Abstract

The projections from the amygdaloid complex to the hippocampus and surrounding cortex have a critical role in the formation of memories for emotionally arousing stimuli and in the spread of epileptic seizures. The present study investigated the organization of amygdaloid projections to the perirhinal and postrhinal cortices by injecting the anterograde tracer Phaseolus vulgaris leucoagglutinin into the different subdivisions of the lateral, basal or accessory basal nuclei of the amygdala in rat (n = 53). Analysis of immunohistochemically stained sections indicated that the medial and dorsolateral divisions of the lateral nucleus project heavily to layers I–V of caudal area 35 and to layers I–III of the rostroventral postrhinal cortex. The dorsolateral division also moderately innervates layer I of caudoventral area 36. The magnocellular division of the basal nucleus projects moderately to layers V and VI of rostral areas 35 and 36. The parvicellular division of the accessory basal nucleus projects moderately to layer V of caudal area 35, whereas the magnocellular division projects moderately to layers I and II of rostral area 35. Via these substantial, topographically organized projections, the amygdaloid complex might modulate information processing at different levels of the medial temporal lobe memory system.

AB accessory basal nucleus, ABmc accessory basal nucleus, magnocellular division, ABpc accessory basal nucleus, parvicellular division, AE entorhinal cortex, amygdaloentorhinal subfield, AHAl amygdalohippocampal area, lateral division, AHAm amygdalohippocampal area, medial division, area 35 area 35 of the perirhinal cortex, area 36 area 36 of the perirhinal cortex, BAOT bed nucleus of the accessory olfactory tract, Bi basal nucleus, intermediate division, Bmc basal nucleus, magnocellular division, Bpc basal nucleus, parvicellular division, c central nucleus, capsular division, CA1 CA1 field of the hippocampus, CA3 CA3 field of the hippocampus, CE entorhinal cortex, caudal entorhinal subfield, CEi central nucleus, intermediate division, CEl central nucleus, lateral division, COa anterior cortical nucleus, COp posterior cortical nucleus, DIE entorhinal cortex, dorsal intermediate entorhinal subfield, DLE entorhinal cortex, dorsal lateral entorhinal subfield, I intercalated nucleus, Ldl lateral nucleus, dorsolateral division, Lm lateral nucleus, medial division, Lvl lateral nucleus, ventrolateral division, m central nucleus, medial division, Mc medial nucleus, caudal division, Mcd medial nucleus, dorsal portion of the central division, Mcv medial nucleus, ventral portion of the central division, ME entorhinal cortex, medial entorhinal subfield, Mr medial nucleus, rostral division, PAC periamygdaloid cortex, PACm periamygdaloid cortex, medial division, paraSUB parasubiculum, POR postrhinal cortex, SUB subiculum, TF area TF of the parahippocampal cortex, TH area TH of the parahippocampal cortex, VIE entorhinal cortex, ventral intermediate entorhinal subfield

Introduction

The amygdaloid complex is composed of >10 nuclei and cortical areas, each of which have unique cytoarchitectonic, chemoarchitectonic and connectional characteristics (Price et al., 1987; Amaral et al., 1992; Pitkänen et al., 1997,2000). According to recent lesional (Roozendaal and McGaugh, 1997), behavioral (Hamann et al., 1999), pharmacological (Packard et al., 1994; Packard and Teather, 1998), and electrophysiological (Ikegaya et al., 1994,1995,1996) studies, one of the major functions of the amygdala in rats, nonhuman primates and humans is the enhancement of memory formation for emotionally arousing events (Cahill and McGaugh, 1998; McGaugh, 2000). Pathways from the amygdala to the medial temporal lobe memory system [which includes the dentate gyrus, hippocampus proper, entorhinal cortex, perirhinal cortex and parahippocampal cortex — equivalent to the postrhinal cortex in the rat (Squire and Zola-Morgan, 1991)] form one component of the circuitries assumed to be involved in this task (McGaugh, 2000). Another condition in which the amygdalo-hippocampal projections are presumed to have a critical role is the spread of seizure activity from the amygdala to the hippocampus and surrounding cortex in temporal lobe epilepsy (Gloor, 1992). Relatively little is known, however, about the details of topographic organization of these pathways. Such information might be of value for understanding the cellular mechanisms underlying memory formation and epileptogenesis in the medial temporal lobe.

Previous tract-tracing studies indicate that the lateral, basal and accessory basal nuclei of the amygdala innervate primarily the temporal end of the hippocampus, either monosynaptically or via the entorhinal cortex (Krettek and Price, 1977a; Pikkarainen et al., 1999). The perirhinal and postrhinal cortices, in turn, project preferentially to the entorhinal subfields (Burwell et al., 1995; Naber et al., 1997; Burwell and Amaral, 1998), which innervate the septal hippocampus and the subiculum in the rat (Ruth et al.1982,1988; Witter et al.1989; Dolorfo and Amaral, 1998). In addition, the perirhinal cortex innervates the septal subiculum/CA1 region monosynaptically (Deacon et al.1983; Kosel et al.1983; Romanski and LeDoux, 1993; McIntyre et al.1996; Naber et al.1999; Shi and Cassell, 1999). In the rat, the perirhinal and postrhinal cortices are heavily interconnected with each other as well as with the entorhinal cortex (Burwell et al.1995; Naber et al.1997; Burwell and Amaral, 1998). Therefore, monosynaptic projections from the amygdaloid complex to the perirhinal and postrhinal cortices provide a pathway via which the amygdala could modulate the neuronal activity in the septal hippocampus polysynaptically. Such projections also provide a route via which the amygdala could innervate these two cortical components of the medial temporal lobe memory system monosynaptically in parallel.

Projections from the amygdala to the perirhinal cortex in the rat have been investigated in previous tract-tracing studies (Krettek and Price, 1977a,b; Deacon et al.1983; McDonald and Jackson, 1987; Arnault and Roger, 1990; Petrovich et al.1996). In most of these reports, however, tracer injections were not limited to one subdivision of the amygdala (anterograde tracers) or a specific region of the perirhinal cortex (retrograde tracers), and therefore many of the details of these connections are lacking. Further, to our knowledge, the projections from the amygdala to the rat postrhinal cortex have not been investigated in detail. Here, we investigated the distribution and topography of projections from the amygdala to the perirhinal and postrhinal cortices in rat by placing small injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) into different divisions of the lateral, basal and accessory basal nuclei of the amygdala. The data indicate that these projections are abundant and highly topographically organized.

Materials and Methods

Anterograde Tract-tracing with Phaseolus vulgaris Leucoagglutinin (PHA-L)

Male Wistar rats (National Laboratory Animal Center, Kuopio, Finland) weighing 275–350 g were used. The experiments were approved by the provincial government of Kuopio, Finland. All animal procedures were conducted in accordance with the guidelines of the European Community Council directives 86/609/EEC.

Rats were anesthetized i.p. (4 ml/kg) with a mixture of sodium pentobarbital (9.7 mg/ml), chloral hydrate (10 mg/ml), magnesium sulfate (21.2 mg/ml), propylene glycol (40%) and ethanol (10%). The anterograde tracer PHA-L (2.5% in 0.1 M sodium phosphate buffer, pH 7.4; #L-1100, Vector, Burlingame, CA) was injected iontophoretically (positive-pulsed 4 μA current, 7 s on and 7 s off for 8–10 min) into the lateral nucleus (n = 20) (Pikkarainen et al.1999), basal nucleus (n = 16) (Savander et al.1995) or accessory basal nucleus (n = 17) (Savander et al.1996; Pikkarainen et al.1999) of the left amygdala. A detailed description of the surgical and injection procedures as well as of the processing and storing of the sections has been described previously (Pitkänen et al.1995; Pikkarainen et al.1999).

To identify PHA-L-immunoreactive fibers, a one-in-five series of sections was processed according to the immunohistochemical staining method described previously (Gerfen and Sawchenko, 1984). The primary antibody used was rabbit anti-PHA-L (dilution 1:8,000; #B275, DAKO, Glostrup, Denmark or #AD1818, Chemicon, Temecula, CA), and the PHA-L was visualized by incubating the sections in a solution containing 0.05% diaminobenzidine (#34001, Pierce, Rockford, IL) and 0.04% hydrogen peroxide in 0.02 M KPBS (pH 7.4). For a detailed description of the immunohistochemical staining procedure, see Savander et al. (Savander et al.1995). An adjacent series of sections was stained with thionin to identify the borders of the various amygdaloid nuclei and regions of the perirhinal and postrhinal cortices.

Analysis of Sections

The sections were analyzed microscopically under brightfield and darkfield illumination. PHA-L-filled cell bodies in the injection site were plotted with a computer-aided digitizing system (Minnesota Datametrics, St Paul, MN) from every fifth section (one-in-five series, 30 μm thick). An adjacent thionin-stained section was superimposed on top of the computer-generated plot under a stereomicroscope equipped with a drawing tube, and the outlines of the amygdaloid nuclei were drawn on each plot using a camera lucida.

PHA-L-labeled fibers were considered to constitute a terminal plexus if they were thin and branching, and had varicosities (e.g. the terminal plexus in layers I–V of area 35 in Fig. 4C). If the labeled fibers were thick and straight, with few or no varicosities, they were considered to be passing fibers (e.g. fibers passing through layer VI of area 35 in Fig. 4C,D). The density of PHA-L-labeled terminals was determined based on visual assessment and assigned to one of four density grades of terminal labeling: very light or passing fibers (e.g. the sparse straight fibers in layer VI of area 36 in Fig. 4B, which appear nonvaricose under a higher magnification), light (e.g. the individual criss-crossing fibers in layer I of area 36 in Fig. 4C, which have a large number of varicosities under a higher magnification), moderate (e.g. the plexus of terminals on dark background in layer III of area 35 in Fig. 4C) or heavy (e.g. the dense plexus of fibers in the deep portion of layer I of area 35 in Fig. 4C, which entirely covers the background).

Two-dimensional unfolded maps of the perirhinal and postrhinal cortices were constructed according to the method described by Van Essen and Maunsell (Van Essen and Maunsell, 1980). For a detailed description of the construction of unfolded maps, see Pikkarainen et al. (Pikkarainen et al.1999). Unfolding of the cortices was done along layer II, and the fundus of the rhinal fissure was used as a reference point. The density of PHA-L-labeled terminals (light, moderate or heavy) was determined as described above.

Brightfield photomicrographs were taken with a Nikon Multiphot 6 × 9 cm system (Nikon, Tokyo, Japan). Darkfield photomicrographs were taken with a Nikon Microphot-FXA camera system (Nikon, Tokyo, Japan). The outlines of cytoarchitectonic boundaries and layers of the perirhinal and postrhinal cortices were drawn from thionin-stained sections with the aid of a stereomicroscope equipped with a drawing tube. Thereafter, the darkfield photomicrographs were scanned using a UMAX scanner linked to a Power Macintosh computer and the background and dust spots were removed by painting with Adobe Photoshop 4.0 software. Finally, the scanned outlines were redrawn using Canvas 3.5 software and superimposed on the scanned photomicrographs.

Results

Nomenclature

The Amygdaloid Complex

In the present study, we used a slight modification of the nomenclature of Price and co-workers (Price et al.1987) for the rat amygdaloid complex [for modifications, see Pitkänen et al. (Pitkänen et al.1997,2000)]. The deep nuclei of the amygdala consist of the lateral nucleus (dorsolateral, ventrolateral and medial divisions), the basal nucleus (magnocellular, intermediate and parvicellular divisions) and the accessory basal nucleus (magnocellular and parvicellular divisions) (Fig. 1).

The Perirhinal and Postrhinal Cortex

The cytoarchitectonic borders of the perirhinal and postrhinal cortices were defined according to Burwell and co-workers (Burwell et al.1995; Burwell and Amaral, 1998). Briefly, the perirhinal cortex is bordered rostrally by the insular cortex and caudally by the postrhinal cortex. The perirhinal cortex can be partitioned into areas 35 and 36 (Fig. 2). Area 35 is narrower, and occupies the ventral bank and the fundus of the rhinal sulcus. Area 36 is dorsal to area 35 and occupies the dorsal bank of the rhinal sulcus. The postrhinal cortex is caudal to the perirhinal cortex and dorsal to the rhinal sulcus (Fig. 2).

To avoid confusion in the data interpretation, it is important to note that, according to Burwell and co-workers (Burwell et al.1995), the rostral border of the perirhinal cortex with the insular cortex is located at –2.8 mm from bregma (Paxinos and Watson, 1986). In most of the previous studies investigating the interconnectivity between the amygdala and the perirhinal cortex, the rostral border of the perirhinal cortex has been placed more caudally; that is, at the level of approximately –3.5 to –4.0 from bregma (Ottersen, 1982; McDonald and Jackson, 1987; Shi and Cassell, 1999). As the present analysis shows, there is a dramatic change in the density of the projections from the amygdala to the perirhinal cortex at the level of approximately –4.0 from bregma. Therefore, to aid in the description and the comparison of data with previous studies, we show the density of projections to the rostral (i.e. –2.8 to –4.0 from bregma) and caudal (i.e. –4.0 to –7.8 from bregma) perirhinal cortex separately in Tables 1–3 and in unfolded maps (Fig. 3).

Location of PHA-L Injection Sites

We analyzed 53 PHA-L injections and a large majority of the tracer-filled cells were localized within one subdivision of the lateral (n =20), basal (n = 16) or accessory basal (n = 17) nucleus (Fig. 1, Tables 1–3) (Savander et al.1995,1996; Pikkarainen et al., 1999). Typically, the injection site extended through 3–5 sections (section thickness 30 μm, one-in-five series). The distribution and density of terminal labeling in the perirhinal and postrhinal cortices was more dependent on the location of the injection within the amygdala rather than on the number of labeled neurons at the injection site. In occasional cases, we found a few PHA-L-positive cells in the surrounding amygdaloid nuclei or cortical areas (e.g. periamygdaloid cortex or piriform cortex), or along the injection tract within the striatum. When the appearance of terminal labeling in the perirhinal and postrhinal cortices was compared with that in ‘pure’ amygdaloid injections, we concluded that such contamination of injection sites provided only a minor contribution, if any, to the projection pattern. Next, the projection patterns in the perirhinal and postrhinal cortices from each deep amygdaloid nucleus or nuclear subdivision are described.

Projections to the Perirhinal Cortex: Area 35

Lateral Nucleus

The dorsolateral and medial divisions of the lateral nucleus originated the heaviest projections from the amygdala to area 35 (Figs 3–5, Table 1). The dorsolateral division heavily innervated almost the entire rostrocaudal extent of area 35, whereas the projection from the medial division was limited mostly to its caudal aspect. That is, caudal to the level of –4.0 from bregma (Paxinos and Watson, 1986) the density of terminal labeling increased rapidly from very light to moderate-to-heavy (e.g. Fig. 5C,D). Typically, labeled terminals covered the entire dorsoventral extent of the area. Analysis of the laminar distribution of labeling indicated that the projection from the dorsolateral division terminated most heavily in the deep portion of layer I, in layer II and in the superficial portion of layer III (Fig. 4, Table 1). The medial division, in turn, innervated most heavily layers I–V (Fig. 5D,E, Table 1).

The location of the injection site within the dorsolateral and medial divisions also affected the density of the projections. First, the projection from the caudal aspect of the dorsolateral division was slightly heavier than that from the rostral portion. Further, this projection was evenly distributed throughout superficial layers I–III, whereas the projection from the rostral aspect of the dorsolateral division most heavily innervated layer I (Fig. 4, Table 1). Secondly, the rostral portion of the medial division projected heavily to the caudal two-thirds whereas the caudal portion projected to the caudal half of area 35 (Figs 3 and 5). Finally, projections from the dorsocaudal portion of the medial division to area 35 were heavier than those from the ventrocaudal portion (Table 1).

Projections from the ventrolateral division were substantially lighter than those from the dorsolateral and medial divisions (Fig. 3, Table 1) and they terminated primarily in the deep portion of the layer I, layers II and III, and layer V of caudal area 35 (Table 1).

Basal Nucleus

The magnocellular division of the basal nucleus provided substantial projections to the rostral one-third of area 35 (Figs 3 and 6B,C). Within this region, the projection was heavier rostrally than caudally and extended throughout the entire dorsoventral extent of area 35. The highest density of terminal labeling was located in layers V and VI, whereas layers II and III contained only light labeling (Fig. 6B–D, Table 2). The projection to area 35 formed a continuum with the projection terminating in the rostrally located insular cortex.

The intermediate and parvicellular divisions originated only light projections to area 35 (Fig. 3, Table 1). The intermediate division projected to layer V of the rostral portion of area 35. The lateral portion of the parvicellular division of the basal nucleus innervated mainly layers II and V of the ventral aspect of caudal area 35. The projection from the caudomedial parvicellular division, in turn, innervated primarily layer V of the entire dorsoventral extent of area 35.

Accessory Basal Nucleus

The accessory basal nucleus gave origin to substantial projections to area 35, which were, however, less prominent than those from the lateral nucleus (Figs 3 and 7, Table 3). The projections from the parvicellular division were moderate in density and terminated throughout the dorsoventral extent of layer V of caudal area 35 (Figs 3 and 7, Table 3). Rostrally, the labeling was lighter and innervated only the ventral aspect of area 35 (Fig. 3).

Projections from the magnocellular division were light-tomoderate in density and terminated in layers I and II of the rostral one-third of area 35 (Fig. 3, Table 3). Typically, terminal labeling extended throughout the dorsoventral extent of area 35 (Fig. 3).

Projections to the Perirhinal Cortex: Area 36

Lateral Nucleus

The projection from the lateral nucleus to area 36 was substantially lighter than that to area 35 (Figs 3–5, Table 1). The dorsolateral division innervated mainly the caudal two-thirds of ventral area 36 (Figs 3 and 4). Projections terminated in layer I, whereas layers II–VI contained only a few terminals intermingled with passing fibers. In the more dorsal aspect of area 36, the light projection terminated almost exclusively in layer I (Fig. 4B–D).

The ventrolateral and medial divisions projected lightly to area 36 (Figs 3 and 5, Table 1). The ventrolateral division mainly innervated layer V of the ventral extreme of area 36 (Fig. 3). The medial division, particularly its rostral portion, projected to layers I–VI of the caudal two-thirds of the most ventral extreme of area 36 (Figs 3 and 5, Table 1). Only the projection to layers I and V reached the more dorsal aspect of area 36 (Fig. 5C,D).

Basal Nucleus

The projection from the magnocellular division to area 36 was even heavier than that to area 35 (Figs 3 and 6, Table 2). The projection terminated mainly in layers V and VI of the rostral portion of area 36 (Figs 3 and 6B,C, Table 2). As in area 35, the projection to area 36 extended throughout its dorsoventral extent (Figs 3 and 6).

Projections from the intermediate and parvicellular divisions to area 36 were less prominent than projections from the magnocellular division (Fig. 3, Table 2). The intermediate division projected lightly to layers V and VI, whereas the parvicellular division provided a light projection to layer V of the rostral portion of area 36.

Accessory Basal Nucleus

The magnocellular division originated a light-to-moderate projection mainly to layers I–III of the rostroventral aspect of the area 36 (Fig. 3, Table 3). The parvicellular division, in turn, provided a light projection to layers I–V of the most ventral aspect of area 36 (Figs 3 and 7, Table 3).

Projections to the Postrhinal Cortex

Lateral Nucleus

The dorsolateral and medial divisions provided heavy topographically organized projections to the postrhinal cortex (Figs 3, 4F,G and 5F,G, Table 1). The highest density of terminal labeling was observed in layers I–III of the rostroventral aspect of the postrhinal cortex. The dorsoventral and laminar distribution of labeled fibers depended, however, on the location of the injection in the dorsolateral and medial divisions. First, the rostral dorsolateral division projected mainly to layer I of the ventral postrhinal cortex (Fig. 3). The caudal portion projected to layers I–III of the ventral, as well as to layer I of the more dorsal aspect of the postrhinal cortex (Fig. 4F,G). Secondly, the rostral portion of the medial division projected lightly to layers I–V of the more dorsal aspect of the postrhinal cortex (Fig. 5F).

The ventrolateral division originated the weakest projection from the lateral nucleus to the postrhinal cortex (Fig. 3, Table 1). Light terminal labeling innervated layers I–V of the rostral two-thirds of the most ventral postrhinal cortex.

Basal Nucleus

The basal nucleus did not project to the postrhinal cortex. In some cases, there were occasional straight nonvaricose fibers that resembled fibers en passage in the deep layers of the ventral aspect of the postrhinal cortex (Table 2).

Accessory Basal Nucleus

The accessory basal nucleus also provided substantial input to the postrhinal cortex, even though the projections were lighter than those from the lateral nucleus (Figs 3 and 7, Table 3). Typically, the accessory basal nucleus innervated layers I–III of the rostroventral aspect of the postrhinal cortex. Projections arising in the parvicellular division were light-to-moderate in density (Fig. 7), whereas the magnocellular division originated only light projections.

Contralateral Projections

There were no contralateral projections from the lateral and basal nuclei to the perirhinal or postrhinal cortices. Injections into the accessory basal nucleus occasionally gave rise to some light labeling in contralateral area 35 (in 7/17 cases). In some of the cases, labeling was observed mainly in layer I, whereas the other cases contained labeling in layers I–VI.

Course of Fibers from the Deep Amygdaloid Nuclei to the Perirhinal and Postrhinal Cortices

Projections originating in the lateral nucleus traveled first through the nucleus, then the external capsule and thereafter the angular bundle, before arriving in the deep layers of the perirhinal and postrhinal cortices.

PHA-L-filled fibers from the magnocellular and intermediate divisions of the basal nucleus traveled through the lateral portion of the parvicellular division. After leaving the basal nucleus, these fibers, as well as the fibers from the parvicellular division of the basal nucleus, traversed the external capsule and entered the perirhinal and postrhinal cortices through their deep layers. Some of these fibers appeared to travel first through the lateral nucleus before entering the external capsule.

Tracer-filled fibers from the accessory basal nucleus traveled first through the parvicellular and intermediate divisions of the basal nucleus, then joined at the external capsule and/or the angular bundle to enter the deep layers of the perirhinal and postrhinal cortices. Some labeled fibers seemed to traverse the external capsule, the endopiriform nucleus, and the deep layers of the piriform and entorhinal cortices before entering the perirhinal cortex.

Discussion

The present study was designed to determine the major principles of the organization of projections from the lateral, basal and accessory basal nuclei of the amygdala to the perirhinal and postrhinal cortices in the rat. To accomplish this, small injections of the anterograde tracer PHA-L were placed into different divisions of the lateral, basal or accessory basal nuclei of the amygdala, and the laminar organization of projections in the different regions of the perirhinal and postrhinal cortices was analyzed. The major principles of the organization of these projections are (see also Figs 8 and 9): (i) selective subnuclei of the lateral (dorsolateral and medial divisions), basal (magnocellular) and accessory basal (parvicellular) nuclei give origin to prominent topographically organized projections to the perirhinal and postrhinal cortices; (ii) typically, one nucleus or even one nuclear division innervates different parts of the perirhinal or postrhinal cortex in parallel; (iii) the heaviest projections terminate in caudal area 35 and the rostroventral postrhinal cortex; (iv) unlike the amygdalo-hippocampal projections (Pikkarainen et al.1999), some of the projections from the lateral and accessory basal nuclei to the perirhinal and postrhinal cortices terminate in an overlapping manner. These projections are, however, segregated from the main projections originating in the basal nucleus; (v) via projections to the perirhinal and postrhinal cortices, the amygdala might influence the septal and mid-septotemporal levels of the hippocampus; and (vi) comparison of the data of the present study and our previous one (Pikkarainen et al.1999) indicates that the basal nucleus is the major source of projections to the hippocampus proper, whereas the lateral nucleus heavily innervates the entorhinal, perirhinal and postrhinal cortices. The accessory basal nucleus appears to provide substantial inputs to all of these regions.

Comparisons of the Present Findings with Previous Studies in the Rat

Several previous studies report projections from the lateral (Krettek and Price, 1977a,b; Ottersen, 1982; Deacon et al.1983; McDonald and Jackson, 1987; Arnault and Roger, 1990), basal (Krettek and Price, 1977b; McDonald and Jackson, 1987) or accessory basal (McDonald and Jackson, 1987; Petrovich et al.1996) nuclei of the amygdala to the perirhinal cortex in rat. Little, however, is known regarding the projections from the amygdala to the postrhinal cortex (Krettek and Price, 1977a; Deacon et al.1983).

Consistent with previous observations, the heaviest amygdaloid projections to the perirhinal cortex originate in the lateral nucleus (McDonald and Jackson, 1987). Topographic analysis of these projections indicates that they terminate in layers I–V throughout the dorsoventral extent of area 35, whereas projections to area 36 are relatively meager and terminate only in its narrow ventral-most aspect. Like the lateral nucleus, the accessory basal nucleus innervates mainly area 35, area 36 being only lightly innervated. The density of this projection, however, is lighter than that from the lateral nucleus but heavier than that from the basal nucleus. Previously, Krettek and Price (Krettek and Price, 1977b) suggested that the projections from the basal nucleus to the perirhinal cortex terminate mainly in layers I and VI. Our data reveal that the main projections from the basal nucleus terminate in layer V of rostral area 35 and in layers V and VI of rostral area 36, and that there are only occasional PHA-L-labeled fibers in the superficial layers. Finally, the present findings indicate that the lateral and accessory basal nuclei provide substantial projections to layers I–III of the rostroventral postrhinal cortex.

The most important new finding of the present study is that the distribution and density of projections are highly dependent on the subdivisional location of the PHA-L injection within the amygdaloid nuclei. For example, the medial division of the lateral nucleus projects heavily to layers I–V of caudal area 35 and to layers I–III of the rostroventral postrhinal cortex, whereas the dorsolateral division also innervates area 35 more rostrally as well as layer I of ventral area 36. Projections from the ventrolateral division of the lateral nucleus to the perirhinal and postrhinal cortices are meager. Within the basal nucleus, the most substantial projections originate in the magnocellular division and terminate in the rostral aspects of areas 35 and 36. The caudomedial portion of the parvicellular division provides light projections to the caudal two-thirds of the perirhinal cortex. Finally, within the accessory basal nucleus, most of the projections originate in the parvicellular division and terminate in layer V of caudal area 35. Lighter projections from the magnocellular division terminate in layers I–III of area 35 as well as in layers I–III of the adjacent rostroventral area 36.

Organization of Projections from the Amygdala to the Perirhinal and Postrhinal Cortices

The analysis of projections from the lateral, basal and accessory basal nuclei to the perirhinal and postrhinal cortices reveals four major principles in the organization of these pathways. First, only selective nuclei or nuclear divisions give rise to these projections. For example, the most prominent projections originate in the medial and dorsolateral divisions of the lateral nucleus, in the magnocellular division of the basal nucleus and in the parvicellular division of the accessory basal nucleus. These observations suggest that, like the projections from the amygdala to the other functional systems (e.g. from the central nucleus to the brain stem autonomic centers), the projections to the medial temporal cortex have selective output regions in the amygdaloid complex.

Secondly, many of the nuclei or nuclear divisions provide substantial parallel inputs to more than one area within the perirhinal and postrhinal cortices. For example, the medial division of the lateral nucleus substantially innervates both caudal area 35 and caudoventral area 36 as well as the rostroventral postrhinal cortex. The magnocellular division of the basal nucleus innervates both rostral area 35 as well as rostral area 36. Perhaps the most point-to-point organized projections originate in the magnocellular and parvicellular divisions of the accessory basal nucleus, which terminate in rostral area 35 and caudal area 35, respectively. It remains to be studied whether the parallel projections from the lateral and basal nuclei to the different cortical areas originate in the same or different neurons.

Both areas 35 and 36, as well as the rostroventral postrhinal cortex, receive substantial inputs from the amygdala. There are, however, clear rostrocaudal, dorsoventral and laminar topographies in the organization of these projections. For example, the rostral perirhinal cortex is innervated only by the magnocellular division of the basal nucleus and the magnocellular division of the accessory basal nucleus. The caudal aspects of the perirhinal cortex receive inputs from the medial and dorsolateral divisions of the lateral nucleus as well as from the parvicellular division of the accessory basal nucleus. The dorsoventral topography is the most distinct in caudal area 36 and the postrhinal cortex. The dorsal aspects of these regions do not receive any substantial inputs from the amygdala whereas their ventral aspects are heavily innervated by the dorsoventral and medial divisions of the lateral nucleus. Analysis of the laminar topography indicates that in area 35, particularly caudally, many of the projections terminate throughout layers I–VI. In caudal area 36 and in the postrhinal cortex, however, the distribution of terminal labeling is limited to the superficial layers.

Some regions of the perirhinal and postrhinal cortices converge information from more than one nucleus or nuclear subdivision. For example, layer V of caudal area 35 receives substantial inputs from the medial division of the lateral nucleus as well as the parvicellular division of the accessory basal nucleus. Another example is layers I and II of the postrhinal cortex, which converge information from the dorsolateral and medial divisions of the lateral nucleus. In general, however, the perirhinal cortex converges information from all deep nuclei, whereas the postrhinal cortex is innervated by only the lateral nucleus.

Functional Aspects

The present and our previous study (Pikkarainen et al.1999) indicate that the deep amygdaloid nuclei provide substantial parallel inputs to different components of the parahippocampal– hippocampal network [for a definition of the parahippocampal and hippocampal areas, see Scharfman et al. (Scharfman et al.2000)]. For example, the lateral nucleus heavily innervates the parahippocampal region, including the perirhinal, postrhinal and entorhinal cortices, and the parasubiculum. The basal nucleus is the major source of projections from the amygdala to the hippocampus. These pathways innervate the temporal end of the CA3 and the CA1 subfields, and the temporal subiculum. The accessory basal nucleus, in turn, provides substantial inputs both to the parahippocampal areas, including the perirhinal and entorhinal cortices and the parasubiculum, and to the hippocampus, including the CA1 subfield. The functional significance of the parallel innervation of the different levels of the parahippocampal–hippocampal system by the amygdala remains to be studied.

Area 35, ventral area 36 and the rostroventral postrhinal cortex receive the heaviest inputs from the amygdala. These cortical regions project heavily to the lateral entorhinal cortex (Burwell et al.1995; Naber et al.1997; Burwell and Amaral, 1998), which in turn projects to the septal and midseptotemporal levels of the hippocampus (Ruth et al.1982,1988; Witter et al.1989; Dolorfo and Amaral, 1998). Because the monosynaptic inputs from the amygdala to the hippocampus are directed to its temporal aspect (Krettek and Price, 1977a; Pikkarainen et al.1999), projections from the amygdala to the perirhinal and postrhinal cortices provide a route via which the amygdala can also modulate the more septal aspects of the hippocampus.

Some of the interconnections between the amygdala and the perirhinal and postrhinal cortices appear to be reciprocal (Ottersen, 1982; McDonald and Jackson, 1987; Romanski and LeDoux, 1993; Shi and Cassell, 1999). A retrograde study by Shi and Cassell (Shi and Cassell, 1999) demonstrated that the lateral nucleus receives substantial inputs from layers II–VI of the dorsal bank of the perirhinal cortex (corresponding area 36) and the fundus of the rhinal sulcus (corresponding area 35), as well as from the superficial layers of the postrhinal cortex [levels –7.6 and –8.0 in figs 18 and 19 of Shi and Cassell (Shi and Cassell, 1999)]. We have demonstrated, however, that these regions are innervated by the lateral nucleus, even though the projection from the lateral nucleus does not extend as dorsally in area 36 as the projection from this region to the lateral nucleus. The accessory basal nucleus is also reciprocally connected with areas 35 and 36, even though the overall density of projections is lighter than that of the lateral nucleus (Shi and Cassell, 1999). Projections from the perirhinal cortex to the basal nucleus are, however, substantially heavier than the projections from the basal nucleus to the perirhinal cortex, as we (present study) and others (Shi and Cassell, 1999) have shown.

How similar is the organization of projections from the amygdala to the perirhinal and postrhinal cortices in rat compared with that in nonhuman primates? If we accept the recently proposed view that the perirhinal cortex (areas 35 and 36) and the postrhinal cortex in rat (Burwell et al.1995) correspond to the perirhinal cortex (areas 35 and 36) and the parahippocampal cortex (areas TH and TF) in the monkey [see the discussion in Burwell (Burwell, 2000)], respectively, there are both similarities and differences in the organization of projections from the amygdala to these regions. First, as in the rat, the monkey lateral and accessory basal nuclei also provide substantial projections to the perirhinal cortex. In the monkey, however, the intermediate and parvicellular divisions of the basal nucleus also project to the perirhinal cortex (Stefanacci et al.1996). Further, in rats these projections terminate mainly in area 35 and in a narrow ventral-most strip of the dorsally adjacent area 36. In contrast, in monkeys, the amygdala appears to innervate mainly area 36 (Stefanacci et al.1996). Secondly, analysis of retrograde-tracer injections indicates that the major source of projections from the amygdala to the parahippocampal cortex in the monkey is the magnocellular (and intermediate) division of the basal nucleus (Stefanacci et al.1996). In the rat, the postrhinal cortex is innervated mainly by the lateral and accessory basal nuclei.

Recent studies indicate that one of the major functions of the amygdala is to enhance memory formation for emotionally arousing events in rats, nonhuman primates and humans (Ikegaya et al., 1994, 1995, 1996; Packard et al.1994; Roozendaal and McGaugh, 1997; Cahill and McGaugh, 1998; Packard and Teather, 1998; ,Hamann et al.1999; McGaugh, 2000). The topographically organized projections from the amygdala to the hippocampal formation and parahippocampal area [see also Pikkarainen et al. (Pikkarainen et al., 1999)] provide candidate pathways in which such functions can be processed. Another function in which the amygdaloid projections to the perirhinal and postrhinal cortices might have an important role is the spread of seizure activity from the amygdala to the hippocampus and surrounding cortex (Gloor, 1992).

Taken together, the present data indicate that the lateral, basal and accessory basal nuclei of the rat amygdala provide substantial topographically organized projections to the perirhinal and postrhinal cortices. These connections provide candidate pathways via which the amygdala can modulate memory formation for emotionally arousing stimuli as well as spread seizure activity from the amygdala to the parahippocampal regions in temporal lobe epilepsy.

Table 1

The distribution of PHA-L-labeled fibers and terminals in the penihinal and postrhinal cortices after PHA-L injections in the dorsolateral (Ldl), ventrolateral (Lvl) and medial (Lm) division of the lateral nucleus of the rat amygdala1

1 Density of projections: •••=heavy; •• = moderate; • = light, and ○ = very light or passing fibers; Abbreviations: AP-level = antero-posterior level; Caudal areas 35 and 36 (i.e., -40 --7:8 from the bregma); L = lateral; M = medial; mid = middle; Rostral areas 35 and 36 (i.e., -2.8 --4.0 from the bregma).

Table 2

The distribution of PHA-L-labeled fibers and terminals in the penihinal and postrhinal cortices after PHA-L-injections in the mognocellular (Bmc) intermediate (Bi) and parvicellular (Bpc) division of the basal bucleus of the rat amygdala1

1 Density of projections: ••• = heavy; •• = moderate; • = light, and ○ = very few fibers or passing fibers; Abbreviations: AP-level = antero-posterior level; Caudal areas 35 and 36 (i.e., -4.0--7.8 from the bregma); L = lateral; M = medial; mid = middle; Rostral areas 35 and 36 (i.e., -2.8 --4.0 from the bregma).

Table 3

The distribution of PHA-L-labeled fibers and terminals in the penihinal and postrhinal cortices after PHA-L injections in the magnocellular (Bmc), intermediate (Bi) and parvicellular (Bpc) division of the basal nucleus of the rat amygdala1

1 Density of projections: ••• = heavy; •• = moderate; • = light, and ○ = very few fibers or passing fibers; Abbreviations: AP-level = antero-posterior level; Caudal areas 35 and 36 (i.e., -4.0--7.8 from the bregma); L = lateral; M = medial.; Rostral areas 35 and 36 (i.e., -2.8--4.0 from the bregma).

Figure 1.

 (A–F) Line drawings of coronal sections through the rat amygdala arranged from rostral (A) to caudal (F), demonstrating the location of the PHA-L injection sites in the lateral, basal and accessory basal nuclei. Each injection is shown with a different shading pattern. Rostral–caudal levels in relation to bregma are indicated for each section in the lower left corner (Paxinos and Watson, 1986) Scale bar = 500 μm. (G) A brightfield photomicrograph illustrating the PHA-L injection site in case R93-96 (located in the rostral portion of the medial division of the lateral nucleus). (H) A brightfield photomicrograph of an adjacent thionin-stained section demonstrating the boundaries of the medial division of the lateral nucleus. Scale bar = 250 μm in panels G and H.

Figure 1.

 (A–F) Line drawings of coronal sections through the rat amygdala arranged from rostral (A) to caudal (F), demonstrating the location of the PHA-L injection sites in the lateral, basal and accessory basal nuclei. Each injection is shown with a different shading pattern. Rostral–caudal levels in relation to bregma are indicated for each section in the lower left corner (Paxinos and Watson, 1986) Scale bar = 500 μm. (G) A brightfield photomicrograph illustrating the PHA-L injection site in case R93-96 (located in the rostral portion of the medial division of the lateral nucleus). (H) A brightfield photomicrograph of an adjacent thionin-stained section demonstrating the boundaries of the medial division of the lateral nucleus. Scale bar = 250 μm in panels G and H.

Figure 2.

 (A) Line drawings of coronal sections through the rat perirhinal and postrhinal cortices arranged from rostral (s1) to caudal (s6), indicating the borders of areas 35 and 36 of the perirhinal cortex and the postrhinal cortex (case R95-96). Scale bar = 1 mm. (B–G) Brightfield photomicrographs of thionin-stained coronal sections (s1–s6) demonstrating the cytoarchitectonics of the areas of the perirhinal and postrhinal cortices shown in panel A. The arrowheads demarcate anatomic boundaries of areas 35 and 36 and the postrhinal cortex, and Roman numerals (I–VI) refer to the layers. Scale bar = 250 μm in panels B–G.

Figure 2.

 (A) Line drawings of coronal sections through the rat perirhinal and postrhinal cortices arranged from rostral (s1) to caudal (s6), indicating the borders of areas 35 and 36 of the perirhinal cortex and the postrhinal cortex (case R95-96). Scale bar = 1 mm. (B–G) Brightfield photomicrographs of thionin-stained coronal sections (s1–s6) demonstrating the cytoarchitectonics of the areas of the perirhinal and postrhinal cortices shown in panel A. The arrowheads demarcate anatomic boundaries of areas 35 and 36 and the postrhinal cortex, and Roman numerals (I–VI) refer to the layers. Scale bar = 250 μm in panels B–G.

Figure 3.

 Two-dimensional unfolded maps summarizing the distribution of terminal labeling in areas 35 and 36 of the perirhinal cortex and in the postrhinal cortex after PHA-L injections into the lateral, basal or accessory basal nuclei of the rat amygdala (case number is shown in parentheses). Projections from each division of the lateral, basal and accessory basal nuclei are presented in a separate unfolded map. In the unfolded maps, the intensity of gray shading corresponds to the density of terminal labeling (the density gradations are shown in the lower right corner). The small arrows in the lower right corner indicate the orientation of the cortical surface. The dashed line marks the fundus of the rhinal fissure (rf). The vertical line marked with –4.16* illustrates the rostrocaudal level at –4.16 from bregma (Paxinos and Watson, 1986). The distribution of PHA-L-labeled terminals in different layers of areas 35 and 36 (areas rostral to level –4.16 are referred to as 35* and 36*) and the postrhinal cortex are presented in a box under each unfolded map. Note that the heaviest and most widespread projections to the perirhinal and postrhinal cortices originate in the dorsolateral and medial divisions of the lateral nucleus. Note also that in many cases the density of projections in the perirhinal cortex changes near the level of –4.16 from bregma.

Figure 3.

 Two-dimensional unfolded maps summarizing the distribution of terminal labeling in areas 35 and 36 of the perirhinal cortex and in the postrhinal cortex after PHA-L injections into the lateral, basal or accessory basal nuclei of the rat amygdala (case number is shown in parentheses). Projections from each division of the lateral, basal and accessory basal nuclei are presented in a separate unfolded map. In the unfolded maps, the intensity of gray shading corresponds to the density of terminal labeling (the density gradations are shown in the lower right corner). The small arrows in the lower right corner indicate the orientation of the cortical surface. The dashed line marks the fundus of the rhinal fissure (rf). The vertical line marked with –4.16* illustrates the rostrocaudal level at –4.16 from bregma (Paxinos and Watson, 1986). The distribution of PHA-L-labeled terminals in different layers of areas 35 and 36 (areas rostral to level –4.16 are referred to as 35* and 36*) and the postrhinal cortex are presented in a box under each unfolded map. Note that the heaviest and most widespread projections to the perirhinal and postrhinal cortices originate in the dorsolateral and medial divisions of the lateral nucleus. Note also that in many cases the density of projections in the perirhinal cortex changes near the level of –4.16 from bregma.

Figure 8.

 A line drawing summarizing the distribution of projections from the lateral, basal and accessory basal nuclei of the rat amygdala to the perirhinal and postrhinal cortices. The color code within the box on the right indicates the projection origin and its density. Coronal sections are arranged from rostral (on the left) to caudal (on the right). Arrowheads delineate the anatomic boundaries of areas 35 and 36, and the postrhinal cortex. Dashed lines delineate and Roman numerals (I–VI) refer to layers of the perirhinal and postrhinal cortices. The rostrocaudal levels (s1–s6) of the panels in relation to bregma are the same as in Figure 2. Note that the projections converge mainly in the superficial layers of area 35 of the perirhinal cortex and in the superficial layers of the rostroventral postrhinal cortex. Scale bar = 500 μm.

 A line drawing summarizing the distribution of projections from the lateral, basal and accessory basal nuclei of the rat amygdala to the perirhinal and postrhinal cortices. The color code within the box on the right indicates the projection origin and its density. Coronal sections are arranged from rostral (on the left) to caudal (on the right). Arrowheads delineate the anatomic boundaries of areas 35 and 36, and the postrhinal cortex. Dashed lines delineate and Roman numerals (I–VI) refer to layers of the perirhinal and postrhinal cortices. The rostrocaudal levels (s1–s6) of the panels in relation to bregma are the same as in Figure 2. Note that the projections converge mainly in the superficial layers of area 35 of the perirhinal cortex and in the superficial layers of the rostroventral postrhinal cortex. Scale bar = 500 μm.

Figure 9.

 A schematic line drawing summarizing the interconnections between the lateral, basal, or accessory basal nuclei of the amygdala with the hippocampal and parahippocampal areas. (1) The deep amygdaloid nuclei or their subdivisions receive information from various components of the hippocampal and parahippocampal areas [for review see Pitkänen et al. (Pitkänen et al., 2000)]. (2) Intra-amygdaloid circuitries (arrows indicate the main projections) distribute the incoming signals via parallel and serial routes to one or more amygdaloid region (adapted from Pitkänen et al., 1997). (3) The lateral, basal and accessory basal nuclei provide substantial projections to the perirhinal and postrhinal cortices, particularly to area 35, ventral area 36 and the ventral postrhinal cortex, which are summarized in unfolded maps. The laminar distribution of each projection is presented with color-coded arrows in the boxes located under each unfolded map (areas rostral to level –4.16 are referred to as 35* and 36*). Note that the lateral nucleus innervates mainly layers I–V of the perirhinal and postrhinal cortices, whereas the accessory basal nucleus innervates mainly layer V of area 35. The orientation of unfolded maps is indicated by arrows on the right (C = caudal, D = dorsal, R = rostral, and V = ventral). (4) A combined unfolded map of the perirhinal, postrhinal, and entorhinal cortices demonstrating the main projections (arrows) from the perirhinal and postrhinal cortices to the entorhinal cortex [entorhinal subfields: AE, CE, DIE, DLE, ME and VIE; adapted from Insausti et al. and Burwell and Amaral (Insausti et al., 1997; Burwell and Amaral, 1998)]. (5) The monosynaptic inputs from the lateral, basal and accessory basal nuclei of the amygdala to the entorhinal, perirhinal and postrhinal cortices (indicated with color-coded dots) are superimposed on projections from the perirhinal and postrhinal cortices to the entorhinal cortex (arrows). Amygdaloid inputs to the perirhinal cortex overlap with those regions of the perirhinal cortex that project to the DLE and DIE subfields of the entorhinal cortex, which project to the septal and midseptotemporal levels of the hippocampus, thus providing the amygdala with disynaptic access to the septal hippocampus. The monosynaptic amygdaloid inputs to the entorhinal cortex, however, terminate most heavily in the entorhinal subfields that innervate the temporal half of the hippocampus. (6) The three entorhinal segments projecting to the septal, midseptotemporal or temporal levels of the hippocampus are marked with different gray shadings [according to Dolorfo and Amaral (Dolorfo and Amaral, 1998)]. (7) The amygdala also monosynaptically innervates the hippocampus proper (the temporal end of the CA3, CA1) and the subiculum and the parasubiculum [origin of the inputs are written with color-coded lettering in the box; data from Pikkarainen et al. (Pikkarainen et al., 1999)].

Figure 9.

 A schematic line drawing summarizing the interconnections between the lateral, basal, or accessory basal nuclei of the amygdala with the hippocampal and parahippocampal areas. (1) The deep amygdaloid nuclei or their subdivisions receive information from various components of the hippocampal and parahippocampal areas [for review see Pitkänen et al. (Pitkänen et al., 2000)]. (2) Intra-amygdaloid circuitries (arrows indicate the main projections) distribute the incoming signals via parallel and serial routes to one or more amygdaloid region (adapted from Pitkänen et al., 1997). (3) The lateral, basal and accessory basal nuclei provide substantial projections to the perirhinal and postrhinal cortices, particularly to area 35, ventral area 36 and the ventral postrhinal cortex, which are summarized in unfolded maps. The laminar distribution of each projection is presented with color-coded arrows in the boxes located under each unfolded map (areas rostral to level –4.16 are referred to as 35* and 36*). Note that the lateral nucleus innervates mainly layers I–V of the perirhinal and postrhinal cortices, whereas the accessory basal nucleus innervates mainly layer V of area 35. The orientation of unfolded maps is indicated by arrows on the right (C = caudal, D = dorsal, R = rostral, and V = ventral). (4) A combined unfolded map of the perirhinal, postrhinal, and entorhinal cortices demonstrating the main projections (arrows) from the perirhinal and postrhinal cortices to the entorhinal cortex [entorhinal subfields: AE, CE, DIE, DLE, ME and VIE; adapted from Insausti et al. and Burwell and Amaral (Insausti et al., 1997; Burwell and Amaral, 1998)]. (5) The monosynaptic inputs from the lateral, basal and accessory basal nuclei of the amygdala to the entorhinal, perirhinal and postrhinal cortices (indicated with color-coded dots) are superimposed on projections from the perirhinal and postrhinal cortices to the entorhinal cortex (arrows). Amygdaloid inputs to the perirhinal cortex overlap with those regions of the perirhinal cortex that project to the DLE and DIE subfields of the entorhinal cortex, which project to the septal and midseptotemporal levels of the hippocampus, thus providing the amygdala with disynaptic access to the septal hippocampus. The monosynaptic amygdaloid inputs to the entorhinal cortex, however, terminate most heavily in the entorhinal subfields that innervate the temporal half of the hippocampus. (6) The three entorhinal segments projecting to the septal, midseptotemporal or temporal levels of the hippocampus are marked with different gray shadings [according to Dolorfo and Amaral (Dolorfo and Amaral, 1998)]. (7) The amygdala also monosynaptically innervates the hippocampus proper (the temporal end of the CA3, CA1) and the subiculum and the parasubiculum [origin of the inputs are written with color-coded lettering in the box; data from Pikkarainen et al. (Pikkarainen et al., 1999)].

We thank Ms Merja Lukkari for excellent histologic assistance and Ms Eija Antikainen for photographic processing. Also, the expert help of Dr Rebecca Burwell in defining the cytoarchitectonic borders of the perirhinal and postrhinal cortices is greatly appreciated. This study was supported by the Academy of Finland, the Vaajasalo Foundation, the Sigrid Juselius Foundation, the Finnish-Norwegian Medicine Foundation, and the Research and Science Foundation of Farmos.

References

Amaral DG, Price JL, Pitkänen A, Carmichael ST (1992) Anatomical organization of the primate amygdaloid complex. In: The amygdala: neurobiological aspects of emotion, memory, and mental dysfunction (Aggleton JP, ed.), pp. 1–66. New York: Wiley-Liss.
Arnault P, Roger M (
1990
) Ventral temporal cortex in the rat: connections of secondary auditory areas Te2 and Te3.
J Comp Neurol
 
302
:
110
–123.
Burwell RD (
2000
) The parahippocampal region: corticocortical connectivity.
Ann NY Acad Sci
 
911
:
25
–42.
Burwell RD, Amaral DG (
1998
) Perirhinal and postrhinal cortices of the rat: interconnectivity and connections with the entorhinal cortex.
J Comp Neurol
 
391
:
293
–321.
Burwell RD, Witter MP, Amaral DG (
1995
) Perirhinal and postrhinal cortices of the rat: a review of the neuroanatomical literature and comparison with findings from the monkey brain.
Hippocampus
 
5
:
390
–408.
Cahill L, McGaugh JL (
1998
) Mechanisms of emotional arousal and lasting declarative memory.
Trends Neurosci
 
21
:
294
–299.
Deacon TW, Eichenbaum H, Rosenberg P, Eckmann KW (
1983
) Afferent connections of the perirhinal cortex in the rat.
J Comp Neurol
 
220
:
168
–190.
Dolorfo CL, Amaral DG (
1998
) Entorhinal cortex of the rat: topographic organization of the cells of origin of the perforant path projection to the dentate gyrus.
J Comp Neurol
 
398
:
25
–48.
Gerfen CR, Sawchenko PE (
1984
) An anterograde neuroanatomical tracing method that shows the detailed morphology of neurons, their axons and terminals: immunohistochemical localization of an axonally transported plant lectin, Phaseolus vulgaris leucoagglutinin (PHA-L).
Brain Res
 
290
:
219
–238.
Gloor P (1992) Role of the amygdala in temporal lobe epilepsy. In: The amygdala: neurobiological aspects of emotion, memory, and mental dysfunction (Aggleton JP, ed.), pp. 505–538. New York: Wiley-Liss.
Hamann SB, Ely TD, Grafton ST, Kilts CD (
1999
) Amygdala activity related to enhanced memory for pleasant and aversive stimuli.
Nature Neurosci
 
2
:
289
–293.
Ikegaya Y, Saito H, Abe K (
1994
) Attenuated hippocampal long-term potentiation in basolateral amygdala-lesioned rats.
Brain Res
 
656
:
157
–164.
Ikegaya Y, Saito H, Abe K (
1995
) High-frequency stimulation of the basolateral amygdala facilitates the induction of long-term potentiation in the dentate gyrus in vivo.
Neurosci Res
 
22
:
203
–207.
Ikegaya Y, Saito H, Abe K (
1996
) Dentate gyrus field potentials evoked by stimulation of the basolateral amygdaloid nucleus in anesthetized rats.
Brain Res
 
718
:
53
–60.
Insausti R, Herrero MT, Witter MP (
1997
) Entorhinal cortex of the rat: cytoarchitectonic subdivisions and the origin and distribution of cortical efferents.
Hippocampus
 
7
:
146
–183.
Kosel KC, Van Hoesen GW, Rosene DL (
1983
) A direct projection from the perirhinal cortex (area 35) to the subiculum in the rat.
Brain Res
 
269
:
347
–351.
Krettek JE, Price JL (
1977
) Projections from the amygdaloid complex and adjacent olfactory structures to the entorhinal cortex and to the subiculum in the rat and cat.
J Comp Neurol
 
172
:
723
–752.
Krettek JE, Price JL (
1977
) Projections from the amygdaloid complex to the cerebral cortex and thalamus in the rat and cat.
J Comp Neurol
 
172
:
687
–722.
McDonald AJ, Jackson TR (
1987
) Amygdaloid connections with posterior insular and temporal cortical areas in the rat.
J Comp Neurol
 
262
:
59
–77.
McGaugh JL (
2000
) Memory — a century of consolidation.
Science
 
287
:
248
–251.
McIntyre DC, Kelly ME, Staines WA (
1996
) Efferent projections of the anterior perirhinal cortex in the rat.
J Comp Neurol
 
369
:
302
–318.
Naber PA, Caballero-Bleda M, Jorritsma-Byham B, Witter MP (
1997
) Parallel input to the hippocampal memory system through periand postrhinal cortices.
NeuroReport
 
8
:
2617
–2621.
Naber PA, Witter MP, Lopes da Silva FH (
1999
) Perirhinal cortex input to the hippocampus in the rat: evidence for parallel pathways, both direct and indirect. A combined physiological and anatomical study.
Eur J Neurosci
 
11
:
4119
–4133.
Ottersen OP (
1982
) Connections of the amygdala of the rat. IV. Corticoamygdaloid and intraamygdaloid connections as studied with axonal transport of horseradish peroxidase.
J Comp Neurol
 
205
:
30
–48.
Packard MG, Cahill L, McGaugh JL (
1994
) Amygdala modulation of hippocampal-dependent and caudate nucleus-dependent memory processes.
Proc Natl Acad Sci USA
 
91
:
8477
–8481.
Packard MG, Teather LA (
1998
) Amygdala modulation of multiple memory systems: hippocampus and caudate-putamen.
Neurobiol Learn Mem
 
69
:
163
–203.
Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. New York: Academic Press.
Petrovich GD, Risold PY, Swanson LW (
1996
) Organization of projections from the basomedial nucleus of the amygdala: a PHAL study in the rat.
J Comp Neurol
 
374
:
387
–420.
Pikkarainen M, Rönkkö S, Savander V, Insausti R, Pitkänen A (
1999
) Projections from the lateral, basal, and accessory basal nuclei of the amygdala to the hippocampal formation in rat.
J Comp Neurol
 
403
:
229
–260.
Pitkänen A, Jolkkonen E, Kemppainen S (
2000
) Anatomic heterogeneity of the rat amygdaloid complex.
Folia Morphol
 
59
:
1
–23.
Pitkänen A, Savander V, LeDoux JE (
1997
) Organization of intraamygdaloid circuitries in the rat: an emerging framework for understanding functions of the amygdala.
Trends Neurosci
 
20
:
517
–523.
Pitkänen A, Stefanacci L, Farb CR, Go G-G, LeDoux JE, Amaral DG (
1995
) Intrinsic connections of the rat amygdaloid complex: projections originating in the lateral nucleus.
J Comp Neurol
 
356
:
288
–310.
Price JL, Russchen FT, Amaral DG (1987) The limbic region. II. The amygdaloid complex. In: Handbook of chemical neuroanatomy. Vol. 5. Integrated systems of the CNS, Part I (Björklund A, Hökfelt T, Swanson LW, eds), pp. 279–388. Amsterdam: Elsevier.
Romanski LM, LeDoux JE (
1993
) Information cascade from primary auditory cortex to the amygdala: corticocortical and corticoamygdaloid projections of temporal cortex in the rat.
Cereb Cortex
 
3
:
515
–532.
Roozendaal B, McGaugh JL (
1997
) Basolateral amygdala lesions block the memory-enhancing effect of glucocorticoid administration in the dorsal hippocampus of rats.
Eur J Neurosci
 
9
:
76
–83.
Ruth RE, Collier TJ, Routtenberg A (
1982
) Topography between the entorhinal cortex and the dentate septotemporal axis in rats. I. Medial and intermediate entorhinal projecting cells.
J Comp Neurol
 
209
:
69
–78.
Ruth RE, Collier TJ, Routtenberg A (
1988
) Topographical relationship between the entorhinal cortex and the septotemporal axis of the dentate gyrus in rats. II. Cells projecting from lateral entorhinal subdivisions.
J Comp Neurol
 
270
:
506
–516.
Savander V, Go C-G, LeDoux JE, Pitkänen A (
1995
) Intrinsic connections of the rat amygdaloid complex: projections originating in the basal nucleus.
J Comp Neurol
 
361
:
345
–368.
Savander V, Go C-G, LeDoux JE, Pitkänen A (
1996
) Intrinsic connections of the rat amygdaloid complex: projections originating in the accessory basal nucleus.
J Comp Neurol
 
374
:
291
–313.
Scharfman HE, Witter MP, Schwarcz R (
2000
) Preface.
Ann NY Acad Sci USA
 
911
:
ix
–xiii.
Shi CJ, Cassell MD (
1999
) Perirhinal cortex projections to the amygdaloid complex and hippocampal formation in the rat.
J Comp Neurol
 
406
:
299
–328.
Squire LR, Zola-Morgan S (
1991
) The medial temporal lobe memory system.
Science
 
253
:
1380
–1386.
Stefanacci L, Suzuki WA, Amaral DG (
1996
) Organization of connections between the amygdaloid complex and the perirhinal and parahippocampal cortices in macaque monkeys.
J Comp Neurol
 
375
:
552
–582.
Van Essen DC, Maunsell JHR (
1980
) Two-dimensional maps of the cerebral cortex.
J Comp Neurol
 
191
:
255
–281.
Witter MP, Groenewegen HJ, Lopes da Silva FH, Lohman AHM (
1989
) Functional organization of the extrinsic and intrinsic circuitry of the parahippocampal region.
Prog Neurobiol
 
33
:
161
–253.