. Such predic-tions could be quite specific about what brainregions arc involved and when the changesoccur. After examination of appropriate braintissue, findings of different time courses orthe involvement of other brain regions canrefiect back on the original theory, suggestingdifferent influences and constraints. Giventhe complex and long period of language ac-quisition, a theory invoking a single, pro-tracted "sensitive period" may eventually beexpanded to reflect the multiple involvementof many brain regions, each with its own timecourse and experiential sensitivities, as has

FIG. 5.—Cortical thickness in humans isplotted as a function of age and region of die cere-bral cortex. Symbols widiin regions identify partic-ular sites that were measured (data frotm Conel,1939-1967). Postnatal changes in cortical thicknessindirectly reflect the addition or deletion of braincomponents, for example, synapses, neurons andsupporting cells, blood vessels. A tendency for apeak in cortical thickness between 10 and 20months of age is evident at many sites in visual,parietal, temporal, and motor cortex, and a secondpeak may also cxxiur near 50 months of age at somesites. A clear pattem of peaks and troughs is muchless evident in prefrontal cortex, which seems toincrease gradually in thickness over die first 4 yearsof life.

S54 Development

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