Physiological Psychology1976. 1'01.4 (1).1-10

Stereotaxic mapping of brainstem areascritical for memory of visual discrimination habits

in the rat

ROBERT THOMPSONLouisiana State University, Baton Rouge, Louisiana 70803

An attempt was made to map those pathways of the brain that are necessary for the performance ofvisual discrimination habits . This was accomplished by damaging different parts of the brain in previouslytrained rats and subsequently testing for retention. The map was constructed by plotting those areas ofthe brain damaged in rats showing a serious loss in retention. The resulting map could be separated into aspecific (visual) division consisting of the lateral geniculate nuclei, occipital cortex, and lateral half of thecerebral peduncle at nigrallevels, and a nonspecific division. Clearly represented within the latter werethe ascending fiber systems associated with both the brainstem reticular formation and the substantianigra.

With the use of the lesion method, it is possible tomap anatomical pathways of the brain that arenecessary for the memory (expression) of a learnedresponse. This can be accomplished by canvassingmany different cortical and subcortical areas withlesions (using. of course , different subjects fordifferent lesion placements) and subsequently testingthe subject's retention of a previously learnedresponse . The distribution of individual lesions foundto induce serious amnestic effects would delineatethose pathways which are relevant (either directly orindirectly) for the normal expression of that learnedresponse .

For the past 15 years, my associates and I have beenusing the foregoing method to map those regions ofthe brain which are essential for the memory ofpreviously learned visual discrimination habits in thewhite rat. Summaries of some of these results haveperiodically been published (Thompson, 1963, 1969;Thompson & Massopust , 1960; Thompson & Thorne,1973). and, in each case, the brain regions underinvestigation were broadened and the critical areasmore precisely defined.

In the current paper, a detailed description of thecritical brainstem (and telencephalic) areas for visualdiscrimination performance will be given in the formof a stereotaxic map. The data from which the mapwas constructed were derived from over 500brain-damaged rats and gathered in the periodbetween 1965 and 1975. The data on approximatelyhalf of these sub jects were briefly reported in earlierpapers scattered throughout the literature.

This research was supported in part by a grant from theGr aduate Council on Research . Louisiana State University.

MATERIALS ANDMETHODS

Adult male albino rats of the Wistar strain were used. Thesesubject s were trained on either a brightness discrimination(approach a white card and avoid an adjacent black or dark graycard) . a pattern discrimination (approach a horizontally black andwhite striped card and avoid an adjacent vertically black and whitestriped card) . or both . Following learning. most of the subjects weresubjected to bilateral one-stage cortical or subcortical lesions underdeep chloral hydrate anesthesia. In some cases . surgical braindamage was performed in two stages (unilateral lesion followed by acontralateral lesion) with an interoperative period of 10 to 15 days.Destruction of neocortical. cingulate, or cerebellar areas wasaccompli shed by the aspiration method . All other lesions weremade stereota xically with reference to the rat atla s of Massopust(1901). Depend ing upon the area to be destroyed . a constant anodalcurrent of 2-5 rnA was passed for 5-15 sec through an implantedstainless steel electrode with 1.0-2.0 mm of the tip exposed . Threetypes of electrocoagulative lesions were made. Type I lesionconsisted of a single insertion of the electrode into the brainfollowed by the application of current. This type of lesion was madeto destroy structures at the midline . such as the interpeduncularnucleus and the raphe nuclei . Type II lesion consisted of typicalbilate ral destruction of a nucleus or tract involving the insertion ofthe electrode on one side to produce a lesion. and then repeating theprocedure on the contralateral side. Type III lesion consisted ofmultiple insertions of the electrode on each side for the purpose ofenlarg ing the overall size of the lesion. Following a recovery period(or rest period in the case of the normal controls) of 2 to 3 weeks. allrat s were required to relearn the problem (problems) masteredpreoperatively. At the conclusion of the relearning test. eachbrain-damaged animal was sacrificed with an overdose ofNembutal. its vascular system perfused with normal saline followedby 10% Formalin. and the brain removed and stored in 100/0Formalin for 2 days . For cortical injuries . the lesion wasreconstructed on Lashley-type brain diagrams prior to sectioning.With a freezing microtome . each brain was sectioned frontally at90 microns in the stereot axic plane of Massopust (\%\) . Everythird section showing the lesion was photographed at IOX-14X bythe method of Gusman-Flores. Alcaraz . and Fernandez-Guardiola(\ 958). These photographs of unstained sections yielddifferentiation of the brain field similar to that obtained with a fiberstain (see Figures 1-5) and readily permit identification of the threemajor zones of the lesion-the vacuolated area. the narrow rim ofseverely coagu lated tissue . and the surrounding gliosis.

THOMPSON

Table IMean Savings Scores for All Groups and Percentage of Rats from Each Group Earning Zero or Negative Savings Scores

Percentage RatsLesion Mean Earning Zero or

Group N Type Savings Negative Savings

Control 90 95 .2 0Anterior neocortex 9 Suction 80.3 0Posterior neocortex 8 Suction - 83.0 75 .0Cingulate cortex 4 Suction 61.2 0Infralimbic cortex 3 Suction 95.0 0Rostral caudoputamen 6 III 70.3 0Caudal caudoputamen 3 III 20.0 33.3Globus pallidus 6 III -1.5 50 .0Entopeduncular area 8 II - 15.2 62 .5Septal area 6 II 98 .3 0:-J. accurnbens septi 3 II 91.0 0Amygdaloid area 5 III 93.4 0Dorsal hippocampus 7 III 74.3 0Hypothalamus

Ant eromedial 4 II 100 0Posteromedial 9 II 88.0 0Anterolateral 11 II 94 .5 0Posterolateral 10 II 1.9 50 .0

ThalamusAnterior 6 III 81.8 0Lateral 5 II 75.5 0Ventral 9 II 80.0 0Dorsomedial 8 II 85.1 0Ven tromedial 6 II 75.5 0N. parafascicularis 6 II 19.7 50.0N. posterior 12 II 18.7 41.7Lateral geniculate 2 II -90.0 100Medial geniculate 9 II 84.2 0

Subthalamic nucleus 7 II - 94.4 42 .9Zona incerta 5 II 75.0 0Pretectal area 10 II 24.0 40 .0Superior colliculus 8 III 63.5 0Inferior colliculus 6 III 80.2 0Subcollicular area 7 III 97.1 0Central gray 6 II 83.3 0Ventral tegmentum 9 II -6.7 44.4Substantia nigra 21 II - 3.1 52.4Lateral cerebral peduncle 13 III - 24.2 53.8Red n. 10 II -44.4 70.0Rostral interpeduncular n. 10 I 78.6 0Caud al interpeduncular n. 5 I 10.0 40 .0Rostral central tegmentum 10 I 80.0 0N. medianus raphes 10 I -5.8 50 .0Midbrain reticular formation

Rostral 21 II - 10.5 47 .6Suprarubral 5 II 90.0 0Supranigral 6 II 70.5 0Ventrolateral 14 II 25.7 35.7Caudal 13 II -2.0 46 .2

Lateral midbrain lemniscal area 10 II 91.0 0Pontine reticular formation II II -16.4 72.7Lateral pontine lemniscal area 10 II 89.9 0Cerebellum 3 Suction 71.3 0

The two-choice d iscrirnmation apparatus and related trammgprocedures have already been described (Thompson. 1%9). Briefly.unde r the motive of escape from (or avoidance 00 footshock, eachra t \\ as tr ained to approach the positive stimulus card (white in thec." e of the brightness problem and horizontal stripes in the case ofthe patt ern prob lem) and avoid the adjacent negative stimulus card ...\ revponse to the unlock ed posit ive card (correct response)admitted the rat 10 the goalb ox, wherea s a response to the lockedneuau ve card terror. was followed bv the automatic adm inistrationor mild tootvhock . EIght tr ials were given dailv with an intertrial

interval of 00 sec . Fifteen correct responses within 2 consecutivedays constituted the criterion of learning.

The retention test. which consisted of relearning the problem(problemvi . utilized the same procedures as those involved inoriginal learning . The retention measure was expressed in terms ofpercentage error savings which relates the indiv idual relearningscore with the corresponding origina l learning score.

In term s of savings scores. three general outcomes are possible .First. the brain-damaged anim al may relearn the problem about asfast as the normal controls and . as a consequence . achieve a high

Flgure 1. Photographs of lUIStained IedlOIl8 derived from threerata showing bUaterailesloll8 within the rostral caudoputamen (A),amygdala (B), and subcolUcuiar area (C). (All three rata earnedpositive savings seores.)

positive savings score (80% of the 90 control rats earned savingsscores in excess of 90%). Second . the brain-damaged animal mayshow some transient difficulty in regaining the habit . but willrelearn at a faster rate than in original learning. In this case. thesavings score will be lower than that associated with the firstoutcome, but still positive . Finally, the brain-damaged animal mayshow an enduring disturbance in reaching the criterion to the extentthat the problem is relearned at a slower rate (or at the same rate) incomparison to original learning. In this instance. the"savings . scorewill be zero or negative. Since the poorest control rat earned apositive savings score (30%), there is little doubt that zero ornegative savings reflects a serious loss in the expression of thepreviousl y learned visual discrimination problem. Therefore. it wasdecided that the critical areas for visual discrimination deficits willbe defined as those brain structures damaged in rats achieving zeroor negative savings scores.

Mapping the critical subcortical areas was done in the followingmanner. For each rat . the photograph of the brain section throughthe "center" of the lesion was selected . The central necrotic zone ofthe lesion (the vacuolated and severely coagulated areas) was thenreconstructed on the right side of a frontal section derived from theMassopust (1961) atlas- that most closely corresponded to thefrontal level shown in the photograph. If the rat earned zero ornegative savings . the central necrotic zone of the lesion was alsoreconstructed on the left side of the same corresponding section.

The specific naming of structures and tracts within the textfollowed the international convention of nomenclature and wasguided by the rat atlas of Skinner (1971).

RESULTS

General FindingsTable 1 presents the mean savings scores for alI

BRAINSTEM AND MEMORY 3

groups and the percentage of rats from each groupthat earned zero or negative savings. (In those caseswhere the animal earned two savings scores--one forthe brightness problem and one for the patternproblem-only the lowest savings score wasconsidered) . It will be noted that only 20 of the 49brain-damaged groups contained animals earningzero or negative savings.

Figures 1 and 2 show subcortical lesions in six ratsderived from groups that did not contain any animalsearning zero or negative savings . Figures 3, 4, and 5show subcortical lesions in 11 rats that earnednegative savings.

In all subsequent figures describing the results,those areas of the brain convassed with lesions areshown in stipples on the right side of each section (ordiagram). The left side of each section shows thecomposite areas of the brain damaged (large blackdots) in those rats that failed to earn a positive savingsscore. For convenience , the combined critical areasmarked with black dots will be termed the " visualdiscrimination memory system" (VDMS).

Neocortex and cerebeUum. As shown in Table 1and Figures 6A, 6B, and 6C, ablations of the occipitalareas caused serious retention disturbances (thus , theoccipital cortex is a component of the VDMS), while

Flgure 2. Photographs of Ull8talned 1edl01l8 derived from threerata showing bUateral lesloll8 within the anterior thalamus (A),dorsal hippocampus (B), and ventral thalamus (C). (AD three rataearned positive savings scores.)

4 THOMPSON

Flgure 3. Photographs of W1Stained lleCtions derived from threerats showing bUateral lesloDS wltbln the globus pailidus (A),entopeduncular area (B), and subthalamus (C). (All three ratsearned negative savings seores.)

Tsai, substantia nigra. medial lemniscus. lateral halfof the cerebral peduncle. and the ventral portions ofthe mesencephalic reticular formation (Figures 9Mand ION). At the dimesencephalic juncture (Figures9K and 9L). the VDMS appears to bifurcate, onebranch coursing dorsally toward the thalamus and theother maintaining a ventral course toward thehypothalamus and subthalamus . The posteriordiencephalic level shown in Figure 9J discloses thelargest extent of the VOMS in cross section, but just0.5 mm more anteriorly (Figure 91), the VDMSconstric ts to a small region in and around the medialportion of the cerebral peduncle, and maintains thisposition and size rostrally through the area of theentopeduncular nucleus (Figure 8H). Due toincomplete (or unsuccessful) canvassing of brainstructures at anterior diencephalic levels (Figures 8E,8F . and 8G). the VDMS does not make anappearance, but does reappear within the globuspallidus (Figure 70) and the caudal portions of thecaudate-putamen complex (Figure 7C). No furthertrace of the VDMS is seen at more rostral levels.

SummaryAs shown above. the VDMS consists of the caudal

half of the cerebrum (occipital areas) and a more orless continuous subcortical "pathway" of varyingbreadth extending from the pontine reticularformation to the corpus striatum. The only breakwithin this pathway occurs between the ento­peduncular area and the globu s pallidus.

It is conceivable that the internal capsule

Figure 4. Photographs of unstained sections derived from fourrats showing bilateral lesions wltbln the parafasclcular area (A),nucleus posterior (B), rostral midbrain reticular formation (C) , andred nucleus (D). (All four rats eamed negative savings seeees.)

ablations of the more anterior regions of the cerebrumdid not.

All three rats with virtually total destruction of thecerebellum achie ved positive savings scores.Therefore . the cerebellum is not a component of theVDMS.

Limbic forebrain areas. In no case did lesions of thecingulate cortex and /or infralimbic region (Fig­ure 6D), septal (Figures 7A, 78. and 7C), orseptoforn ix (Figure 7D) area , nucleus accumbenssepti (Figure 7A). hippocampus (Figures 28 and 8H) ,or amygdala (Figures 18 and 8H) lead to savingsscores below 25%.

Brainstem areas. Figures 7 to 10 summarize theresults on the canvassing of the brainstem. It will beseen that the most caudal extent of the VDMSoccupies the pontine reticular formation in regionscorresponding to the nucleus reticularis pontis oralis,nucleus reticularis tegmenti pontis, and the nucleusmedianus raphes (Figure lOR). At more rostral levels.the VDMS broadens to include the lateral and medialportions of the mesencephalic reticular formation(ventral portions of the nucleus cuneiformis), thecaudal half of the interpeduncular nucleu s. and theoverlying central tegmentum (Figure lOP). Furtherrostrally . th e VDMS shift s somewhat laterally toincorporate the red nucleu s. ventral tegmental area of

A B

constitutes the link in the VDMS pathway betweenthe entopeduncular area and the globus pallidus. Adozen rats sustaining bilateral two-stage lesionswithin the internal capsule all manifested seriousaphagic-adipsic disturbances and a profoundakinesia. which lasted until death (from 5 to 9 daysfollowing the second operation) . Three of these ratswere given a retention test on the brightness problemstarting on the fifth postsurgical day. and all showedno evidence of relearning. Due to the poor physicalhealth of these rats during the retention test . nodefinitive conclusions can be made . However. whenthese data are combined with the frequent observationthat the globus pallid us. internal capsule, andentopeduncular area are common sites through whichman y ascending and descending fiber systems traverse(Hedreen, 1971; Knook , 1966; Lynch , Smith. &Robertson, 1973; Morgane, 1961; Shimizu &Ohnishi, 1973; Ungerstedt. 1971). the possibility thatthe internal capsule is included within the VDMSmust be seriously considered .

DISCUSSION

Preliminary ConsiderationsAs far as can be determined , this is the first attempt

to use the lesion method to map pathways of the braincritical for the performance of a learned response andto present the results in stereotaxic form . It must beemphasized at the outset that the results of this study.like those of most other neuroanatomical andneurophysiological investigations. are intimately tied

Figure 5. Photographs of unstained sections derived from fourrats showing lesions within the substantia nigra (AJ, ventrolateralmidbrain reticular formation (B), Interpeduncular and raphe nuclei(0, and pontine reticular formation (D). (All four rats earnednegative savings scores.)

BRAINSTEM ANDMEMORY 5

Figure 6. Schematic drawings of the dorsal (B) and lateral (A, Clsurface of the cerebral cortex and a parasaglttal section (D) of therat brain. (Stippled areas Indicate the composite of lesionplacements Investigated. Areas covered by large black dots Indicatecomposite of lesion placements leading to zero or negative savingsseores.)

to the methodology used . It is conceivable thatincreasing the size of the lesions investigated.exclusively using two-stage surgical procedures .lengthening the recovery period. using a differentkind of discrimination apparatus. administering alarge number of overlearning trials prior to surgery.varying the previous experience and /or age of thesubject . or establishing a different set of criteria forthe determination of a "serious amnestic distur­bance" might alter the composition and extent of theresulting map . Therefore. the VDMS mapped in thecurrent study must be viewed with these constraints inmind.

On the other hand. there are reasons to believe thatthe major portion of the VDMS may be invariant overa wide range of conditions. For example, negativesavings scores were obtained in some rats sustainingeither occipital. pallidal. posterior thalamic . rubral,nigral , or ventral tegmental lesions whether or not thelesions were performed in one or two stages .Furthermore. except for two subcortical areas. thecharacter of the VDMS would be the same if onlythose brain-damaged rats trained on the brightness(or the pattern) discrimination were selected for theconstruction of the map. 2 Perhaps the most persuasivefinding is that virtually all of the critical subcorticalareas shown in Figures 7-10 (except for the lateralgeniculate nuclei and the lateral half of the cerebralpeduncle) have recently been demonstrated to benecessary for the expression of latch box problems , anonvisual discrimination problem. a conditioned

b THOMPSON

It sho uld be ap pare nt that the pa ttern of resu ltsobtained in this study are inexplicable in terms of a" mass action " effect- the size of the lesionindepen dent of its ana tomica l locus determines themagnit ude of the be haviora l deficit (Lashley. 1929).Those an ima ls having lesions of the rostra lca udoputame n (Fig ure IA). hippocamp us (Fig ­ure 2B>. ante rior tha lamus (Figure 2A). or dorsalmid brain (Figu re 10 . for exa mple. sustai ned at leasttwice as much dam age to neural tissue as th ose havingento peduncular (Figure 3B). su bt ha lamic (F ig­ure 30. posterior th alam ic (Figures 4A and 4B).ventra l mesencepha lic (Figures 4C, 40. SA. an d SB),or pontine reticul ar formation (Figure SO) lesions.Yet, the former brain-damaged anima ls fai led to showserious rete ntion deficits, while the latter . in ma nycases . ea rne d negati ve savings scores . Furtherevidence of th e importance of " lesion locus " ratherth an " lesion size" in determining the loss of visua ldiscrim inat ion hab its in th e rat may be found inexperime nts on the cere bral cor tex (Horel, Bett inger .Royce. & Meyer. 1966 ; Lash ley. 1929) . poster iortha lamus (Thompso n. Luk aszewska , Sch weigerdt , &McNew, 1967). ventra l midbrain (Craddock &Thompson . 1971; McN ew. 1968). and br ain stemret icular form ati on (Petit & Thompson. 1974;Th omp son & Th orne. 1973).

Figure 8. Frontal sections at successive levels of the brainstem(See Figure 7 for description.)

Functional Divisions of the VDMSThe VOMS may be separated into two major

functional divisions : a "specific" (visual) divisi on .

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Figure 7. Frontal sections at successive levels of the brainstemare based upon the Massopust (1961) stereotaxic atlas and thecorresponding coordinates (In mllUmeters) rostral to theInteraurlcular line are given below each section. (Those ~as of thebrain canvassed with lesions are shown In stipples on the right sideof each section, while those areas of the brain damaged In ratsearning zero or negative savings scores are shown as large blackdots on the left side of eacb section. Abbrevtatlonss AC = anteriorcommissure; AM = amygdala; AT = anterior thalamus; BC =brachium conjunctlvum; CG = central gray; CI = inferiorcoliiculus; CP = caudoputamen; DM = dorsomedlal tbalamus;EP = entopeduncular nucleus; FX = fomlx column; GL = lateralgeniculate nucleus, pars dorsalis; GM = medial geniculatenucleus; GP = globus pallldus; H = habenula; HC =hippocampus; HP = habenulopeduncular tract; IC = Internalcapsule; IP = Interpeduncular nucleus; L = lateral thalamus; LH= lateral hypothalamic area; LM = medial lemniscus; MB =mamlllary bodies ; MRF = midbrain reticular formation; MT =mamlllo-thalamic tract; NAS = nucleus accumbens septl ; NP =nucleus posterior; OC = optic chiasma; PF = parafasclcularnucleus; PP = cerebral peduncle; PRF = pontine reticularformation; RN = red nucleus; S = septal area; SC = superiorcoiliculus; SN = substantia nigra; ST = subthalamic nucleus; V =ventral thalamus; VM = ventromedial thalamus; VT = ventraltegmental area.)

avoidance response. and a maze hab it (seeThompso n. 1974).

On the ba sis of th e foregoing dat a . it is reason ableto expec t th at th e ana tomic al limits of th e VDMSmapped in th e current st udy will not be dis turbingl yca pricious from one rep licat ion to the next. In fac t.the seco nd attempt to map the VDMS in 1963 yieldedresu lts which bear a strikin g resemblan ce to th oseprese nted in th e cur rent st udy (Thompson. 1963).

consisting of the occipital cortex, lateral geniculatenuclei. and the lateral half of the cerebral peduncle atnigral levels, and a "nonspecific" division, containingthe remaining components of the VDMS .

As shown in earlier studies, lesions damaging eitherthe occipital cortex (Thompson, Malin . & Hawkins,19(1) or the lateral half of the cerebral peduncle(Thompson & Craddock, 1972) do not seriouslyimpair retention of a nonvisual (incline plane)discrimination habit. In contrast. lesions damaginganyone of the remaining (nonspecific) components ofthe VDMS drastically impair retention of a nonvisualdiscrimination habit? and other habits as well<Thompson. 1974).

In the light of the foregoing findings, it would beappropriate to discuss each division separately .

Specific division of the VDMS. It is well establishedthat the retino-geniculo-occipital pathway functionsspecitically in visually guided behaviors and thatlesions placed anywhere along this pathway willdisrupt the execution of visual discrimination habits(Lashley , 1929, 1935.1950). On the other hand, thereis no general consensus about the pathways beyondthe occipital cortex that support visual discriminationhabits (Geshwind , 1965; Lashley, 1950; Mishkin ,1966; Myers , 1965; Pribram , Spinelli, & Reitz . 1969;Thompson, 19(5).

The tinding that lesions of the lateral half of thecerebral peduncle hinder learning and retention ofvisual discrimination habits, while having little or no

Flgure 9. Frontal sections at snccesslve levels of the bralnstem.(See Figure 7 for description.)

BRAINSTEM AND MEMORY 7

Flgure 10. Frontal sections at successive levels of the bralnstem.(See Figure 7 for description.)

effect on learning and retention of a nonvisualdiscrimination habit (Howze, 1974; Thompson &Craddock, 1972). provides a possible clue for theresolution of this important problem. at least withrespect to the rat. The lateralmost portion of thecerebral peduncle in the rat is known to containoccipitofugal fibers en route to the brainsetm (Knook,1966; Krieg, 1947; Nauta & Bucher, 1954; Valverde,19(2), and one investigator (Valverde . 19(2) hasobserved some of these fibers terminating within thenucleus cuneiformis and the nucleus reticularis pontisoralis . Since the latter two reticular regions areincluded within the nonspecific division of the VDMS,the possibility exists that visual discrimination habitsare mediated by a retino-geniculo-occipito-reticularpathway. Some support for this possibility hasrecently come from studies examining retention ofvisual discrimination habits in rats sustainingunilateral damage to the occipital cortex andcontralateral damage to the nucleus cuneiformis(Petit & Thompson. 1974). If subsequent anatomicalinvestigations confirm the existence of occipito­reticular projections, then there would be grounds forreexamining the notions of Penfield (1954) concerningthe presence of a centrencephalic mechanism withinthe brainstem which serves to coordinate andintegrate the activities of the cerebral hemispheres.

8 THOMPSON

Nonspecific division of the VDMS. This division(N-VDMS) is extensively represented throughoutmost of the neuraxis investigated, covering brainstemstructures ranging from the pontine reticularformat ion to the corpus striatum. The veryextensiveness of this division forbids any detailedanalysis of all possible pathways contained therein.However, two major ascending fiber systems areclearly recognizable within the N-VDMS andprobably contribute in a very important way to theperformance of visual discrimination habits .

One of these is the ascending brainstem reticularsystem. The correspondence between the N-VDMSand the trajectory of the ascending reticular fibers asdescribed by the Scheibels (1958) is conspicuous,particularly in connection with the bifurcation atposterior diencephalic levels. In a recent study byLynch. Smith, and Robertson (1973), using theNauta-Gygax and Fink-Heimer methods, ascendingpathways from the ponto-mesencephalic reticularformation have been described which coincide evenmore remarkably with the major portions of theN-VDMS. Specifically, they traced fibers passingthrough or near the brachium conjunctivum(including a crossing component at or near thedecussation). traversing dorsal to the red nucleus, andthen bifurcating at posterior diencephalic levels, onebranch projecting to the pretectum and thalamus andthe second coursing through the subthalamus,entering the internal capsule, and terminating within(or passing through) the ventral aspect of the corpusstriatum . As might be expected from the foregoingobservations , the ascending catecholaminergic(Lindvall & Bjorklund, 1974; Ungerstedt, 1971) andascending cholinergic (Shute & Lewis, 1%7) fibersystems associated with the brainstem reticularformation also pass through the major components ofthe N-VDMS.

The second major ascending fiber system whichappears to be represented within the N-VDMS has itsorigin within the substantia nigra and adjacenttegmentum . The nigro -striatal (dopaminergic)pathway , as described by Ungerstedt (1971) withhistotluorescence method and confirmed by Shimizuand Ohnishi (1973) with the Fink-Heimer method,passes through the ventral tegmental area, thencourses rostrally through the lateralmost portions ofthe medial forebrain bundle, enters the internalcapsule and globus pallidus, and subsequentlyramifies within the neostriatum. An even morestriking correspondence appears in relation to thepathways originating within the nondopaminergiccells of the substantia nigra. According to Hedreen(1971), these cells send their fibers not only to theneostriatum, but to the entopeduncular nucleus ,globus pallidus, posterior thalamus, and pontinereticular formation as well.

Other Functional ConsiderationsThere is little doubt that the performance of a

previously learned response constitutes a highlycomplex act on the part of the organism, requiring thesimultaneous engagement of many functional systemsof the brain. On these grounds alone, it can be arguedthat the VDMS is no more than a conglomerate ofdiscrete anatomical foci, each contributing in aspecialized way to the performance of visualdiscrimination habits. For example, one component(or group of components) would playa role in themotivational process, a second in the attentionalprocess, a third in the sensory-perceptual process, etc.

Clearly, the VDMS can readily be parceled into aspecific (visual) and a nonspecific division. Furtherfunctional parceling, particularly of the N-VDMS,may also be possible. At the same time , however, theremarkable degree of morphological continuity whichcharacterizes the N-VDMS suggests the presence of ahighly organized nervous substratum whose functionmay be more aptly expressed in terms of the dynamicinteractions between its constituent parts. In otherwords , the N-VDMS may constitute the "memorysystem" of the brain to the extent that it may containthose integrated circuits necessary for theadaptiveness of behavior especially retlected in theperformance of learned (and unlearned) responses(see Thompson & leDoux, 1974). Perhaps the mostpersuasive support of this notion comes from therecent neurophysiological studies of aids and hisassociates (Disterhoft & aids, 1972; aids, Disterhoft,Segal, Kornblith , & Hirsh, 1972) on the identificationof those units of the brain that exhibit " conditionedresponses" with the shortest latencies. Although these"learning units" were identified at various levels ofthe neuraxis, their distribution within the brainstemstrikingly coincides with the N-VDMS.

CONCLUSIONS

There has always been a need in the neurosciencesfor information showing a correspondence between abehavioral deficit and the destruction of a specificanatomical pathway within the brain. In the design ofmost lesion experiments focusing on such problems,the investigator constructs a specific hypothesisconcerning the functional significance of a specificpathway, and then proceeds to canvass that part ofthe brain with lesions. In contradistinction to thisapproach would be one in which no specifichypotheses are formulated and no discrete parts of thebrain singled out for investigation; virtually the entirebrain would be canvassed with lesions. Although thelatter approach is considerably more time-consuming,it ultimately provides a complete "functional" map ofthe brain for any given behavioral response fromwhich correspondences to known neuroanatomicalpathways can be inferred.

As demonstrated in the current study, it is feasibleto construct a functional map of the brain with the useof the lesion method even when the behavioralrespon se under investigation is a learned one. The

map for the express ion of pre viou sly learned visualdiscrimin ati on habits was found to be both extens iveand complex. but not abstruse . To illustrate . ananalysis of th e map disclosed the following : (a ) itappears to be composed of a specifi c division (lateralgeniculate nuclei. occipital cortex. and lat eral half ofthe cerebral peduncle at nigral levels) having visualfuncti ons and a nonspecific div ision having perhapsarousa l and integrati ve function s ; (b) clearl yrecogn izabl e within the nonspecitic division areascendi ng tiber systems associ ated with the brainstemreti cular formatio n and the substantia nigra ; and(c) the intermediary link between the two d ivisionsmay be prov ided by occipitoreticular projecti ons.

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10 THOMPSON

NOTES

I . It was necessary to extend the atlas at more rostral andcaudal levels in order to accommodate all of the data .

2. Lesions of the pretecta I area tend to produce greater losses onthe brightness problem than on the pattern problem. The oppositeeffect tends to occur in the presence of ventrolateral midbrainreticular formation lesions.

3. In a recently completed experiment by Thompson. Arabie.and Sisko the lesion method was used to map those brain areascritical for the expression of the incline plane discrimination habitin the white rat. Unlike the results on visual discrimination habits.the performance of the incline plane problem is dependent upon theintegrity of the parietal cortex . cingulate cortex. septal nuclei.anterior. ventromedial. lateral. and ventral thalamic nuclei. medial

longitudinal fasciculus. and the cerebellum. On the other hand. theincline plane discrimination habit is similar to visual discriminationhabits to the extent that it is abolished by lesions of eitherthe caudoputamen-pallidum complex. entopeduncular nucleus .posterolateral hypothalamus. subthalamus. posterior thalamus.ventral tegmental area. substantia nigra. red nucleus .interpedunculo-central tegmental area. midbrain reticularformat ion. or nucleus reticularis pont is oralis .

(Received for publication June 11. 1975;revision accepted July 9. 1975.)