142
Brain Re~eat~h, 95 (1975) 142 146 © Elsevier Scientific Pubhshmg (ompany, Amsterdam - Printed ~n The Netherland~
DRL performance following anteromedial cortical ablations in rats
CARL E ROSENKILDE* AND IVAN DIVAC Institute of Neurophyswlogy, Umver~tty oJ Copenhagen, Copenhagen (Denmark) (Accepted May 12th, 1975)
It was hypothesized that the anteromedml cortex m rats mediates behavior m tasks revolving spahal cues s or spatial choices 4 These notions are supported by reports of deficient performance following anteromedlal ablahons m delayed response s, delayed alternation ~2, spatial reversal 3 and spontaneous alternation 4 Such les]ons, however, also impaired performance of go-no-go alternation 2,v and actwe avoidangel3,21 The present study assessed whether the syndrome following Injury of the anteromedial cortex included impaired performance in a D R L situation Neither stlmuh nor responses are spatially differentiated in this situation and, as m delayed responsetype tasks, no actual exteroceptwe stlmuh control execution of responses Four naive male Wlstar rats weaghed lmtlally 303-448 g They were fed 40 mm after testing and maintained at 90 % of their ad hb body weight A two-lever Campden rodent test chamber (CI-410) with a pellet dispenser (CI-442) was enclosed m a sound attenuating box A ventilator provided masking home The left lever was used while the right lever was present but locked Reinforcement contingencies were controlled by standard translstonzed equipment from a separate room Rewards were 45 mg pellets locally produced from standard Rostock rat mtxture Prior to the experiment the rats were handled daily for 6 days After magazine training and shaping of bar pressing, the ammals received 150 pellets m daffy sessions under C R F conditions until m 2 successwe sessions they obtained all pellets in less than 15 mm The rats were then shifted to a D R L 10 schedule without hmlted hold Sessions of 40 rain were gaven 6 days a week until the rats attained an efficiency ratio (number of reinforcements/number of responses) of at least 50 % in each of 5 successwe sessions After a rest period of l0 days the rats were tested for retention for 5 sessions, subjected to surgery, and allowed l0 days recovery Testing continued on D R L l0 until the preoperative criterion was reattalned or for a maximum of 25 sessions The rats were operated on under clean condmons whde anesthetized w~th * Present address Section on Neuropsychology, Laboratory of Psychology and Psychopathology, National Institute of Mental Health, Bethesda, Md 20014, U S A
143 TABLE I SESSIONS TO C R I T E R I O N
Subject
Preoperattve a~qutsttton
Po~toperattve lelearmng
MFI MF2 M F3 MF4 Medmns
11 47 24 13 18 5
3 12 18 25 15
* Faded to reach crltermn In 25 sessions
E q m t h e s m (3 3 ml/kg), the a n t e r o m e d l a l cortex was removed by subplal aspiration with the use of a dissecting microscope Following c o m p l e t i o n of behavioral testing the deeply anesthetized animals were perfused with saline a n d 10% f o r m a l i n m saline Blocks of the brains were e m b e d d e d in 20°o gelatin a n d cut frozen at 100/~m Every 5th section was m o u n t e d a n d covered unstained The n u m b e r of sessions to reach criterion for individual rats before and after the operation is shown m Table I The performance o n D R L l0 deteriorated in all a m m a l s following anteromedlal cortical lesions (Table II) The lnterresponse times were more evenly distributed a n d m two cases the mode was changed to shorter intervals (Fig l) The cortical ablations are illustrated in Fig 2 The corpus callosum was slightly d a m a g e d m one rat N o relation was f o u n d between size or location of the lesIons a n d the i m p a i r m e n t s A n t e r o m e d l a l cortical damage in rats impaired r e t e n t i o n of a D R L schedule Previous studies of the effects of frontal lesions o n D R L indicated that ablations sparing the medial wall produced no deficit 17, but large damage caused variable degrees of I m p a i r m e n t ~1 N o r m a l rats a n d rats with a n t e r o m e d i a l lesions were tested on a c q u l s m o n of a D R L 20 schedule for 15 or 20 days 8,12, the absence of differences between the groups may be a t t r i b u t a b l e to insufficiently extended observation periods TABLE 11 RETENTION ON
DRL 10
Subject
Preoperattve retention* Efjh~teno' t atto
MF1 MF2 MF3 MF4 Medians
77 8 46 2 54 9 72 9 63 9
* Medians for 5 sessions
Postoperattve retentton*
Number o[ reinforcement s
Numbo oJ responae7
154 115 129 148 138 5
198 250 226 224 225
Eric tent)
Number o f
Number o]
latto
reinforce-
te~ponse5
ment~
43 0 39 1 31 2 35 7 37 4
122 110 84 94 102
284 281 269 263 275
144
60I~ 4O
I T1I I I I I I
0
W
~PRE-OP RETENTION o.--.o POST-OP RETENTION
Z 040 W20
I l l l l
O0
ITII
h140 (J {X h120 n
0
I
I
i
i
t
I I r I 0 2 4 6 8 10 12 14 16-->18 INTERRESPONSE TIME (sec) Fig 1 Medianinterresponsetime distnbut~onsfor individualanimalsduring 5 days of pre- and postoperativeretention Leverpressesat intervalsshorterthan 10sec werenot reinforced o
~!1410 ~IISO
~ttFOO
~Oqlil
~
O
~ 7 0 Fig 2 Reconstructionon standard dmgramsof the largest (horizontal stripes) and the smallest (black)lesions
145 T h e s e findings, t h e r e f o r e , m a y n o t be mcons~stent w~th the p r e s e n t o n e s a n d it m a y be c o n c l u d e d t h a t t h e a n t e r o m e d t a l c o r t e x a l s o s u b s e r v e s b e h a w o r m a s i t u a t i o n w h i c h ts n o t c h a r a c t e r i z e d by s p a t i a l l y d~fferenttated s t l m u h o r r e s p o n s e s T h e a n t e r o m e d m l c o r t e x o f t h e rat r e c e w e s t h a l a m t c p r o j e c t i o n s f r o m b o t h the medlodorsal and anteromedml
nuclei 5,9 C o n s e q u e n t l y ,
th~s c o r t i c a l a r e a m a y be
c o n s i d e r e d ' p r e f r o n t a l ' as well as ' c t n g u l a t e '15A6 a n d it m a y p o s s i b l y m e d m t e different functions
U n i t a r y e x p l a n a t i o n s o f all s y m p t o m s f o l l o w i n g a b l a t i o n s o f the a n t e r o -
m e d i a l c o r t e x m a y t h e r e f o r e be m i s l e a d i n g A comparatwe
analysis a c r o s s species m a y reveal ff the D R L deficit m the
p r e s e n t e x p e r i m e n t ~s a ' p r e f r o n t a l ' o r a ' c m g u l a t e ' s y m p t o m
T h u s m the m o n k e y
the m e d l o d o r s a l a n d a n t e r o m e d m l nuclei seem to p r o j e c t to s e p a r a t e c o r t i c a l fields 1 ~4 20,',~ A f t e r lateral p r e f r o n t a l lesions m m o n k e y s , b e h a v i o r u n d e r D R L c o n t i n g e n c i e s was d~sturbed 6, u n a f f e c t e d 1° 18 o r f a c d t t a t e d t'~, w h d e d a m a g e o f the o r b i t a l TM o r c m g u l a t e c o r t e x ~s d~d n o t interfere w~th D R L p e r f o r m a n c e T h e a v a d a b l e d a t a are e~ther t o o c o n f l i c t i n g or i n a d e q u a t e to a l l o w d e f i m t e c o n c l u s i o n s o n w h e t h e r p r e f r o n t a l or c m g u l a t e c o r t i c e s m m o n k e y s c o n t r i b u t e to D R L b e h a v i o r
T h e p r e s e n t results
suggest, h o w e v e r , t h a t th~s q u e s t i o n d e s e r v e s f u r t h e r i n v e s t i g a t i o n
1 AKERT, K , Comparative anatomy ol the frontal cortex and thalamocortlcal connections
2 3 4 5 6 7 8
9 I0
[I 12
13 14 15
16
In J M WARRENAND K AKERT (Eds), The Frontal Granular Cotte~ and Beha~lor, McGraw-Hall, New York, 1964, pp 372-396 BARKER, D J , AND THOMAS, G J , Effects of regional ablation of midhne cortex in alternation learning by rats, Phystol Behav, 1 (1966) 313-317 DIVAC, 1, Frontal lobe system and spatial reversal in the rat, Neto op~ychologta, 9 (1971) 175-183 DIVAC, I , WIKMARK, R G E , AND GADE, A , Spontaneous alternation in rats with les~ons in the frontal lobes an extension of the frontal lobe syndrome, Ph)~ol P s ~ h o l , 3 (1975) 39-42 DOMESlCK,V B, Thalamlc relationships of the medial cortex in the rat, Btam Beha~ E l o l , 6 (1972) 457-483 GLICKSTEIN, M QUIGLEY,W A , AND STEBBINS, W C , Effect of frontal and parietal lesions on timing behavior In monkeys, P~)chon S¢I, l (1964) 265 266 JOHNSTON, V S , HART, M , AND HOWELL, W , The nature of the medial wall deficit in the rat, Neut ops) chologla, 12 (1974) 497-503 KOLB, B , NONNEMAN, A J , AND SINGH, R K , Double dissociation of spatial impairments and perseveration following selective prefrontal lesions In rats, J comp ph~wol Pvv¢hol, 87 (1974) 772 780 LEONARD, C M , The prefrontal cortex of the rat I Cortical projection of the mediodorsal nucleus I1 Efferent connections, Bram Resealch, 12 (1969) 321-343 MANNING, F J , Performance under temporal schedules by monkeys with partial ablation of preI rontal cortex, Ph~ ~tol Behav, 11 (1973) 563-569 MFYER, M E , GRAY, C A , AND BLICK, C A , Effect of frontal ablations upon an acquired temporal discrimination, Psr~hon Sct, 13 (1968) 129-130 NONNEMAN, A J , VOIGT, J , AND KOLB, B E , Comparisons of behaworal effects of hlppocampal and prefrontal cortex lesions in the rat, J comp phvslol Psvchol, 87 0974) 249-260 PERETZ, E , The effects of lesions of the anterior cmgulate cortex on the behavior of the rat J tomp phvwol Pst¢hol , 53 (1960) 540-548 PRIBRAM K H , AND FULTON, F J , An experimental critique of the effects of anterior cmgulate ablations in monkey, Brain, 77 (1954) 34--~4 ROSE, J E , AND WOOLSEY, C N , The orbltofrontal cortex and Its connections with the mediodorsal nucleus in rabbit, sheep and cat, A~5 Res nerv ment Dis Proc, 27 (1948) 210-232 RosE, J E , AND WOOLSEY, C N , Structure and relations of hmbic cortex and anterior thalamlc nuclei in rabbit and cat, J comp Neurol, 89 (1948) 279-347
146 17 SCHMALTZ, L W , AND ISAACSON, R L , Effc~,ts of caudate and frontal lesions on retention and relearning of a DRL schedule, J ,omp physlol Psychol, 65 (1968) 343-348 18 STAMM, J S , Function of prefrontal cortex m timing behavior of monkeys, Exp Nemol~ 7 (1963) 87-97 19 STAMM, J S , Function of cmgulate and prefrontal cortex m frustratlve behawor, A cta Btol ,,~1~ (Warszawa), 24 (1964) 27-36 20 TOBIAS, T J , Afferents to prefrontal cortex from the thalamlc mediodorsal nucleus in the rhesus monkey, Brain Research, 83 (1975) 191-212 21 TRAFTON, C L , Effects of lesions in the septal area and cmgulate cortical areas on conddloned suppression of actJvlty and avoidance behavior in rats, J comp ph)swl Pswhol, 63 (1967) 191197 22 WIKMARK, R G E , DIVAC, I , AND WEISS, R , Retention of spatial delayed alternation m rats with lesions in the frontal lobes, Brain Behav Evol, 8 (1973) 329-339 23 YAKOVLEV,P J , LOCKE, S , KOSKOFF,D Y , AND PATTON, R A , Llmblc nuclei of thalamus and connections of hmblc cortex I Organization of the projecttons of the anterior group of nucle~ and of the mldhne nuclei of the thalamus to the antermr cmgulate gyrus and hippocampal rudiment in the monkey, Arch Neurol (Chw), 3 0960) 620-641