Preservation of accurate spatial memory in aged rats

Neurobtologx of Aging, Vol 6, pp 219-225, 1985 ©Ankho International lnc Pnnted m the U S A

0197-4580/85 $3 130 + 00

Preservation of Accurate Spatial Memory in Aged Rats WILLIAM

W

BEATTY, REX A

BIERLEY

AND JEAN G

BOYD

D e p a r t m e n t o f Psychology, North Dakota State Untverstty, Fargo, N D 58105 R e c e i v e d 18 S e p t e m b e r 1984 BEATTY, W W , R A BIERLEY AND J G BOYD Preservanon of a~turate spat:al memory In aged rats NEUROBIOL AGING 6(3) 219--225, 1985 -Male rats were tested in an 8 arm radial maze from 6--26 months of age with 5 hr delay tmposed between chotces 4 and 5 At 26 months thetr spatted memory was more accurate than when they were first tested at 6 months and also more accurate than that exhtbtted by another 5 month old group tested concurrently However, these old rats acquired a noved spatted habtt more slowly than the younger ammeds In a subsequent study, we compared the acqmsttton of accurate spatted memory by rats that were 3 or 21 5 months old at the start of training Older rats adapted to the maze more slowly and reqmred more sesstons to achieve criterion wzth no delay tmposed dunng the test There was no rehable dLfference m acqmsltton when a 1 hr delay was tmposed between choices 4 and 5, but the old rats learned more slowly wtth a 5 hr delay On memory tests after criterion performance had been achteved, the older rats performed as well as the younger animals at all delay mtervals Aged rats are defioent m acqumng the skdls reqmred for accurate spatted memory, but once acqmred these skills do not deteriorate The poss~bdtty that other "'memory" deficits assoctated wtth agmg mtght be edlevtated by overtralmng is discussed Agmg

Spatial memory

Radtedmaze

Rats

D E F I C I T S m learning complex mazes and other spatial tasks are well estabhshed correlates of advancing age m several species [4, 6, 9, 19, 21, 22, 28, 39, 41] In recent years the radial maze has become a popular task for studying spatml memory in rats When tested m th~s apparatus rats display remarkably accurate memory for spatial locations which Is unusually long hved F o r example, ff a delay is imposed between the 4th and 5th choices m an 8-arm maze, young rats maintain accuracies of 85% or better on choices 5-8 for delays of up to 6 hr [17,35] Developmental studies using cross secUonal designs indicate that spatml memory m the radml maze is less accurate m old rats than m younger ammals [6, 27, 39] Dunng a series o f psychopharmacologlcal studies [13, 15, 16, 21] tamed at dlscovenng the neurotransm~tter systems responsible for maintaining accurate spatial memory at long retention intervals we observed that performance on control sessions remained highly accurate desplte the fact that rats were more than 20 months old Thus ~t appeared that spatml memory m~ght not mewtably deteriorate w~th age To test th~s we retested the rats at 26 months after 3 months without training

nal 16 rats m these drug studies, 5 &ed between 21-25 months of age A comparison group (N=21 males) was obtinned from Holtzman at 2 months of age, pretramed and tested at the same time as the old animals received their last radial maze tests at 26 months of age At this Ume the young rats were 5 months old and mvolved in an experiment assessmg the effects of naltrexone on spatial memory [13] Throughout the expenmentaUon the rats were caged singly with free access to water m an air-cond~t~oned ammai room (22-+3° C) that was illuminated from 0700-2100 by overhead fluorescent hghts The were maintained on a restricted feed° mg schedule designed to mamtam body weight at 85% of the free-feeding level adjusted for growth All behavioral tests occurred dunng the dayhght port~on of the L D cycle

Apparatus-Radtal Maze The elevated 8 arm maze was made of wood pmnted whtte and was shaped hke a rimless wagon wheel Each arm (74x9 cm) extended from an octagonally shaped central hub (36 cm across) Black plasuc sidewalls (3 5 cm high) extended the length of each arm Small metal cups, mounted at the end of each arm, served as receptacles for reinforcers Gmllotme doors surrounded the maze and controlled access to the arms The room housing the maze (3 m 2) was cluttered with runmng wheels, a steam hne w~th valves and hoses and other surplus eqmpment which provided a rich variety of extramaze cues A 40 W incandescent bulb mounted 150 cm above the center of the maze prowded tllummatlon

EXPERIMENT 1

Ammals The rats m the longitudinal phase of the study, the " o l d " rats ( N = I 1), were males of a Sprague-Dawley strata originally obtmned from the Holtzman C o , Madison, WI, at 3 months of age After prehmmary trmnmg they were tested m a series of psychopharmacologtcal studies from 6-22 months of age Their past drug history Is summarized m Table 1 and described more fully elsewhere [13, 15, 16, 21] O f the ongl-

Cross Maze The cross maze was constructed o f clear plasttc w~th a

219

220 grid floor made of bronze welding rod Start boxes measured 4 9 x l l x 1 4 cm, goal arms measured 61×11x14 cm A large relay rack was located near the end of the West goal and the door to the room was near the end of the East goal A large poster marked the North start box, the experimenter sat next to the South start box Metal cups mounted on the end walls of each goal served as receptacles for reinforcers Gudiotme doors at the end of the start arms controlled access to the maze A 40 W incandescent bulb mounted 150 cm above the center of the maze provided tllummatlon

Procedure The pretrammg procedure is described m detail elsewhere [21] In brief, the rats were adapted to the maze by allowing them to explore and eat from the food cups at the end of the maze When they ate from all 8 arms m 10 mm, formal pretralmng began WRh all arms boated with a single 190 mg Noyes pellet, the rat was placed into the central hub and all 8 gudlotme doors were roased The session continued until the rat ws~ted all 8 arms and food was never replenished during the session Hence, the rats were required to learn a winshift strategy and reentries into arms prewously wsRed during the session were considered errors Trmmng continued at the rate of I sessmn per day until the rat achieved 5 crltenal sesmons m a row A c n t e n a l session occurred when the rat entered 7 dLfferent arms in the first 8 chomes and all 8 arms m the first 10 choices Next a l hr delay was imposed between the 4th and 5th choices As performance stabilized the delay was extended to 5 hr By the end of pretroanmg which required about 70 days for both groups all rats were malntammg performance of at least 80% correct on choices 5-8 at the 5 hr delay Next the rats participated m eRher a series of pharmacological studms (the " o l d " rats) or a single experiment concerned w~th the effect of naltrexone on spatml memory (the young rats) The specific drug treatments are described elsewhere m detail [13, 14, 16, 21] but the general design of all studies was similar The rats received a particular dose of the actwe agent being tested every third day and a control treatment (no mject~on or a saline mject~on) on the other 2 days With the exception of amphetarmne, none of the drugs affected spatial memory consistently Amphetamine d~srupted retention accuracy, but only if g~ven just before testlng [ 16] Performance recovered by the following day with all drugs tested From 22-25 5 months of age the old rats were moantalned with free access to food and were not tested At 25 5 months of age they were again reduced to 85% of free feeding body weight and readapted to the maze for 6 days Next they received 5 tests w~th no delay between choices 4 and 5 Then memory was studmd with delays of 45 mm (2 tests), 90 mm (2 tests), 3 hr (2 tests) and 5 hr (5 tests) interpolated between the 4th and 5th choices By this last series of tests 2 of the old rats had broken their upper incisors and could no longer eat solid food They were moantoaned on a commercial hqmd dmt (Chocolate Sport Shake, MldAmerlca Farms, Spnngfield, MO) and received 0 25 cc of the dmt for correct choices Except for these latter tests, d u n n g which the old rats received no drugs, other radml maze data reported are the average performance for no treatment tests days d u n n g the various pharmacological studies [13, 14, 16, 21] Data for the young comparison group are the average of their no treatment sesmons On the day after completion of the radml maze tests the rats were adapted to the cross maze which was housed m

BEATTY. BIERLEY AND BOYD TABLE 1 MEAN PERCENT CORRECT ON CHOICES5-8 IN THE RADIALMAZE

WITH A 5 HR DELAY BETWEENCHOICES4 AND 5 Age (months) 6

85 13 5 15 16 17 5 18 19 20 21 5 26 5t

Percent Correct* 88 2 _+ 9 9O 4_+ 2 91 9_+ 5 94 4 -+ 2 92 3-+ 3 91 2-+ 9 91 8-+ 6 92 5-+ 6 92 0 - + 2 0 93 9_+21 95 9_+15 9O 7 - + 1 2

Concurrent Drug Treatment and Dose (mg/kg) Scopolamme Scopolamine Propranolol Phentolamme Halopendol Methyserglde Halopendoi Naloxone Amphetamine Morphine None Naltrexone

(1-2) (I-5) (10-20) (5-20) (0 5-1 0) (5-15) (0 25-0 5) (1-10) (1-2) ( 1-15) (0 1-10)

*Performance on untreated control tests Each point is the mean of 6-16 tests per rat at each age (+SEM) ?Performance by the young group trained at the same t~me as the 26 month tests

another room Dunng the 3 adaptation sessions the rats explored the maze and ate 20-25 45 mg Noyes pellets from each of the cups in the goal arms On the next day each rat received 10 test trials to determine its goal preference On this day all choices were rewarded with 2 pellets On the followmg day the rats were trained on a win-stay spatial habit The correct goal (East or West) was the one less often entered d u n n g test trials (or determined by chance if the rat showed no preference) Correct choices were rewarded with 2 pellets The two old rats that could not eat solid food received 0 10 cc of the liquid diet for correct choices Trials were massed with a 10-15 sec ITI and the start box (North or South) vaned randomly from trial to trial Training continued using a non-correction procedure until the rat met a criterion of 10 consecutive correct choices or 50 trials occurred If the rat made a correct choice on trial 50 but had not met criterion testing continued untd it met criterion or made an error In the latter case, training resumed the following day The young and old groups differed m the amount of prior radml maze training they had (100 vs 450 sessions) as well as in age Smce the win-stay habit required m the cross maze requires exactly the opposRe strategy from the win-shift habit that Is essentmi for successful performance m the radml maze, this Is a potentially serious confound In an attempt to evaluate the influence of amount of prior radml maze trmnmg we stud~ed two addmonal compartson groups of the same sex and strain One group (N = 19) was 12 months old at the Ome of cross maze testing and had received 225 radial maze tests (see [25] for a more complete description of their past testing history) The other group (N=66) ranged in age from 3-12 months and had no p n o r testing m the radial maze These rats were the sham-operated and unoperated controls from a study companng the behavioral effects of long term alcohol exposure and various forebrmn lesions that is reported elsewhere [12] At the conclusion of testing the old rats were sacrificed under deep Chloropent anesthesia and perfused mtracardmlly with sahne and formahn Their brains were

A G I N G AND SPATIAL MEMORY examined for signs of gross pathology, but no such signs were observed RESULTS

Radial Maze Table l summarizes performance on the radial maze in terms of percent correct on choices 5-8 Here it can be seen that throughout the extensive series of drug tests from 6-22 months of age performance remained highly accurate d u n n g control sessions When the old rats were returned to the radial maze at 25 5 months of age after 3 months without training, they rapidly regained accurate performance D u n n g tests at 0, 45 min, 90 mln and 3 hr delays they averaged 99, 96, 99 and 98 percent correct respectively As seen in Table l these old rats achieved their highest performance at the 5 hr delay on the tests at 26 months of age A repeated measures analysis of variance disclosed a reliable main effect of age, F(10,100)=3 I l, p < 0 002, and subsequent analyses showed that performance was more accurate at 15, 21 5 and 26 months of age than when the rats were first tested at 6 months of age, Fs(l,10)>7 20, ps
221 averaged 4 9% on this index By comparison, the young control group visited the same 4 arms on 4 I% of successive tests In an 8 arm maze there are 70 different combinations of 4 arms so chance reentry into the same 4 arms on consecutive days would occur on l 4% of the trials Both young and old rats were more likely to select the same 4 arms on successive days than would be expected by chance (p<0 05), but m absolute terms this behavioral pattern occurred infrequently Therefore, it seems unhkely that either group converted the working memory problem into a reference memory task Another way the rat might simplify the working memory task is to enter the same arm on its first choice day after day To determine whether or not the old rats learned to do this we computed the percentage of times each rat entered its most frequently visited first arm on the first choice of the session at different stages of the experiment On this measure performance consistently changed from an average of 20 3% to 30 1% from 6 to 26 months of age, F ( l l , l l 0 ) = 3 92, 0 < 0 001 At 26 months the old rats displayed a stronger first arm perference than animals in the young comparison group (Mean=20 9%, t(30)=4 09, p < 0 001) Although the increase m first arm preference with age was statistically reliable, it should be noted that the strength of the preference was not great in absolute terms It is not at all clear that this modest age-related change can account for the striking preservation of accurate spatial memory displayed by these aged rats There are, of course, countless other ways m which the sequence of choices rats make In the radial maze can and do deviate from strictly random sequences, but is not obvious how most of these departures from truly random choice patterns could aid the animal in remembenng the arms visited 5 hr earlier And while Markowska, Buresova and Bures [30] have suggested that highly trained rats might be able to achieve accurate performance at long days by learning to utilize subtle intramaze cues or by employing errorcorrecting strategies, we have shown that these possibilities are most unlikely [29] Using a maze rotation technique that pitted extramaze cues against Intramaze stimuli on a probe test, we showed that highly trained animals consistently made their choices on the retention test on the basis of the extramaze cues even when reinforcement was delivered for choosing on the basis of intramaze cues but not for choosing on the basis of extramaze cues While it is possible that the rats used some umdentlfied nonspaaal strategy as a mnemomc aid to simplify the problem, this seems unlikely Instead, it seems probable that both young and old rats utilized the rich array of extramaze cues to solve the task In a spatial fashion By virtue of their more extensive experience on this radial maze the older rats were more proficient Until it is rigorously shown that accurate spatial memory in aged rats IS unaffected by procedures that preclude response patternlng, this conclusion must remain tentative

Cross Maze As seen In Table 2 pnor training in the radial maze did lead to slower learning in the cross maze Reliable overall differences were observed on both trials and errors to criterion, Fs(3,101)>8,69, p s < 0 0 0 1 and subsequent t-tests showed that all groups with radial maze experience learned more slowly than the naive controls (IS>3 43, p s < 0 001) Of greater Importance was the finding that the 26 month old rats required more sessions and made more errors in meeting criterion than either of the two groups w~th prior radial maze

222

BEATTY, BIERLEY AND BOYD TABLE 2 CROSS MAZE PERFORMANCE

Age (months)

N

No Prior Radml Maze Tests

26 12 6 3-12

I0" 1St 20* 60*

450 225 I00 0

Mean Performance to Criterion (-+SEM) Tnals

Errors

503±56 360~20 370±26 257--_10

140-+17 93-+07 93-+08 66-+04

* I rat could not be adapted to the maze t4 rats could not be adapted to the maze *6 rats could not be adapted to the maze

experaence (ts>2 41, p s < 0 05) Since the latter two groups did not dtffer on either measure of learning the cross maze despite large differences m the number of prior radial maze tests they had experienced, it seems hkely that the deficit in learning this novel spatml task displayed by the old rats is pnncipally related to their age Obviously this conclusion cannont be drawn with certatnty EXPERIMENT 2 Although deficits m spatial memory have been reported in aged rats of the Long-Evans, W~star and Fischer 344 strains [6, 27, 39] we know of no data on age differences in this task for animals of the Sprague-Dawley strain To address this issue we studied acqmmtlon of radial maze behavior in male Sprague-Dawley rats using a cross sectional design METHOD

Ammals Both groups were male Sprague-Dawley rats purchased from Holtzman The rats m the young group (N=14) were acqmred at 2 5 months of age and began trmnmg at 3 months of age Rats in the old group ( N = l l ) were shipped to the laboratory at 7 months of age Housing and general maintenance procedures were the same as in Experiment 1

Procedure The old rats were fed ad hb and left undxsturbed untd they were 18 months old From 18--21 months of age they were weighed and handled twice weekly, by the end of this period they could be handled easily At this point all rats were reduced to 85% of their free feeding body weight and matntatned at tMs level throughout the experiment Prior to depnvaUon the old rats ranged m weight from 587 to 993 g; free feeding weights for the young rats ranged from 364 to 449 g For the young rats body weight levels were adjusted for growth For some of the old rats ~t was necessary to reduce body weights to matntatn adequate motivation 3 were depnved to 75% and 4 to 70%, respecUvely, free feeding levels The same radial maze used in E x p e n m e n t 1 was employed m the present study The animals were adapted to the apparatus by placmg them into the maze for 10 mm with all arms batted It qmckly became clear that the old rats adapted to the maze more slowly than the young animals In 4 cases ~t was necessary to leave the old ammals on the maze for 30-60

mln When the rats entered and ate the food from 6 of the $ arms we considered that they had met the adaptation criterion, at this point we began trmnmg at 0 delay As m Experiment 1 the rats were tested untd they met the criterion o f e n t e n n g 7 different arms d u n n g the first 8 choices and all g arms m the first 10 choices for 5 consecutive days Sessions concluded when the rat found all 8 pellets or 10 mln elapsed. After they met this criterion the rats were given 5 addmonal sessions at 0 delay to assess the stabdRy of performance. Then a delay of 1 hr was imposed between choices 4 and 5. Training continued until the same criterion described above was met After 5 post c n t e n a l sessions at the 1 hr delay the retention interval was increased to 5 hr When criterion was met at this delay, the rats received 5 additional sesmons to evaluate the stability of their performance Testing at the 5 hr delay was terminated after 50 sessions If the rat had not met criterion unless the 50th session was a c n t e n a l session If it was, testing continued until the rat met criterion or had a n o n c n t e n a l session D u n n g testing at 1 hr delay 3 of the old rats died, their data from 0 delay are not mchided These animals required 22, 25 and 54 sessions to meet criterion and committed 14, 18 and 108 errors m achieving criterion Exclusion of their data in no way alters the conclusions At the conclusion of testing the other 8 rats were sacrtficed under deep Chloropent anesthesia and perfused mtracardially with saline and formahn Subsequently the brains were sectioned on a Cryostat at 40 #. One rat was found to have a large pltmtary adenoma which compressed the postenor hypothalamus, the ventral mldbram and the ventral part of the rostral pons The optic nerves did not appear to be affected Brains of the other 7 rats appeared normal RESULTS Table 3 summarizes the results of the radial maze tests with varymg delays imposed between the 4th and 5th choices The old rats reqmred more sesstons to adapt to the maze, t(20)=6 7 1 , p < 0 001, and to reach criterion at 0 delay and at the 5 hr delay (ts>2 37, p s < 0 05) The difference between the young and old groups on this measure was not slgmficant at the 1 hr delay (t = 1 03) The old rats made significantly more errors m reaching c n t e n o n at the 5 hr delay (Mean--76 3 vs 30 5, t(20)--2 3 9 , p < 0 05), but differences on errors to criterion at the shorter delays were not rehable (Means=34 0 vs 24 0 for 0 and 23 0 vs 15 8 for l hr, t s < l 22) The rat with the pRu~tary adenoma reqmred 25 sessions and made 61 errors in meeting criterion at 0 delay It reqmred 5 sessions and made 4 errors at 1 hr delay It made 266 errors and d~d not meet criterion at 5 hr delay Furthermore at 5 hr, it often made errors d u n n g the first 4 choices and repeated v,s~ts to arms already entered d u n n g the retentzon tests Other animals almost never made these kinds of errors Hence we assume that the pituitary adenoma became manifest d u n n g the 5 hr tests If this rat's data at this delay are discarded, the remmnmg 7 old rats averaged 22 6 sessions and 49 4 errors to c n t e n o n , but differences between the old and young groups remmned rehable on both measures (both p < 0 05) DISCUSSION In agreement wtth several other studies employing cross sectional designs [6, 27, 29], aged rats acqmred accurate per-

AGING AND SPATIAL MEMORY

223 TABLE3

R A ~ A L MAZE PERFORMANCE OF YOUNG AND OLD RATS IN E ~ E ~ M E N T 2

Acquisition Measures

Postcntenon Performance

Mean Sessions to Criterion*

Mean Percent Correct (Choices 5-8)*

Adapt to Maze

0

Delay (hr) 1

5

0

Delay (hr) 1

5

Young

26 (0 4)

15 4 (1 8)

10 9 (20)

12 0 (20)

85 6 (2 3)

81 9 (1 6)

81 8 (2 9)

Old

86 (0 9)

24 4 (3 l)

15 1 (4 I)

26 0 (7 1)

87 5 (3 O)

88 3 (2 7)

80 8? (4 7)

*Numbers m parentheses are the SEM ? N = 6 , 2 old rats did not meet c n t e n o n at 5 hr delay

formance on the radial maze more slowly than younger animals The lack of impairment m acqmsRlon at the 1 hr delay or on any of the p o s t c n t e n a l tests makes ~t most unlikely that sensory deficits or lack of motivation are responsible for the deficient performance by the old rats One posslblble explanation for the remarkable preservation of spatml memory displayed by our old rats relates to their long history of food deprivation that necessarily accompanied their extended testing Restricted feeding reduces body weight and prolongs life in rats [25] and a regimen of feeding every other day eliminated the impaarment in acquisition of a multiple unit maze usually observed m freely fed old rats [24] Whether or not the food deprlvah,**, reg,men used In the present study would confer similar prophylacuc effects is unknown, but this nutrmonal status variable merits attention m future studies In our original demonstration of the longevity of accurate spatial memory in rats [19], we observed no decline in performance for delays of up to 4 hr when the length of the delay interval was gradually increased While ~t might appear from those data that accurate spatml memory over long retention intervals IS automaucally engaged once the subject acquires the win-shift rule at 0 delay, much subsequent experience [13, 21, 29, 35] indicates that this is not the case When a delay Is first inserted dunng the sessmn, performance on the retention test is typically above chance (e g , [35]), but well below its ultimate asymptote The acqmsRmn data for the young rats tested in Experiment 2 (cf Table 3) illustrate rather mcely th~s typical pattern suggesting that the lntroductmn of delays requires the rat to learn new rules (e g , removal from the maze need not s~gnal the end of a trial, Initial 4 arms chosen must be remembered for long p e n o d s of time, etc ) Old rats are clearly less able to master new rules rapidly, but once acquired they are able to use them as well as younger ammals From this perspective the superior performance displayed by the 26 month old rats in Experiment 1 is not at all surprising since they spent most o f their lives refining their skill at remembenng spatial locations over long temporal intervals That their performance remained very accurate despite 3 months without practice rinses the possibility that remembenng spatial locatmns accurately for a long time is a rodent analogue of certain cogmtive skills in humans that have been labelled "'crystalhzed intelligence" by some [3, 18, 34] However, the fact that these old animals were impmred in

learning a new spatial problem mandates caution or at least suggests that the cognitive skdls preserved are quite task specific Whether or not this analogy is appropnate both the amount of tralnmg required to preserve accurate spatial memory as well as the amount of ume without practice over which accurate memory can survive are mteresting, ff parametric, questions that can not be approached Once these questions are answered it may be possible to address the question of how the brain retains certain memories for a lifetime as it clearly does [1,2] Even if one regards the foregomg suggestion as brazen speculatmn the present findings have important Implicatmns for both the behavioral and neuroblological aspects o f a g m g Because deficits m spatial behavior are readily reproduced in aged rodents considerable effort has been devoted to estabhshlng biological correlates of these behavioral deficits F o r example, retention of the enhanced responsiveness after high frequency sUmulation o f the perforant pathway is dimlshled m aged rats [4] Agmg Is also associated with a loss of place specificity m the l~ppocampal complex spike ( " p l a c e " ) cells [5] Much attention ~as been directed at evaluating the posslbdity that pathological changes m the operation of cholmerglc circmts, especmlly those supplying the hippocampus and the cerebral cortex, may underlie age-related deficits In spatml " m e m o r y " [20, 27, 33] m particular and other forms o f memory m general [8, 9, 10, 28, 36] With respect t~, spatml memory the findmgs that scopolamine treatment m young rats impmrs a c q u i s i t i o n o f a c c u r a t e respondmg in the r a d i i maze [37] and mcreases WM error rates m well trmned subjects [40] are consistent with the chohnerglc hypothes~s, as m the demonstratmn that 3,4dIammopyndme, which sUmulates acetylchohne release, ~mproves radial maze performance m aged rats [20] By demonstratmg that the behaworal deficRs m the r a d i i maze assocmted with agmg are not immutable changes m the capacity to remember spatml mformauon, but instead reflect difficulties m acqmsRion than can be overcome by additmnal tramlng or prevented by prior experience on the task, the present findmgs wall hopefully direct attentmn at d~scovenng the physmlogtcal mechanisms by wl-ach experience affects these changes The ~dea that " m e m o r y " deficits in aged animals may more accurately be described as retarded acquIsmon which can be allewated by addmonal training and perhaps pre-

224

BEATTY, BIERLEY AND BOYD

v e n t e d by prior o v e r t r m n m g appears to be supported by data from tasks that are nonspattal m nature F o r e x a m p l e , old rats are m m a l l y ~mpmred m D R L tests b e c a u s e they respond p r e m a t u r e l y but wRh add~tmnai training they m m n t a m perf o r m a n c e that ~s c o m p a r a b l e to that of young animals [26] Or c o n s i d e r m e m o r y for passive a v o i d a n c e training If a single training trial ~s g w e n , old rats r e m e m b e r as well as y o u n g e r animals for a few hours but at longer retention intervals (24-48 hr) their m e m o r i e s a p p e a r d e f e c t i v e [10, 12, 28, 31, 32, 41] H o w e v e r , if multiple tnals are given the aged ammals usually display no m e m o r y deficit [12] Clearly there are hmtts to the v i e w that m e m o r y deficits are the result o f i n c o m p l e t e acquisition In particular, defects m short-term m e m o r y (STM) o f old m o n k e y s described by Bartus and his colleagues [7, 8, 11] almost certainly reflect age-related deterioration o f S T M storage m e c h a n i s m This ts

likely because m a n y of these ammals had thousands of trials on S T M p r o b l e m s and continued to exhibit reliable deficits m retention throughout their lifetime H o w e v e r , by reveahng that aged rats can display highly a c c u r a t e spatial m e m o r y , the present findings indicate that a more careful search for the memorial capacities that are p r e s e r v e d as well as a description o f those facultms that are degraded wdl yield important mformation for understanding the neuroblology of aging

ACKNOWLEDGEMENTS Partmlly supported by NSF grant BNS-8201448 We thank Gad Bergmskl and Khanh Tran who assisted m testing the animals and Lynnae Johnson for preparation of the manuscript

REFERENCES 1 Bahnck, H P The cognmve map of a city fifty years of learnmg and memory In The Psychology of Learmng and Motwatlon, edRed by G H Bower New York Academic Press, 1983 2 Bahnck, H P , P O Bahnck and R P Wlttmger Fifty years of memory for names and faces A cross-sectional approach J Exp Psychol Gen 104 54-75, 1975 3 Baltes, P B and K W Schme On the plasticity of lntelhgence In adulthood and old age Am Psychol 32" 369--373, 1976 4 Barnes, C A Memory deficits associated with senescence A neuro physiological and behavioral study in the rat J Comp Physlol Psychol 93" 74-104, 1979 5 Barnes, C A , B L McNaughton and J O'Keefe Loss of place specificity m bappocampal complex spike cells of senescent rat Neuro&ol Aging 4. 113-119, 1983 6 Barnes, C A , L Nadel and W K Homg Spatial memory deficit m senescent rats Can J Psvchol 34: 2%39, 1980 7 Bartus, R T Effects of aging on visual memory, sensory processing, and dlscnmmatlve learning in a nonhuman pnmate In Sensor5' Systems and Commumc attons tn the Elderly, edited by J M Orday and K Bnzzee New York Raven Press, 1979 8 Bartus, R T , R L Dean and B Beer Memory deficits m aged cebus monkeys and faclhtation with central chohnomimetlcs Neuro&ol Aging 1: 145-152, 1980 9 Bartus, R T , R L D e a n l I I , B Beer, a n d A S Lippa The chohnerg~c hypothesis of geriatric memory dysfunction Sc:ence 217: 408-417, 1982 10 Bartus, R T , R L Dean, J A G o a s a n d A S Lippas Agerelated changes m passive avoidance retention Modulation with dietary chohne Science 209. 301-303, 1980 11 Bartus, R T , D Fleming and H R Johnson Agang m the rhesus monkey Debdltatang effects on short-term memory J Gerontol 33: 858-871, 1978 12 Bartus, R T , C Fhckerand R L Dean Logical pnnclples for the development of animal models of age-related memory impa~rments In Assessment m Geriatric Psychopharmacologv, edRed by T Crook, S Ferns and R Bartus New Canaan, CT Mark Powley A s s o c , 1983 i 3 Beatty, W W Opiate antagonists, morplune and spatial memory m rats Pharmacol Biochem Behav 19" 397-403, 1983 14 Beatty, W W , K R Bengtson, R J Lunn, R D Staton and R A Brumback Comparauve effects of long-term ethanol consumption and forebrmn lesions on maze learning and active avoidance behavior m rats Alcohol, in press 15 Beatty, W W and J R Rush Spataal workmg memory m rats Effects of monoammerglc antagonists Pharmacol B~ochem Behav lg: %12, 1983 16 Beatty, W W and J R Rush Retention deficit after d-amphetamine treatment Memory defect of performance change '~ Behav Neural BJol 37: 265-275, 1983

17 Beatty, W W and D A Shavalla Spatial memory m rats Time course of working memory and effect of anesthetics Behav Neural Bwl 28. 454-462, 1980 18 Cattell, R B Theory of fluid and crystalhzed intelligence A crlUcal expenment J Edu~ Psvc hol 54 1-22, 1963 19 Cralk, F I M Age differences m human memory In Handbook of the Psychology of Agmg, edited by J E Birren and K W Schale New York Van Nostrand Rhemhold, 1977 20 Davis, H P , A Idowu and G E Gibson Improvement of 8-arm maze performance m aged Fisher rats w~th 3,4dlammopyndme Exp Aging Res 9. 24--213, 1983 21 Goddmg, P R , J R Rush and W W Beatty Scopolamine does not disrupt spatial working memory in rats Pharmacol Btochem Behav 16" 91%923, 1982 22 Goodnck, C L Learning, retention and extinction of a complex maze habit for mature-young and senescent Wlstar albino rats J Gerontol 23. 298-304, 1968 23 Goodnck, C L Behavioral rigidity as a mechamsm for facdltatlon of problem solving for aged rats J Gerontol 30" 181-184, 1975 24 Goodnck, C L Effects of lifelong restricted feeding on complex maze performance in rats Age Ageing 7. 1-2, 1984 25 Goodnck, C L , D K Ingram, M A Reynolds, J R Freeman and N L Cider Differential effects of intermittent feeding and voluntary exercise on body weight and hfespan in adult rats J Gerontol 38" 36--45, 1983 26 Hamm, R J , J S K m s e l y a n d C E Dixon An animal model of age changes m short-term memory The DRL schedule Exp Aging Res 9: 23--25, 1983 27 lngram, D K , E D London and C L Goodnck Age and neurochemical correlates of radial maze performance in rats Neurobtol Aging 2: 41--47. 1981 28 Kubanls, P and S F Zornetzer Age-related behavioral and neurobiologmal changes A review with emphasis on memory Behav Neural Btol 31 115-172, 1981 29 Makl, W S , W W Beatty, N Hoffman, R A BierleyandB A Clouse Spatial memory over long retentmn intervals Nonmemorial factors are not necessary for accurate performance on the radml-arm maze by rats Beha~ Neural Btol 41 1--6, 1984 30 Markowska, A , O Buresova and J Bures An attempt to account for controversial estimates of working memory persistence m the radial maze Behat Neural Btol 38 97-112, 1983 31 McNamara, M C , G Begmgnus, V A Begnignus and A T Miller, Jr Active and passive avoidance m rats as a function of age Exp Aging Res 3. 3--16, 1977 32 Messing, R B , H Rigter and V Nickolson Memory consohdation m senescence Effects of CO2, amphetamine and morphine Neurobtol Aging 3 133--139, 1982

AGING AND SPATIAL MEMORY

33 Segal. M Changes m neurotransmttter actions tn the aged rat htppocampus Neurablol Aging 3" 121-124. 1982 34 Schale. K W a n d C Hertzog Fourteen-yearcohort-sequent,al analysts of adult mtellectual development Dev Psvch¢,l 19 531-543. 1983 35 Shavaha. D A . A M Dodge and W W Beatty Timedependent effects of ECS on spattal memory m rats Behav Neural Btol 31 261-273. 1981 36 Sherman. K A . J E Kuster. R L Dean. R T B a r t u s a n d E Fnedman Presynapt,c cholmerg~c mechanisms m brain of aged rats with memory impairments Neurobtol Aging 2 99-104. 1981 37 Stevens. R Scopolamine tmpalrs spatial maze performance m rats Phxs:~l Behav 27 385-386. 1981

225

38 Strong, R , P Hicks, L Hsu, R T Bartus and S J Enna Age-related changes m rodent brain chohnergtc system and behavior Neuroblol Aging 1" 59--63, 1980 39 Wallace, J E , E E Krauter and B A Campbell Ammal models ofdechnmg memory in the aged Short-term and spattal memory m the aged rat J Ger¢mt¢~l 35 355-363, 1980 40 Wirschmg. B A , R J Bemnger, K Jhamandas. R J Blegman and S R EI-Defrawy Differential effects of scopolamine on working and reference memory of rats m the radial and reference memory of rats m the radial maze Pharmac ol Btot hem Beha~ m press 41 Zornetzer, S F , R Thompson and J Rogers Rapid foregettmg in aged rats Behav Neural B.~I 36. 49--60, 1982