Perirhinal and Postrhinal Cortices of the Rat: a Review of the Neuroanatomical Literature and Comparison with Findings from the Monkey Brain

Home , Perirhinal cortex, Postrhinal cortex, Rat, Rhinal cortex, Rhinal sulcus

HIPPOWPUS 5:39&408 (1995)

COMMENTARY Perirhinal and Postrhinal Cortices of the Rat: A Review of the Neuroanatomical Literature and Comparison With Findings From the Monkey Brain

Rebecca D. Burwel1,l Mcnno P. Witter,* and David G. Amarall

‘Center for Behavioral Neuroscience, SUNY at Stony Brook, Stony Brook, New York. 2Department of Ana&wzy and Embryology, Research Institute of Neurosciences, Vrije Universiteit, Graduate School of Neurosciences Amsterdam, Anrsterdani, The Netherlands

KEY WORDS: polysensory cortex, memory, hippocampal formation, tinguish thc cortex situated caudal to these regions from parahippocampal, entorhinal the pre-striate cortex (areas 19 and 20). Von Bonin and Bailey (1947),however, noted that the cortex lying lateral to the hippocampus, in the parahippocampal gyms, was distinct from prestriate cortex and designated two areas, TF and TH, in this region. This review is prompted by recent findings that the perirhinal and What are these regions called in the rodent? Rose parahippocampal cortices in the monkey brain are important components (1 929) applied Brodmann’s terminology to the mouse of the medial temporal lobe memory system. Given the potential impor- brain and illustrated area 28, area 35, and area 36 (Fig. tance of the comparable rcgions 10 niemory function in rhe rat brain, it is LA). Rose did not further subdivide thcx cortical re- surprising that so little is known about their neuroanatomy. In fact, there gions, nor did he indicate a region that might be ho- are no comprehensive studies of the borders, cytoarchitecture, or connec- niologous to areas TF and TH. Krieg (1946b) also used tions of the cortical regions surrounding the posterior portion of the rhi- Brodniann’s numerical terminology in his cortical map nal sulciis in the rat. This review is meant to summarize the current state of the rat, although his boundaries differed substantially of our knowledge regarding these regions in the rat brain. Based on exist- from Rose’s, especially for areas 35 and 36 (Fig. 1B). ing data and our own observations, a new terminology is introduced that The entire region was located more caudally than in retains the term perirhinal cortex for the rostral portion of the region and Rose. This is because the rostrally adjacent area 13 (in- renames the caudal portion the posirhi!,indcortex. Issues of continuing un- sular cortex) extended Farther caudally, substantially be- certainty are highlighted, and information gleaned from the monkry liter- yond the caudal limit of the underlying claustrum. As ature is used to predict what anatomical traits thc rat perirhinal region in Rose’s nomenclaturc, Krieg did not indicate a sepa- might demonstrate upon further examination. To the extent possible with rate region homologous to TF and TH. More recently, available data, the similarities and differences of the rat and monkey perirhi- Deacon et al. (1 983) illustrated the perirhinal cortex in nal, postrhinal, and parahippocampal regions are evaluated. the rat essentially according to Krieg but nored that the cytoarchitectonic and connectional attributes differed along the rostrocaudal axis. This prompted them to subdivide the rostral porrion of perirhinal cortex and to riame [he more posterior portion the postrhinal cortex (Fig. 1C). Deacon et al. (1983) also illustrated a distinct Historically, Brodmann (1 909) illustrated three distinct cytoarchitec- ectorhinal cortex located dorsal to the postrhinal cortex. tonic regions near the rhinal sulcu, in primates: area 28 (area entor,’iinalis), Again, there was no explicit attempt on the part of area 35 (area perihnuli~),and area 36 (area ectarj7innli.r). He did not dis- Deacon et al. (1 983) to homologize either the postrhinal cortex or the ectorhinal cortex with :Jreas TF and TH in the monkey brain. Although these and othcr de- Accepted for publication July 51, 1995 Address correspondence and reprint requcctq to Kebecca D. Burwell, Ph.D., scriptions of the rat perirhinal region recognize distinct Centcr for Behavioral Neuroscience, SUNY at Stony Brook, 5tony Brook, perirhinal and ectorhinal cortices (areas 35 and 36, re- NY 11 794-2575 spectively), there has been no mention of cortex in the

0 I995 WILEY-LISS, INC. PERIRHINAL AND POSTRHINAL CORTICES OF THE RAT 391

A Rose, 1929 B Krieg, 1946 Dar 4

c Deacon, et al. , 1983 D Ziltes and Wree, 1985

E Paxinos and Watson, 1986 F Swanson, 1992 _. HI

FIGURE 1. A-F. Surface maps ofthe rodent cortex adapted from the region comparable to area 35 is shown in light gray. Note that six neuroanatomical reports cited in this commentary. Except for A, no region comparable to area 36 is indicated in the surface maps in which shows a surface map of the mouse brain, the maps show re- D and E. Essential abbreviations: Ecrh or Ec, ectorhinal cortex; Prh, gional definitions of the cortical mantle for the rat brain. For each perirhinal cortex; PRr and PRc, rostral and caudal perirhinal COT- map, the region comparable to area 36 is shown in dark gray, and tex; POr, postrhinal cortex.

rat brain similar to areas TF and TH in the monkey parahip- refers to both perirhinal and ecrorhinal cortices, and the term ec- pocampal gyrus. torhinal has largely been eliminated. Thus, Aniaral et al. (1987) Before moving on to a more detailed description of the posi- refer to the combination of areas 35 and 36 in the macaque mon- tion and borders of the various perirhinal regions, some additional key brain as the perirhinal cortex. The term parahippocampal has common usages of the terms perirhinal and parahipp~campal also had numerous usages. As noted above, parahippocampal should be addressed. In modern usage, the term perirhinal now refers to the gyrus in the macaque monkey that borders the hip- 392 BLIRWELL ETAL. pocampal formation. Amaral et al. (1987) have used the term pardhi[JpoCampal cortex to encompass areas TF and TH, which make up the larger portion of the parahippocampal gyrus. Rased on work carried out in the cat, but later applied to the rat and monkey brain, Wittcr et al. (1989a) used the term parahippocampal region as synonymous with retrohippocampal region As will become apparent, there is a remarkable lack of corn and included the entorhinal and perirhinal cortices, the pre- sensus regarding the boundaries and subdivisions of the regions subiculum and parasubiculum, and areas TF and 7'H. Van surrounding the rhinal sulcus in the rat (Figure 1). The position Hoesen (1982) used the term parahippocampal gyrus to reprc- and boundaries of the monkey perirhinal and parahippocampal sent cssentially the same regions as in the parahippocampal re- cortices are first summarized before continuing to the more con- gion of Witter et al. (198%) with the addition of primary olfac- tentious rat literature. tory cortex (area 51). According to this terminology, the In the monkey brain, the perirhinal cortex is laterally adjacent entorhinal cortex makes up the major portion of the anterior to the full rostrocaudal extent of thc rhinal sulcus (Fig. 2A). Arca parahippocampal gyrus, whereas areas TF and TH make up the 35 is a narrow band of agranular cortex situated primarily in the major portion of the posterior parahippocampal gyrus. Finally, fundus and lateral bank of the rhin;J sulcus (Suzuki and Arnaral, the term rhinal cortex was introduced by Murray and Mishkin 1994a). Area 36 is a larger strip of graiular cortcx located lateral (1986) to dcsignate thc region encompassing the entorhinal and to area 35 and bordered laterally by the unimodal visual area TE perirhinal cortices in the monkey. This term has also been used of inferotemporal cortex. Based on cytoarchitectonic and con- for this region in the rat (Mumby and Pinel, 1994). While these nectional grounds, Suzuki and Amaral (1994a) extended area 36 inclusive terms may be useful shorthand designations in lesion rostrally and dorsally to include the medial half of the temporal and behavioral studies, they can be misleading if taken to imply pole (area TG according to von Bonin and Bailey, 1947). These ncuroanatomical homogeneity. The entorhinal cortex, for exam- authors also described the border between area 36 and area TE ple, is distinctly different from the neighboring perirhinal and as occurring morc laterally than was previously appreciated. The parahippocanpal cortices by virtue of its cytoarchi tectonic, parahippocampal cortex is caudally adjacent to the pcrirhinal cor- chemoarchitectonic, and connectional characteristics. tex (Fig. 2A). Area TH is a thin strip of cortex caudal to the para- Our obsetvarions indicatc &at none of the existing termi- subiculum and cntorhinal cortex. Area 'TF is larger and is later- nologies for the cortical regions surrounding the posterior rhinal ally adjacent to TH. The region's lateral border is with the caudal sulcus in the rat accurately delimit the full extent of the perirhi- continuation of area TE, i.e., area TEO. rial cortex or capture the cytoarchitectonic, histochemical, and One obvious difference between the rat and monkey is that, connectional heterogeneity of this region (see Tablc 1 for a sum- in the rat, the perirhinal cortex occupies only caudal levels of the mary of existing terminologies). We wish to encourage the use of rhinal sulcus, whereas, in the monkey, the perirhinal cortex bor- the term perirhinal to encoinpass areas 35 and 36 in the monkey ders the full rostrocaudal extent of the rhinal sulcus (Fig. 2). and rostra1 areas 35 and 36 in the rat and the terms parahip- Otherwise, the spatial relationships among these regions are sim- pocampal to dcsignate areas TF and TH of the monkey brain and ilar for the two species. Entorhinal cortex, area 35, and area 36 postrhinal to designate a region that includes caudal areas 35 and lie adjacent to each other in the veiitrodorsd plane in the rat and 36 in the rat (Fig. 2). the mediolateral planc in the monkey. The postrhinal cortex in

TABLE 1.

Terminology for Cortical Regions Surrounding the Rkinal Sulcus'

Area 35 Area 36 Postrhinal

Reference -2.50 to -4.50 -4.50 to -7.80 -2.50 to -4.50 -4.50 to -7.80 (Ventral) (Dorsal)

Rose (1929) Perirkiizalis Pevivhinalis Ectorhinalis Ecforhiniilis Perivkinalis Ecfovkinalis Kreig (1946a,b) Caudal 13 Area 35 Caudal 14 20, Vent. 41 Area 35 Area 36 Deacon et al. (1983) Caudal AIp Perirhinal Caudal AIp Ectorhinal Postrhinal Ectorhinal Zilles and Wree (1985) Caudal ATp Perirhinal Caudal AIp Vent. Te3/2 Perirhinal Caudal Te2 Paxinos & Watson (1986) Perirhinal Perirhinal Perirh i nal Vent. 'l'e3/2 Perirhinal Caudal Te2 Swanson (1992) Perirhinal Perirhinal Ec torhinal Ectorh i na 1, Ectorhinal Ventral Te, Vent. Te,.

'Areas 35 and 36 are divided into anterior (-2.50 to -4.50 mm) and posterior (-4.50 to -7.80 mm) portions relative to bregnia PERIRHZNAL AND POSTRHINAL CORTICES OF THE RAT 393

R c Rat Brain, Lateral View

t v Monkey Brain, Ventral View C

FIGURE 2. A ventral surface view of the monkey brain adapted area 35 in the monkey, which is buried in the depths of the rhinal from Suzuki and Amaral (1994, A) and a lateral surface view of the sulcus, is not visible in this ventral view. Abbreviations: amts, an- rat brain (9) showing borders of the entorhinal, perirhinal, and terior middle temporal sulcus; ots, occipitotemporal sulcus; rs, rhi- parahippocampallpostrhinal cortices as described in this review. nal sulcus; STG, superior temporal gyms; areas TH, TF, and TE of Perirhinal cortex is shown in gray (area 36 in dark gray and area 35 von Bonin and Bailey (1947);Te3 and Te2, temporal cortex; Oc2L, in light gray), parahippocampalt’postrhinal cortices in mottled shad- secondary visual cortex. ing, and the entorhinal cortex (EC) in diagonal stripes. Note that

the rat and the parahippocampal cortex in the monkey are lo- fundus and along the dorsal bank of the rhinal sulcus for ap- cated caudal to the perirhinal and entorhinal cortices. proximately thc caudal half of the rhinal sulcus (Fig. 1E). The perirhinal and postrhinal cortices in the rat have clearly Swanson’s (1992) designation of the perirhinal and ectorhinal cor- proven difficult to demarcate based purely on cytoarchitectonic tices is much like that of Rose (Fig. IF). Swanson, however, sug- criteria. In fact, the two most widely cited historical resources for gested that the dorsal part of Kose’s ectorhinal cortex, where layer regional definitions of the cortex of the rat (Rose, 1929; Kreig, IV is more apparent, corresponds to temporal association cortex 1946a) differ substantially with regard to their placement of the in humans, and should thus be separated from agranular ec- boundaries of perirhinal cortex (Fig. 1A and B, respectively). torhinal cortex. ‘l‘his region was designated ventral temporal as- According to Rose, the perirhinal cortex is a long but narrow strip sociation cortex (Ted by Swanson (1992). of cortex extending along the posterior half of the rhinal sulcus. The regional delimitation of the perirhinal and ectorhinal cor- He also illustrated a fairly wide ectorhinal cortex that was situ- tex has varied largely because there is little agreement concerning ated just dorsal to the pcrirhinal arca. As is evident in Figure 1B, the definition of the borders of these regions with adjacent cor- Krieg’s (1946a) area 35 and 36 occupy only the caudal portion tical areas. In fact, the rostra1 border of the perirhinal cortex with of Rose’s perirhinal and ectorhinal regions. the insular cortcx varies by several niillimcters along the rostro- Modern workers continue to vary in their placernetit of the caudal axis from author to author. This is due, in part, to differ- boundaries of these cortical areas. Zilles et al. (1380), employing ing definitions of the insular cortex. As classically defined by Rose quantitative cytoarchitectonic techniques, defined perirhinal cor- (1928; Fig. 1A) in the human, monkey, and rodent, the insular tex as a transitional area lying in the fundus of the rhinal sulcus cortex overlies the claustrum. Thus, a number of neuroanatomists (Fig. 1D). This relativcly narrow rcgion was interposed between have adopted the caudal limit of the claustrum as a convenient entorhinal cortex, ventrally, and cortical area Te2, dorsally. landmark for the boundary between the insular and perirhinal Although Zilles did not illustrate a distinct area 36, his temporal cortices. Of the maps shown in Figure 1, those by Paxinos and regions Te2 and Te3 were said to include portions of areas 20; Watson, Zilles and Wree, and Swanson follow Rose’s lead in this 41, and 36 of Krieg (Zilles, Wree, 1985). Paxinos and Watson regard (see also Krettek, Price, 1977~;Cechetto and Saper, 1987). (1986) illustrate rhe perirhinal cortex as occupying a band of cor- Krieg (1346a; Fig. IB), in contrast, asserted that “regarding the tex broader than that of Zilles and Wree (1985) lying within the iiisula as coextensive with the cortex w-hich overlies the claustrum, 394 BURWELL ET AL. though a convenient criterion, is a specious one,” and he placed histochemical or immunohistochemical preparations that lend ad- the insular-perirhinal border more caudally than Rose. Ileacon et ditional confirmatory data concerning the proposed boundaries al. (I 983, Fig. 1C) adhered to Krieg’s suggestion (see also Miller and subdivisions of these regions. and Vogt, 1984; Turner and Zimmer, 1984). Regarding the ventral border of the perirhinal cortex and postrhinal cortex, there is The Monkey Perirhinal Cortex again some difference of opinion. Somr investigators show the entorhinal cortex as situated entirely ventral to the rhinal sulcus Area 35 of the macaque monkey perirhinal cortex is fairly ho- throughout its full rostrocaudal extent (Kreig, 1946a; Kosel, 1981; mogeneous cytoarchitectonically (Suzuki and Amaral, 19944. Deacon et al., 1983; Zilles and Wree, 1985; Paxinos, Watson, Layer I11 is poorly populated and forms a distinctive gap in cell 1986). Others, however, indicate that the caudal entorhinal cor- stains. Anothcr distinctivc fcature of this agranular cortcx is laycr tex not only occupies the fundus of the rhinal sulcus, but also en- V, which is populated by large, darkly stained, and densely packed compasses its dorsal bank (Swanson, 1992; Dolorfo and Amaral, cells that form an arc around the fundus of the rhinal sulcus (Fig. 1993). The dorsal borders of the pcrirhinal and postrhinal cor- 3A). In contrast to the homogeneity of area 35, area 36 shows tices are even more problematic. At one extreme, Zilles and Wree substantial rcgional variation in its cytoarchitcctonic appearance. (1 985) illustrate a very narrow perirhinal cortex bordered dorsally In general, it becomes more columnar and more differentiated as by areas Te3 and Te2. At the other extreme, Rose (1929) illus- one moves either laterally or caudally (Suzuki and Amaral, 19941). trates a very broad ectorhinal cortcx dorsal to perirhinal cortcx, One of the most distinctive feaiures of area 36 is layer IT, which which extends to primary auditory and visual areas. As noted is promincnt owing to the clusters of darkly stained spherical cells above, Swanson (1992) divides the ectorhinal region of Rose into that populate it. At rostral Ievels of area 36, these cell clusters ex- a ventral ectorhinal region and a dorsal “associational” cortex tend into layer I giving the layer 1/11 border an irregular appear- called ventral temporal association cortex. Again, the cytoarchi- ance. Unlike area 35, area 36 has a distinct layer IV, although it tectonic characteristics of this region in the rat brain provide in- tends to be very primitive in the medial portions of the area. sufficient criteria for easily, or at least consistently, setting boundaries between cortical areas. The posteromedial border of the The Monkey Parahippocampal Cortex postrhinal cortex is generally not addressed in descriptions of the Areas TH and TF of the parahippocampal cortex are clearly perirhinal and postrhinal cortex. Our own observations suggcst distinct from areas 35 and 36. Area TH, the morc primitive of that thc rctrosplenial region borders the postrhi nal cortex. the two areas, is agranular and bilaminate in appearance at ros- There is obviously little consensus about the boundaries of the tral level^, but is more laminar and contains a meager internal perirhinal and postrhinal cortices in the rat. Clearly, without con- granular layer at caudal levels. Area TF is more highly granular cise demarcation of the bordcrs and subdivisions of these regions with large, darkly stained cells in the infragranular layers. One of in the rat, it will be difficult to accuratcly asscss their contribu- the distinctive features of area 1’F is the very prominent layer V, tion to memoty. does one define cortical boundaries? How made up of large darkly stained pyramidal cells, that fuses with Classically, the definition of a cortical area was based almost ex- layer VI. clusively on cytoarchitectonic criteria. Modern nruroanatomical approaches, however, rely on both cytoarchitectonic and connec- The Rat Perirhinal Cortex tional data as well as on chemical neuroanatomical information concerning the region of interest. When all of these neu- Only very limited cytoarchitectonic descriptions of the rat roanatomical approaches are applied to the perirhinal and postrhi- perirhinal cortex are currently availablc in chc literature (Kreig, nal cortices, a much clearer picture of its organization is produced. 1946b; ’I’urner and Zimmer, 1984). The following is thus heav- In the following sections, we review the available cytoarchirec- ily based on our own observations. tonic, chemoarchitectonic, and connectional data of the perirhi- Area 35 in the rat is agranular cortex characterized by a broad nal and postrhinal cortices in the rat. layer 1 (Fig. 4B). This cortex can be distinguished from the nearby piriform and entorhinal cortices (Fig. 4A) by several features, e.g., the small round cells in layer 11. Layer 111 is poorly populated as in the monkey. Also similar to the monkey, layer V of area 35 is distinguished by the occurrence of large, darkly staincd pyramidal cells distributed throughout the layer. These darkly stained cells are organized in a gradient fashion with smaller cells located A casual survey of photomicrographs through the perirhi nal superficially and progressively larger cells located more deeply in cortex in the macaque monkey (Fig. 3A) and the rat (Fig. 3B) is the layer. sufficient to appreciate that these cortices are substantially wider Area 36 has a distinctly different cytoarchitecture from area and more distinctly laminated in rhe monkey. In this section, the 35. As in the monkey, area 36 is charactcrized by a prominent general cytoarchitectonic characteristics of the perirhinal and layer IT containing mostly round cells organized in distinctive parahippocampaUpostrhina1 corticcs in the monkey and rat are patches (Fig. 4C,L>).’l’he layer 11 cells are larger and often darker summarized and evaluated for areas of common features in the than those seen in area 35. A very weak granular laycr is prcsenc two species. For thc rat, data are also surveyed from a variety of in which granule cells are intermixed with the cells that consti- PERIRHINAL AND POSTRHINAL CORTICES OF THE RAT 395

FIGURE 3. Photomicrographs of Nissl-stained standard coronal sections through the perirhinal cortex of the macaque monkey (A) and the rat (B). Laminae are designated by Roman numerals. Area 35 for both species, area 36rm for the monkey, and the ventral portion of area 36 for the rat are shown. Scale bar = 500 pm.

tute layers I11 and V. In dorsal portions of area 36, layer IT re- a light band (Fig. jR). Although the Occurrence ofthrse two bands mains patchy, but is thinner than in ventral area 36 (Fig. 4D). clearly differentiates arca 36 from arca 35, the bands continue, Layer IV becomes more prominent in the dorsal portion of the albrit substantially more lightly, into the tlorsally adjacent cortex. field. 'l'hus, the 'l'inim's staining pattern provides only a partial indi- One useful histochemical preparation for defining cortical bor- cation of the dorsal border of area 36. ders is the Timrn's sulphide silver technique, which drmonstrates What do the cytoarchitectonic and othrr characteristics of the the distribution of heavy metals ('l'itnm, 1958; Haug, 1973; rat perirhinal cortex described above contribute to the definition Slovitor, 1982). Although cornprehensivc studies of these regions of borders with the surrounding cortical areas? Rostrally, thc in [he monkey using Timm's staining methods are not available pcrirhinal cortex abuts the postcrior insular cortex. Area 35 is eas- for comparison, this technique provides a useful marker for areas ily distinguishable from the pos[erior insular cortex on purely cy- 35 and 36 in the rat. Figure 5B shows a coronal Tirntn-stained toarchitectonic grounds. This most rostra1 portion of arca 35 is section of the rat brain that was cut in a plane oriented perpen- distinctly bilaminatc, whereas the postcrior insular cortex has an dicular to the rhinal sulcus. Area 35 is characterized by a single; isocortical or six-layered appearance. The differentiation of pos- densely mined band encompassing layers II through V (see also terior insulai cortcx from arca 36 is morc prohlematic. Pcrhaps Turner and Zimmer, 1984). Area 36 is distinguished from the the main features of the posterior insular cortex that differentiate homogeneously stairied area 35 by two dark bands separated by it from arca 36 arc the cell-sparsc gaps between laycrs 111 and V, 396 BURWELL ET AL. PERIRHINAL AND POSTRHINAL CORTICES OF THE RAT 397

tion will likely be made on the basis of connectional, rather than FIGURE 4. Photomicrographs of Nissl-stained standard coronal sections through the piriforni and entorhinal cortices (A), area 35 cytoarchitectonic, criteria. In the monkey, for example, area 36 (B), ventral area 36 (C), and dorsal area 36 (D) of the rat. Laminae can be differentiated from area TE (uniniodal visual association are designated by Roman numerals. Scale bar = 200 pm. cortex) because area 36 projects heavily to the entorhinal cortex and area TE does not. We would predict that a projection to the rat entorhinal cortex may also be a defining feature of the rat V and VI, and VI and the underlying claustrum (see also Krettek perirhinal cortex. arid Price, 1977~).The loss of thesc characteristic gap5 coincides rostrocaudally with the caudal limit of the claustrum and the level The Rat Postrhinal Cortex where we place the rostra1 border of area 36. The ventral border of the perirhiiial cortex is formed by the As noted above, Deacon et al.’s (1983) original definition of entorhinal cortex. In Nissl-stained marcrial, the border can bc dis- the postrhinal cortex has been expanded into a somewhat larger tinguished by several characteristics. For cxample, layer I I of the region. In the present report, the term posirhinal includes the cntorhinal cortex contains medium-to-large, darkly staincd stel- caudal levels of area 35 (as in Deacon et al.’s original usage) as late cells organizcd in clusters, whereas in area 35, layer I1 cells well as the caudal portion of area 36 (or ectorhinal cortex as in are smaller and lighter and are primarily round with a few pyra- Deacon et al.’s map). The ventral portion of postrhinal cortex is mids. The presence of the cell-sparse lamina dissecans in the en- agranular and bilaminate in appearance (Fig. 6A). A distinguish- torhitial cortex also distinguishes it from area 35. In Timm’s ma- ing feature is the presence of small ectopic layer I1 cells near the terial, the perirhinal cortex is heavily stained, whereas the border with the entorhinal cortex. The larger, dorsal portion of entorhinal cortex is much more lightly stained. Immunoreactivity the postrhinal cortex is more laminar and has a distinct layer I\’ for the calcium-binding protein parvalbuniin also denionstrates a (Fig. 6B). definite border (Fig. 5C, see also Dolorfo and Amaral, 1993). The postrhinal cortex can be differentiated from the rostrally Here, the entorhinal cortex is heavily labeled, whereas area 35 adjacent perirhinal cortex by the occurrence of the ectopic layer shows little or no labeling. Parvalbumin imniunoreactivity in su- I1 cells. ‘l’hese outpouchings of cells into layer I, give layer I1 a perficial Iayrrs also clearly distinguishes entorhinal cortex from distinctively irregular appearance in the ventral portion of the re- perirhinal cortex in the monkey (I’itkanen and Amaral, 1393). gion. The dorsal postrhinal cortex can be differentiated from ros- By most accounts, the dorsal border of the perirhinal cortex is tral levels of area 36 in that layer I1 is more densely packed and formed by association cortcx of some type, either niultirnodal as- thercfore not a.s patchy as in area 36. Finally, the deep layers of bociation cortex or auditory association cortex. There are bands the postrhinal cortex contain elongated cells chat are radially ori- of cortex lying dorsal to what is clearly area 36 that can be dis- ented, whereas layer VI of the perirhinal cortex contains elon- tinguished from it on [lie basis of cytoarchitectonic features. gated cells that are horizontally oriented. Whether these bands should be grouped within area 36 or within The postrhinal cortex is bordered medially by agranular ret- the dorsal association cortex is not presently clear. ’l‘his distinc- rosplenial cortex (Vogt, 1985). Agranular retrosplenial cortex, area

FIGURE 5. Photomicrographs of coronal sections of the rat marcated by arrows. In the Timm’s-stained material, area 36 is char- brain cut obliquely so that the plane of section is perpendicular to acterized by two darkly labeled bands that coalesce in area 35, but the rhinal sulcus. Adjacent sections are stained for Nissl (A), heavy the entorhinal cortex (EC) is lightly labeled. In contrast, the middle metals by the Timm’s method (B), and the calcium-binding protein layers of the entorhinal cortex stain heavily for parvalbumin, but the parvalbumin (Paw, C). The boundaries of areas 35 and 36 are de- perirhinal cortex is only lightly stained. Scale bar = 500p,m. FIGURE 6. Photomicrographs of Nissl-stained standard coronal sections through the ventral portion (A) and the dorsal portion (B) of the postrhinal cortex of the rat. Laminae are designated by Roman numerals. Scale bar = 200 pm.

FIGURE 7. Photomicrographs of sagittal sections stained for identified by two bands of staining in Timm’s material with a Nissl (A), heavy metals by the Timrn’s method (B), and AChE (C). broader, darker outer band. The entorhinal cortex (EC) is situated These images show the most caudodorsal aspect of the section where below Pas, and secondary visual cortex is located above POR. the parasubiculum (Pas) is identified by light staining for heavy Scale bar = 500wm. metal and dark staining for AChE. I’ostrhinal cortex (POR) is PERIRHZNAL AND POSTRHILNALCORTICES OF THE RAT 399

23d of Vogt and Peters (1 98 I), has a distinctly different cytoar- marily of round cells and deeper layers of larger, darkly stained chitectonic appcarance from postrhinal cortex. It has a broad fused cells. Nevertheless, the homology of postrhinal cortcx with layer II/III and a weak Iaycr IV made up of distinctive, larger cells. parahippocam pal cortex will rcly heavily on more detailed infor- Our observations indicate that the postrhinal cortex extends far- mation concerning the connectivity of these regions. ther posteromedially than indicated by previous descriptions of the perirhinal or ectorhinal cortices. In the caudomedial portion of the postrhinal cortex its ventral border is not with the entorhinal cortex. Rather, a thin band of the parasubiculum insin- uates between the entorhinal and postrhinal cortices. This can be apprcciated in sagittal sections stained for acerylcholinesrerase The Connections of the Monkey Perirhinal and (AChE) or by Timm’s method (Fig. 7). The parasubiculum stains intensely for AChE and forms a thin band just above entorhinal Parahippocampal Cortices cortex (Fig. 7C); in Timm’s-stained material this area is pile (Fig, Arguably, the most compelling feature of the connectivity of 7B). The postrliiiial cortex srains lightly for AChE, hut very perirhinal and parahippocanipal cortices in the monkey is the co ti- densely in the Tinim’s preparations. The region can be clearly nectivity with the hippocampal formation. In fact, Insausti et al. seen to form a narrow band above the parasubiculum. (1987) defined an enlarged area of the primate mediotemporal As with the perirhinal cortcx, the dorsal border of postrhinal lobe as belonging to thc perirhinal or parahippocampal cortices cortex is formed by association cortex of some type, but in this on the basis that cells throughout this region project directly to case it is either visual association cortex (Kreig, 1346b; Zilles et the entorhinal cortex. In the monkey, these cortical regions pro- al., 1380; Miller and Vogt, 1384; Zilles, Wree, 1985) or poly- vide almost two-thirds of the nzocortical input to the entorhinal modal association cortex (Swanson, 1332). In cell-stained mate- cortex (Insausti et al., 1987), which, in turn, provides the pre- rial, visual cortex is distinguished from the ventrally adjacent cor- dominant cortical input to the dentate gyms and hippocampus tex by a more prominent layer IV and a bilaminate layer \’I. In via the perforant pathway (Van Hoesen and Pandya, 1975~; Timm’s-stained material, visual association cortex demonstrates Witter et al., 1389b; Witter and Amaral, 1991). The topography clumps of dark precipitate associated primarily with layer I1 and of thc entorhinal interconnections with the pcrirhinal and the deep portion of layer I. Rased on the information available, parahippocam pal cortices has been described in detail by Suzuki it is not clcar whether postrhinal cortex abuts visual association and Amaral (1994b). The perirhinal cortex projects most heavily cortex or whether a band of polymodal association cortcx is in- to the rostrolateral two-thirds of entorbinal cortex, and the terposed. As with the perirhinal cortex, this distinction will likely parahippocampal cortex projects most heavily to the caudal avo- he made on thc basis of connectional criteria, and again, we pre- tli irds. dict that a projection to thc rat cntorhinal cortex will be a defin- The functional significance of the perirhinal and parahip- ing feature of the rat postrhinal cortex. A delimitation of the cor- pocampal projections to the entorhinal cortex of the hippocam- tical boundaries of the rat perirhinal and postrhinal cortices that pal formation is augmented by the information that these cor- reflccts all available neuroanatoniical information is illustrated in tices are themselves the focus of converging input from unimodal Figure 8. and polymodal associational cortices (Jones and Powell, 1970; Van Hoesen and Pandya, 1975a,b). Suzuki and Aniaral (1394a) Cross-Species Similarities and Differences provided evidencc that unimodal associational inputs arise from somatosensory, auditory, and visual association cortices. While In addition to the specific cross-species comparisons already the majority of the input to these cortices is from visual areas, noted, there are a number of similarities in the general organiza- different types of visual information reach the perirhinal and tional ftatures in the rat and monkey perirhinal and postrhi- parahippocampal cortices. Visual object information from area nal/parahippocanipal cortices. For example, there is a common TE predominantly reaches the perirhinal cortex, whereas visuo- gradient of incrcasing cytoarchitectonic differentiation along the spatial information is more lieavily directed to the parahip- rostrocaudal and ventrodorsal axcs (mediolateral in the monkey). pocampal cortex. Cortices identified with somatosensory proc- Area 36 becomes more radially orgnnized at caudal levels in both essing, primarily granular and agranular insular cortices, project species, and area 36 is thicker with more distinct cellular layers to both perirhinal and parahippocampal cortices. Auditory asso- than area 35. These same principles arc observed in thc postrhi- ciation cortex only projects to t Ire parahippocampal cortex. nal and parahippocampal cortices. Dorsal postrhinal cortex is The perirhinal and parahippocampal cortices receivc polysen- more highly laminated than ventral postrhinal cortex in the rat, sory information from ventrolateral and orbitofrontal cortices, and area TF is more highly laminated than area TH of thc cirigulaie and retrosplenial cortices, posterior parietal cortex, and parahipyocampal cortex in the monkey. the polymodal region of the dorsal bank of the superior tempo- Onc question of importance is whether postrhinal cortex in ral sulcus (Suzuki and Amaral, 1994a). All of thesc corticcs pro- the rat shares cytoarchitectonic characteristics with parahip- ject to par’ahippocampal cortex, but the predominant polymodal pocampal cortex in the nionkcy. The available data mggest that associational input to pcrirhinal cortex arises from [he parahip- thc ventral portion of the postrhinal cortex may sharc sonic fea- pocampal cortex and the superior temporal SIIIC~S.Interestingly, tures with area TH, ix., a combined layer 11/111 composed pri- while the parahippocampal cortex projects heavily to the perirhi- 400 BURWELL ET AL. PERIRHTNAL AND POSTRHINAL COATlCES OF THE RAT 401

FIGURE 8. A drawing of a three-quarter caudal view of the rat different regions of the perirhinal cortex are largely overlapping brain showing the borders of areas 35, 36, and the postrhinal cor- in the entorhirial cortrx, but there is a rough rostrocaudal topog- tex (top) and standard coronal sections showing the limits of the raphy. Kostral perirhinal cortex projects more strongly to rostral perirhinal and postrhinal cortices at four levels arranged from ros- and lateral regions of cntorhinal cortex, and caudal perirhinal cor- tral to caudal (A-D). Scale bar = 500 pm. tex preferentially projects more caudally in entorhinal cortex. Postrhinal cortex projects more heavily to the caudal entorhinal cortex than does the caudal perirhinal cortex. Projections from nal cortex, the perirhinal cortex projection to the parahippocam- the postrhinal cortex innervate both lateral and medial regions of pal cortex is rather meager. Thus, the monkey perirhinal and the entorhinal cortex, although the labeling in lateral regions is parahippocanpal cortices appear to be the primary intermediaries heavier. between the neocortex and the hippocampal formation. Although there havc been reports that the entorhinal cortex In addition to their connectivity with the neocortex and the gives rise to a return projection to the perirhinal and postrhinal hippocampal formation, the perirhinal and parahippocampal cor- cortices (Deacon et al., 1983; Kohler, 19881, the topography and tices are also interconnected with the amygdala, the basal ganglia, laminar pattern of these projections have not been extensively ex- and the thalamus. The perirhinal and parahippocampal cortices amined. Our findings indicatc that the rostral entorhinal cortex project to the lateral, basal, and accessory basal nuclei of the amyg- projects preferentially to the perirhinal cortex, whereas the cau- daloid complex (Van Hoesen, 1981; Stcfinacci et al., 1994). The dal entorhinal cortex projects both to perirhinal and postrhinal amygdaloid projections arise more from the perirhinal cortex than cortices. Preliminaiy data suggest that layers 111 through V of ros- from the parahippocampal cortex. The return projections origi- tral entorhinal cortex near the rhinal sulcus give rise to the pro- nate primarily from the same nuclei. jections to the perirhinal cortex, although the labeling is heavier Available information indicates that rhe perirhinal and para- from the deep layers. Layer V of the caudal regions of the en- hippocampal cortices provide substantial input to portions of the torhiiial cortex projects to the perirhinal and postrhinal cortices. striatun, including the caudate nucleus, putamen, and nucleus ac- The available literature suggests that widespread neocortical ar- cuinbens (Yeterian and Van Hoesen, 1978). The temporal polar eas project extensively to the perirhinal and postrhinal cortices. portion of perirhiiial cortex projects to ventrotnedial portions of Table 2 presents a compilation of references for neocortical in- the caudate nucleus and the putamen (Van Hoesen et al., 1981). puts to perirhinal cortex. Owing to the pronounced difference.~ There is some evidence that the remaining regions of the perirhi- in how the perirhinal borders are defined in these studies and the nal cortex project sparsely to ventral regions of the head and often incidental manner with which projections to the perirhinal prominently to lateral portions of the tail of the caudate nucleus cortex arc presented, the data summarized in this table should be (Saint-Cyr et al., 1990). The perirhinal cortex also projects to the considered tentative and in need of confirmation. Miller and Vogt nucleus accumbens (Hemphill et al., 1981). The parahippocam- (1984) reported that area 35 receives input from primary visual pal cortex projects more prominently to the head of the caudate area 17 (which was also reported to project to sensory, motor, nucleus than does perirhinal cortex, but with a patchy terminal and association cortices!) as well as from visual association area distribution (Saint-Cyr et al., 1930). The parahippocampal cor- 18a (see also Deacon et al., 1983; Vaudano et al., 1990; Paperna tex also projects heavily to the tail of the caudate nucleus, espe- and Malach, 1991). Area 36 was also reported to receive input cially to dorsal portions (Van Hoesen et al., 1981). from areas I8a and I811 Primary auditory cortex does not pro- There is limited information available about the interconnec- ject to perirhinal coi-tex, but a thin strip of auditory association tivity of the thalamus with the perirhinal and parahippocampal cortex, located ventrally and caudally to thc primary region, does cortices in the monkey (reviewed in Witter et al., 1989a). The project to rostral perirhinal cortex (Vaudano et al., 1990; perirhinal cortex clearly projects to the medial division ofthe pul- Komanski and I,eDoux, 1993; Mascagni er al., 1993). Regarding vinar (Yeterian and Pandpa, 1988), and there is also evidence that somatosensory input, Deacon et al. (1983) reported input from the perirhinal cortex projects at least lightly to the mediodorsal rostral, ventral, and posterior regions of insular cortex to area 35 thalamus (Aggleton et al., 1986; Russchen et al., 1987). The (see also Saper, 1982: Guldin arid Markowitsch, 1983). Olfactory parahippocampal cortex projects to the medial pulvinar, the me- input to the pcrirhiiial cortex arises from the periamygdaloid re- dial dorsal nucleus, and the lateral dorsal nucleus (Ualeydier and gion (Krettek and Price, 1977a; Deacon et al., 1983) and piri- Mauguiere, 1985; Russchen et al., 1987; Yeterian and Pandya, form cortex (Guldin and Markowitsch, 1983; Luskin and Price, 1988). 1983). Our preliniinary retrograde tracing findings confirm that the perirhinal cortex receives substantial input from somatoseii- The Connections of the Rat Perirhinal and sory and auditory associational cortices and olfictory areas. The Postrhinal Cortices postrhinal cortex, in contrast, receives strong input from visual association cortex, weak input from somatosensory association While there has thus far been no comprehensive analysis of cortex, and little or no input from auditory and olfactory regions. the perirhinal projection to the entorhinal cortex in the rat, our The polymodal associational cortices that provide input to own findings indicate that the perirhinal and postrhinal cortices perirhinal cortex include the medial prefrontal (Reckstead, 1979; give rise to robust projections to the entorhinal cortex, which are Deacon et al., 1983; Guldin and Markowitsch, 1983; Cornwall stronger to lateral regions than to medial regions. Projections from and Philiipson, 1988; Sesack et al., 1989; Reep et al., 1990; TABLE 2.

Cortical Input to Peerirhinal Cortex

Frontal regions Frontal area 2 Deacon et ill. (1983); Reep, et al. (1990); Guldin and Markowitsch (1983) Anterior cingulate Deacon et al. (1987); Beckstead (1979); Takagishi and Chiha (19Y1); Conde et al. (1995) I’relimb ic Deacon et al. (1983); Sesack et al. (1989): Beckstead (1979); Hurley et al. (1991); Conde et al. (1995) Infralimbic Hurley et al. (1991); Conde et al. (1995) Lateral orbital Deacon et al. (1983) Retrosplenial cortex Deacon el al. (1983); Arnault and Roger (1990); Wyss and Van Groen (1992) Olfactory cortex Piriform Luskin and Price (1983); Guldin and Markowitsch (1983) I’eriamygdaloid Deacon et ill. (lY83); Luskin and Price (1983); Krettek and Price, 1977a-c Insular cortex Deacon et al. (1983); Guldin and Markowitsch (1983); Saper (1982) Parietal cortex Deacon et al. (1983); Guldin and Markowitsch (1983) Temporal cortex TElv, TE2 Romanski and LeDoux (1993); Mascagni et al. (1993); Papcrna and Millnch (1991); Vaudano et al. (1990) TE3 Deacon et al. (1953); liomanski and LeUoux (1993); Mascagni et al. (1993) Occipital cortex Deacon et al. (1983); Miller and Vogt (1984); Paperna and Malach (1991); Vaudano et al. (1990)

Hurley ct al., 1991; Conde et a]., 19951, ventrolateral prefrontal receive input from the lateral nucleus, hut the area 35 projection (Deacon et al., 1c)83), and anterior cingulate (Beckstead, 1979; is somewhat more substantial. Area 36 is reciprocally connected Deacon et al., 1983; Takagishi and Chiba, 1991; Conde et al.? with the magnocellular division of the basal nucleus and area 35 1995) cortices (Table 2). Projections from ventral temporal cor- with the paniicellular division of the basal nucleus. There is a mi- tices also are well documented (Deacon et al., 1983; Mascagni er nor reciprocal connection with the accessory basal nucleus. al., 1993; Romancki and LeDoux, 1993).These cortices are likely There ib little published information on the connections of che to be polyniodal associational regions rather than auditory :wo- pcrirhinal and postrhirial cortices with the striatum. Our studies ciation cortices (Mascagni et al., 1993). Our observations also in- indicate that the perirhinal cortex projects substantially to the dicate that the perirhinal cortex receives polymodal input from striatum, particularly to medial regions of the body and tail of the postrhinal cortex. While the retrosplenial cortex is reported the caudate nucleus (see also McGeorge and Faull, 1989; Vaudano to project to the perirhinal cortex (Deacon et al., 1983; Arnault et al., 1990). Area 35 projects moderately to the nucleus accum- and Roger, 1990; Wyss and van Croen, 1992), there is no pub- hens and to the tail of the caudate nucleus. Area 36 exhibits strong lished information on the strength or topography of this projcc- projcctions to the nucleus accumhens, the most medial portion tion. Our preliminary data provide evidence that the anterior cin- of the body, and tail of the caudate nucleus. The postrhinal cor- gulate, retrosplenial, and posterior parietal cortices project tex projects heavily only to the most caudal and dorsal margin of strongly to the postrhinal cortex but not to the perirhinal cortex. the body and the tail of the caudate nucleus. The primary subcortical connections of the perirhinal cortex We examined the patterns ofthe perirhinal and postrhinal pro- include strong projections to the arnygdala, the striatum and the jections to the thalamus and found regional differences (Burwell thalamus. The postrhinal cortex also projects to the striaturn and et al., 1994). For the perirhinal cortex, the projection from area the thalamus but has few or no connections with the aniygdaloid 36 is more robust than chat from area 35. While all portions of complex. Postrhinal cortex, hut not perirhinal cortex, is inter- the pcrirhinal cortex project to midline thalamic nuclei (see also connected with che claustrum (Burwell and Amaral, unpublished Herkenham, 1978; Cornwall and Phillipson, 1 988j, subregions findings). of areas 35 and 36 can be distinguished by thc pattern of cffer- Several amygdaloid nuclei are interconnected with thc rat ciit connectivity with other thalamic regions. For example, ros- perirhinal cortex. Our own findings indicate that the perirhinal tral hut not caudal area 36 projects to posterior nuclei (see also cortex is intcrconnccted with the lateral, bad, and accrssory basal Dracon et al., 1983). Only the 1-ostralportion of area 35 projects nuclei of the amygdala (see also Krettek and Price, 1974, 1977b; to the mediodorsal thalamic nucleus. Our own preliminary stud- Ottersen, 1382; McDonald and Jackson, 1987; Vaudano et al., ies indicate that the perirhinal and postrhinal cortices are also dis- 1990; Roinanski and LeDoux, 1993) as well as the capsular re- tinguished hy their thalamic projections. Unlike the perirhinal gion of the central nucleus. The heaviest projections terminate in cortex, the postrhinal cortex projects to the anterior and lateral the lateral nucleus and the capsule of the central nucleus and arise nuclear groups. The perirhinal and postrhinal cortices are further from all portions of perirhinal cortex. Area 36 projects more distinguished by their thalamic input. While both rcgions receive 5rrongly to these nuclei than does area 35. Both are;1s 36 and 35 input from midline thalamic nuclci, the projections are heavier PERIRHINAL AND POSTRHINAL CORTICES OF THE RAT 403 to perirhinal than to postrhinal cortex. Oiily the pcrirhinal cor- nal corticrs in the rat suggests that two broad principles of corti- tex rcceivcs input from the auditory thalamus, and only the cal connectivity are exhibited in both species. First, as in the rnon- postrhinal cortex receives input from the lateral posterior thala- key, the rat perirhinal and postrhinal cortices give rise to strong mus. 00th regions reccive input from the perigeniculate region, projeccions to thc hippocampal formation via the entorhinal cor- but from different portions. A surnn~aryof the cortical and sub- [cx. Moreover, the projections exhibit similar topographies in the cortical connections reviewed here is presented in Figure 9. two species. The second principle common to both the rat and [he monkey is that unimodal and polymodal association areas pro- Cross-Species Similarities and Differences ject extensively to the perirhinal and postrhiriallparahippocanlpal cortices. In both species these regions receive extensive unimodal A review of the conncctivity of the pcrirhinal and parahip- associational input; however, the topography and relative contri- pocarnpal cortices in the monkey and the perirhinal and posrrhi- butions of this input differ. In the monkey, the perirhinal and

Cortical Connect ions

Medial prefrontal cortex Orbital prefrontal ctx Anterior cingulate ctx Insular cortex Retrosplenial cortex Occipital cortex Auditory association ctx Parietal cortex Perirhinal cortex Piriform cortex Somatosensory ctx Periamygdaloid area Entorhinal cortex Postrh i nal cortex \ n

Amydaloid complex Caudate nucleus Claustrum Nucleus accumbens Midline thalamic Lateral posterior Perigeniculate region nuclei thalamic nucfeus of the thalamus Subcortical Connections

FIGURE 9. Summary diagram of the cortical and subcortical connections of the perirhinal and postrhinal cortices. ctx, cortex. parahippocampal cortices rcceive a preponderance of visual in- TABLE 3. puts, with the parahippocampal cortex also receiving a small com- plement of auditory and somatosensory associational input. For Surface Areu of Senso y Covtical Regions the rat, the magnitude and distribution of sensory information YO of Neocortex appears to he more evenly weighted in the perirhinal and postrhi- Sensory nal cortices. The perirhinal cortex receives primarily soniatoseri- Cortical Areas' Monkey Rat sory, auditory, and olfactory input, and the postrhinal cortcx receives primarily visual and some somatosensory input. In both Total visual areas2 48.2 17.9 spccics, these regions receive polymodal associational input-, but Occipital 34.0 11.9 the parahippocampal cortcx in the monkey and the postrhinal Parietal 4.8 3.5 cortex in the rat receive the most widespread and extensive input. Temporal 8.4 2.5 Morcoever, the parahippocampal cortex in the monkey and the Auditory areas 3.4 4.0 postrhinal cortex in the rat provide a major source of polymodal Somatosensory areas3 11.5 25.9 associational input to the perirhinal cortex. Olfactory areas4 1.2 14.4 In addition to the shared attributes already described, the re- 'Surface areas for the monkey are taken from Felleman and Van Essen gions surrounding the rhinal sulcus in both spccics also project (1991); however, we exclude some areas known to be polyinodal from importantly to several suhcortical structures. While available data the list of visual areas (ie., areas STP, TF/TH, 7a, and 46). Surface ar- are so limited as to make direct comparisons between the rat and eas for the rat are taken from Swanson (1Y92). monkey difficult, the rat and monkcy pcrirhinal and postrhi- >For the rat we include posterior parietal cortex (Swanson, 1992) and rialiparahippocampal cortices appear to make connections with the visual portions of area 36 (Miller and Vogt, 1984). the same subcortical structures and even the same subnuclei of 3Somatosensory areas for the rat include the barrel fields which account these structures. for over one-quarter of the total area. Qlfactory areas (piriform and peridmygdaloid cortices) constitute an area equivalent tct the indicated percentages of neocortex.

ses similar to those used in monkcys to explore t-hese brain regions (e.g., Miller and Desimone, 1994).

The monkey perirhinal and parahippocampal corticcs preferentially receive visual input, whereas the rat perirhinal and postrhinal cortices receive unimodal sensory input that is more cvenly weighted across sensory modalities. It niiglic be useful to consider species differences in unimodal sensory input to these Unfoldcd maps of the regions surrounding the rhinal sulcus regions within the framework of the relative amounts of the cor- for the monkey (Fig. 1OA) and the rat (Fig. 10B) reveal that tlic tical surface areas dedicated to the various sensory modalities in combined area of the perirhinal and parahippocampal cortices in the two species (Table 3). While almost half of the monkey neo- the monkey is about four times the area of the entorhinal cortex, cortex is involved in unimodal visual processing (Felleman and whereas in the rat, the perirhinal and postrhinal cortices are about Van Essen, 1991), only one-sixth of the rat neocortex is visual the same size as the entorhinal cortex. Jn contrast, the perirhi- (cxtracted from Swanson, 1992). The relative cortical area dedi- nal/parahippocampaI cortices in the monkey and the perirhi- cated to processing auditory stimuli is about the same in the two naUpostrhina1 cortices in the rat account for roughly similar per- species, but the somatosensory regions are relatively larger in the centages of the entire neocorrical surfice area, about 5% (data rat. Thus, if the monkey pcrirhinal and parahippocampal cortices from (Felleman and Van Essen, 1991, for the monkey and retlect the types of sensory processing that are carried out by the Swarison, 1992, for the rat). Why would the entorhinal cortex be remainder of the neocortex, it follows that these cortices would relatively smaller in the monkey? One possible explanation is that, be overwhelmingly visual. Because the amounts of cortical area as proposed above, the area of the perirhinal and parahippocam- dedicated to visual, auditory, and somatosensory processing are palipostrhinal cortices simply scales linearly with the total surface more equivalent in the rat, it also follows that these sensory sys- area of the remainder of the neocortex. The size of the entorhi- tems should have a more evenly distributed input to the perirhinal cortex, however, may not scalc with the ncocortex, but with nal and postrhinal cortices. The differences in unimodal input to the size of the olfactory system. Remember, the perirhinal and the perirhinal parahippocampalipostrhinal cortices in the mon- parahippocampslipostrhinal cortices in the monkey and rat actu- key and the rat should not imply that they play different roles in ally receive little direct olfactory input. In contrast, the entorhi- memory function. Rather, these cortices may carry out the same nal cortex receives a direct input from the olfactory bulb. In the memory-related computations albeit on different types of sensory rat virtually all of the surface area of the entorhinal cortex receives information. A search for the fundamental operation of these te- a direct olfactory input. Although carlicr studies reportcd that gions awaits sophisticated hehavioral/clcctrophysiological analy- only the lateral entorhinal cortex received olfactory input PERIRHINAL AND POSTRHINAL CORTICES OF THE RAT 405 A B

Monkey Rat

R TF/TH - Scale Bar 2 mm for the Monkey M 1 mm for the Rat tt-.9 C

FIGURE 10. Representative unfolded two-dimensionalmaps of the monkey (A, adapted from Suzuki, hard, 1994a) and the rat (B, Burwell and Amaral, unpublished findings) entorhinal, perirhinal and parahippocampaUpostrhinalcortices. Layer IV was unfolded in the monkey and either layer IV or a line between layers I11 and V unfolded in the rat. These unfolded maps can be related to the surface views in Figure 8 and in Figure 2 where the same shading patterns are used to indicate areas of interest.

(Heimer, 1968; Price and Powell, 1971), later studies confirmed transition from cortex that gives rise to prominent projections to that these projections extend to the medial entorhinal cortex the entorhinal cortex to that which gives rise ro little or no pro- (Heimer, 1978; Kosel et al., 1981). In the monkey, only about jections to the entorhinal cortex. Unfortunately, there is no cur- 12% of the entorhinal cortex receives a direct olfactory input rently published data to answer this question for the rat, and thus (Amaral et al., 1987). Thus, the entorhinal cortex may be rela- a comprehensive analysis of the inputs to the entorhinal cortex tively larger in the rat because of its greater contribution to ol- using retrograde tracing techniques is needed. factory information processing. The Issue of Parahippocampal Cortex Defining the Borders We ha\re suggested that the postrhinal cortex in the rat may In the rat, the rostral, ventral, and posteromedial borders of be homologous to the parahippocarnpnl cortex in the monkey. the perirhinal cortex are clearly identified by a variety of coiinec- This suggestion is based primarily on topological, histochemical, tional, histochemical, and immunohistochemical data. The dor- and connectional criteria (for discussions of homology and com- sal border of the perirhinal and postrhinal cortices, however, can- parative neuroanatomy, see Campbell and Hodos, 1970; Rosene not be resolved conclusively based on existing cytoarchitectonic and Van Hoesen, 1987). Because a resolution of the question of and cheinoarchitectonic data. One of the defining characteristics homology between these structures is important for studies at- of the perirhinal and parahippocampal cortices in the moiikcy is tempting to use rodent and primate models for the analysis of the projection to the entorhinal cortex (Suzuki and Amaral, human memory, it will be critical to generate the connectional 1994a). If the monkey situation is taken as a guide, it follows that information most useful in making this determination. Some con- the dorsal border of these regions may also be indicated as the nectional characteristics of the parahippocampal cortex in the 406 BURWFLL ET AL. monkey that might be useful in establishing homology include absence of cntorhinal damage. More studies exploring the effects the origins of the polyrnodal associational input, the pattern of of complete, selective lesions of the perirhinal and postrhinal cor- connectivity with the perirhinal cortex, and the patterns of down- tices on memory tasks are needed to determine the role of these stream connections including those with the entorhinal cortex and cortices in recognition and other forms of memory. subcortical structures. Even with the relatively meager connec- Investigators have made an important beginning in under- tional data that are available, it appears that a preliminary case standing the function of the cortical regions surrounding the rhi- can be made for homology between the monkey and rat perirhinal sulcus in the rat and in developing appropriate rat models of nal areas on the one hand, and the parahippocampal cortex in the human memory, but many questions remain. What is the fun- monkey and the postrhinal cortex in the rat on the other. To give damental operation performed on the sensoiy information re- a few examples, the monkey parahippocampal cortex receives in- ceived by the perirhinal and postrhinal cortices? Do these regions put from more multimodal associational areas than does the contribute preferentially to only certain forms of memory? Other perirhinal cortex; it receives a prominent input from the retro- than memory, to what cognitive processes might they contribute? splenial cortex, whereas the perirhinal cortex does not. As iridi- How does the fitictinn of the postrhinal cortex differ from that cated earlier, the postrhinal cortex of the rat receives a retrosple- of the perirhinal cortex? We have summarized the available neu- nial input but the perirhinal cortex does not. The monkey roanatomical information about the perirhinal and postrhinal cor- parahippocampal cortex projects heavily to the perirhinal cortex tices in the rat and highlighted some of the remaining issues to but not vice versa. Again the same appears to be true for the be resolved in the hopes of providing a firmer ground for re- postrhinal and perirhinal cortex in the rat. Finally, the monlicy searchers addressing these questions and others in the endeavor paraliippocarnpal cortex is less strongly connected with the amyg- to identify the functional role of the cortical regions surrounding dala than the perirhinal cox-tex, and the same relationship holds the posterior rhinal sulcus in the Iat. for the rat postrhinal and perirhinal cortices. Clearly, more connectional information about these regions in the rat will help to Acknowledgments establish the validity of this neutoanatomical homology and will This research was supported in part by NIH grant (NSI 6980) lead to a better framework For the analysis of the functional ho- to D.G.A., an NIMH postdoctoral fellowship (NSO9247) to mology of these regions. R.D.B., NATO grant (0758/88) to M.P.W. and D.(;.A.,and the Human Frontier Scicnce Eoundation. The authors grarefully appreciate comments by Drs. Howard Eichcnbaum, Peter Kapp, and Wendy Suzuki who read earlier versions of this manuscript. We also acknowledge the contributions of Cynthia Dolorfo, Jaye Niederniair, and Janet K'eber. The evidence that the perirhinal and parahippocampal cortices contribute importantly tu normal memory processing in the nion- key has fostered an increasingly intense interest in the comparable regions of the rat brain. Behavioral studies in the rat have been hampered, however, by the lack of comprehensive neuroanatomical information. At this time only a few experirnentnl lesion stud- Aggleton JP, Desirrione R, Mishltin M (1986) The origin, course, and ies of the rat perirhinal cortex have been attempted. Some have termination of the hippocamporha~amicprojections in the Macaque. addressed the contribution of the perirhinal cortex to spatial learn- J Comp Neurol 243:409-42 1. 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