Neural Reorganization Due to Neonatal Amygdala Lesions in the Rhesus Monkey: Changes in Morphology and Network Structure.

It is generally believed that neural damage that occurs early in development is associated with greater adaptive capacity relative to similar damage in an older individual. However, few studies have surveyed whole brain changes following early focal damage. In this report, we employed multimodal magnetic resonance imaging analyses of adult rhesus macaque monkeys who had previously undergone bilateral, neurotoxic lesions of the amygdala at about 2 weeks of age. A deformation-based morphometric approach demonstrated reduction of the volumes of the anterior temporal lobe, anterior commissure, basal ganglia, and pulvinar in animals with early amygdala lesions compared to controls. In contrast, animals with early amygdala lesions had an enlarged cingulate cortex, medial superior frontal gyrus, and medial parietal cortex. Diffusion-weighted imaging tractography and network analysis were also used to compare connectivity patterns and higher-level measures of communication across the brain. Using the communicability metric, which integrates direct and indirect paths between regions, lesioned animals showed extensive degradation of network integrity in the temporal and orbitofrontal cortices. This work demonstrates both degenerative as well as progressive large-scale neural changes following long-term recovery from neonatal focal brain damage.

Emergence of stereotypies in juvenile monkeys (Macaca mulatta) with neonatal amygdala or hippocampus lesions.

The emergence of stereotypies was examined in juvenile rhesus monkeys (Macaca mulatta) who, at 2 weeks of postnatal age, received selective bilateral ibotenic acid lesions of the amygdala (N = 8) or hippocampus (N = 8). The lesion groups were compared to age-matched control subjects that received a sham surgical procedure (N = 8). All subjects were maternally reared for the first 6 months and provided access to social groups throughout development. Pronounced stereotypies were not observed in any of the experimental groups during the first year of life. However, between 1 to 2 years of age, both amygdala- and hippocampus-lesioned subjects began to exhibit stereotypies. When observed as juveniles, both amygdala- and hippocampus-lesioned subjects consistently produced more stereotypies than the control subjects in a variety of contexts. More interesting, neonatal lesions of either the amygdala or hippocampus resulted in unique repertoires of repetitive behaviors. Amygdala-lesioned subjects exhibited more self-directed stereotypies and the hippocampus-lesioned subjects displayed more head-twisting. We discuss these results in relation to the neurobiological basis of repetitive stereotypies in neurodevelopmental disorders, such as autism.

Individual differences in the cognitive and neurobiological consequences of normal aging.

Defining the neural basis of age-related cognitive dysfunction is a major goal of current research on aging. Compelling evidence from laboratory animals and humans indicates that aging does not inevitably lead to cognitive decline. Conducting neurobiological investigations in subjects that have previously undergone behavioral characterization has therefore emerged as a promising strategy for identifying those alterations in brain structure and function that are specifically associated with age-related cognitive impairment.

Emerging principles of intrinsic hippocampal organization.

The hippocampal formation has a unique and highly distributed network of intrinsic connections. What are the principles of organization that govern information flow through this system? The notion that information processing in the hippocampal formation is segregated in autonomous chips or lamellae appears to be inconsistent with the extremely divergent nature of many of the intrinsic connections. Recent neuroanatomical data suggest, however, that information may be segregated in other ways as it negotiates the links from one hippocampal region to the next.

The expression of social dominance following neonatal lesions of the amygdala or hippocampus in rhesus monkeys (Macaca mulatta).

As part of ongoing studies on the neurobiology of socioemotional behavior in the nonhuman primate, the authors examined the social dominance hierarchy of juvenile macaque monkeys (Macaca mulatta) that received bilateral ibotenic acid lesions of the amygdala or the hippocampus or a sham surgical procedure at 2 weeks of age. The subjects were reared by their mothers with daily access to large social groups. Behavioral observations were conducted while monkeys were given access to a limited preferred food. This testing situation reliably elicited numerous species-typical dominance behaviors. All subjects were motivated to retrieve the food when tested individually. However, when a group of 6 monkeys was given access to only 1 container of the preferred food, the amygdala-lesioned monkeys had less frequent initial access to the food, had longer latencies to obtain the food, and demonstrated fewer species-typical aggressive behaviors. They were thus lower ranking on all indices of social dominance. The authors discuss these findings in relation to the role of the amygdala in the establishment of social rank and the regulation of aggression and fear.

Reduction in opioid- and cannabinoid-induced antinociception in rhesus monkeys after bilateral lesions of the amygdaloid complex.

The amygdaloid complex is a prominent temporal lobe region that is associated with "emotional" information processing. Studies in the rodent have also recently implicated the amygdala in the processing and modulation of pain sensation, the experience of which involves a considerable emotional component in humans. In the present study, we sought to establish the relevance of the amygdala to pain modulation in humans by investigating the contribution of this region to antinociceptive processes in nonhuman primates. Using magnetic resonance imaging guidance, the amygdaloid complex was lesioned bilaterally in six rhesus monkeys (Macaca mulatta) through microinjection of the neurotoxin ibotenic acid. This procedure resulted in substantial neuronal cell loss in all nuclear subdivisions of this structure. In awake unoperated control monkeys, systemic administration of the prototypical opioid morphine or the cannabinoid receptor agonist WIN55,212-2 produced dose-dependent antinociception on a warm-water tail-withdrawal assay. The antinociceptive effects of each drug were reversible with an appropriate antagonist. In monkeys with bilateral amygdala lesions, however, the antinociceptive effects of each drug were significantly reduced. These results constitute the first causal data demonstrating the necessity of neurons in a specific brain region for the full expression of opioid- and cannabinoid-induced antinociception in the primate. Because our amygdala-lesioned monkeys exhibited both a reduction in antinociception and a reduction in behavioral indices of fear (Emery et al., 2001), the possibility should be considered that, in the primate, "antinociceptive circuitry" and "fear circuitry" overlap at the level of the amygdala.

The development of mother-infant interactions after neonatal amygdala lesions in rhesus monkeys.

As part of ongoing studies on the neurobiology of socioemotional behavior in the nonhuman primate, we examined the development of mother-infant interactions in 24 macaque monkeys who received either bilateral amygdala or hippocampus ibotenic acid lesions, or a sham surgical procedure at 2 weeks of age. After surgery, the infants were returned to their mothers and reared with daily access to small social groups. Behavioral observations of the infants in dyads (mother-infant pairs alone), tetrads (two mother-infant pairs), and social groups (six mother-infant pairs and one adult male) revealed species-typical mother-infant interactions for all lesion conditions, with the exception of increased physical contact time between the amygdala-lesioned infants and their mothers. Immediately after permanent separation from their mothers at 6 months of age, the infants were tested in a mother preference test that allowed the infants to choose between their mother and another familiar adult female. Unlike control and hippocampus-lesioned infants, the amygdala-lesioned infants did not preferentially seek proximity to their mother, nor did they produce distress vocalizations. Given the normal development of mother-infant interactions observed before weaning, we attribute the behavior of the amygdala-lesioned infants during the preference test to an impaired ability to perceive potential danger (i.e., separation from their mother in a novel environment), rather than to a disruption of the mother-infant relationship. These results are consistent with the view that the amygdala is not essential for fundamental aspects of social behavior but is necessary to evaluate potentially dangerous situations and to coordinate appropriate behavioral responses.

The distribution of serotonergic fibers in the macaque monkey amygdala: an immunohistochemical study using antisera to 5-hydroxytryptamine.

Though both the amygdala and the serotonin system appear to play critical roles in regulating fear and anxiety, little is known regarding the organization of serotonergic inputs to the primate amygdala. The present study employed immunohistochemistry to determine the distribution of serotonin fibers in the macaque amygdala. The brains of three adult male Macaca fascicularis monkeys were prepared for histological analysis using a polyclonal antibody to serotonin. The macaque amygdala is densely innervated by serotonergic fibers and demonstrates a distinctive pattern of fiber distribution and density among the 13 nuclei and cortical areas. The highest density of 5-hydroxytryptamine immunoreactive fibers is observed in the central nucleus, the nucleus of the lateral olfactory tract, the paralaminar nucleus, the anterior amygdaloid area and a small region of the amygdalohippocampal area. Moderate fiber densities are found in portions of the basal, lateral, and intercalated nuclei. The lowest fiber densities are observed in the accessory basal, posterior cortical, anterior cortical and medial nuclei, and in subregions of the periamygdaloid cortex. The present study provides evidence that the serotonergic system can have substantial influence on the ongoing activity of the amygdaloid complex.

Morphological characteristics and electrophysiological properties of CA1 pyramidal neurons in macaque monkeys.

Little is known about the morphological characteristics and intrinsic electrophysiological properties of individual neurons in the nonhuman primate hippocampus. We have used intracellular recording and biocytin-labeling techniques in the in vitro hippocampal slice preparation to provide quantitative evaluation of the fundamental morphological and intrinsic electrophysiological characteristics of macaque monkey CA1 pyramidal neurons. These neurons have previously been studied in the rat in our laboratory. Monkey CA1 pyramidal neurons have an average soma volume of 3578 microm3, 4.71 basal dendrites with 53 terminal branches for a dendritic length of about 10,164 microm, 1.13 apical dendrites with 47 terminal branches for a dendritic length of about 10,678 microm. In comparison, rat CA1 pyramidal neurons have an average soma volume of 2066 microm3, 3.35 basal dendrites with 29 terminal branches for a dendritic length of about 4,586 microm, 1.43 apical dendrites with 62 terminal branches for a dendritic length of about 8,838 microm. The basic intrinsic electrophysiological properties of CA1 pyramidal cells are similar in monkeys and rats. Monkey CA1 pyramidal neurons have a resting membrane potential of about -62 mV (rat: -62 mV), an input resistance of 35 MOmega (rat: 34-49 MOmega), a rheobase of 0.17 nA (rat: 0.12-0.20 nA) and an action potential amplitude of 83 mV (rat: 71-89 mV). Although morphological differences such as the increased dendritic length may translate into differences in neural processing between primates and rodents, the functional significance of these morphological differences is not yet clear. Quantitative studies of the primate brain are critical in order to extrapolate information derived from rodent studies into better understanding of the normal and pathological function of the human hippocampus.

The amygdala and autism: implications from non-human primate studies.

Brothers (1990) has proposed that the amygdala is an important component of the neural network that underlies social behavior. Kemper and Bauman (1993) identified neuropathology in the amygdala of the postmortem autistic brain. These findings, along with recent functional neuroimaging data, have led Baron-Cohen et al. (2000) to propose that dysfunction of the amygdala may be responsible, in part, for the impairment of social behavior that is a hallmark feature of autism. Recent data from studies in our laboratory on the effects of amygdala lesions in the adult and infant macaque monkey do not support a fundamental role for the amygdala in social behavior. If the amygdala is not essential for the component processes of social behavior, as seems to be case in both non-human primates and selected patients with bilateral amygdala damage, then it is unlikely to be the primary substrate for the impaired social behavior of autism. However, damage to the amygdala does have an effect on a monkey's response to normally fear-inducing stimuli, such as snakes, and removes a natural reluctance to engage novel conspecifics in social interactions. These findings lead to the conclusion that an important role for the amygdala is in the detection of threats and mobilizing an appropriate behavioral response, part of which is fear. Interestingly, an important comorbid feature of autism is anxiety (Muris et al. 1998). If the amygdala is pathological in subjects with autism, it may contribute to their abnormal fears and increased anxiety rather than their abnormal social behavior.

Recognition memory deficits in a subpopulation of aged monkeys resemble the effects of medial temporal lobe damage.

The present study examined individual differences in recognition memory function in a group of Old World monkeys (Macaca mulatta). Four young (9-11 years) and 10 aged (22-33 years) monkeys were tested in the same delayed-nonmatching-to-sample (DNMS) recognition memory procedure that has been widely used to study the effects of experimental hippocampal lesions in young subjects. Animals were first trained to a 90% correct learning criterion in the DNMS task using a 10-second delay between the sample and recognition phase of each trial. The memory demands of the task were then increased by gradually extending the retention interval from 15 seconds to 10 minutes. Three of the aged monkeys performed as accurately as young subjects at all delays. The remaining aged monkeys performed well at the shortest delays (15 and 30 seconds), but progressively greater impairments emerged across delays of 60 seconds, 2 minutes, and 10 minutes. These results suggest that recognition memory is only compromised in a subpopulation of aged monkeys. Moreover, aged monkeys that are impaired in the DNMS task exhibit the same delay-dependent pattern of deficits that is the hallmark of memory dysfunction resulting from medial temporal lobe damage.

A Golgi study of cell types in the hilar region of the hippocampus in the rat.

The morphology of neurons in the "hilar region" of the hippocampus (fields CA3c and CA4 of Lorente de Nó, '34) was analyzed with several variants of the Golgi technique. Hippocampi were dissected from the brains of 28-day-old rats, fixed and impregnated by immersion, and sectioned perpendicular to the long axis. Based on the resident cell types, aspects of the neuropil, and published data related to afferent termination, the area under study was divided into four zones. At least 21 cell types were observed throughout these zones, several of which had not previously been described. Many cells in this area exhibited an impressive number and variety of dendritic and axonal appendages, including spines on the proximal portion of some axons. The close apposition of fibers to these axonal spines suggested the possibility of axo-axonal interactions. The influence of dentate granule cells, through their mossy fibers, on the synaptic economy of the "hilar region" was found to be more extensive than previously reported. Mossy fibers appeared to terminate on the dendrites of several types of non-pyramidal cells, which bear no thorny excrescences, by means of thin filiform extensions which emanate from the mossy fiber expansions and by means of thin mossy fiber collaterals which are devoid of typical expansions. Consideration is given to a long-standing debate as to whether the deep "hilar region" (CA4 of Lorente de Nó, '34, hilus of the fascia dentata of Blackstad, '56) is related more to the hippocampus or to the fascia dentata and it is concluded that the deep hilar region is an area of mergence of the polymorphic zones of these two cortical structures. The results of the present study do not support the proposition that the deep hilar region is an extension of the pyramidal layer of the hippocampus as suggested by Lorente de Nó ('34), and thus CA4 is a misnomer. Rather, the cells in this area are most closely related to the fascia dentata and should thus be considered to lie in the polymorphic zone of "area dentata" as proposed initially by Blackstad ('56).

Subcortical afferents to the hippocampal formation in the monkey.

The distribution of neurons in the basal telencephalon, the diencephalon, and the brainstem that project to the hippocampal formation has been analyzed in mature cynomolgus monkeys (Macaca fascicularis) by the injection of horseradish peroxidase into different rostro-caudal levels of the hippocampal formation. After injections which involve Ammon's horn, the dentate gyrus, and the subicular complex, retrogradely labeled neurons are found in the following regions: in the amygdala (specifically in the anterior amygdaloid area, the basolateral nucleus, and the periamygdaloid cortex); in the medial septal nucleus and the nucleus of the diagonal band; in the ventral part of the claustrum; in the substantia innominata and the basal nucleus of Meynert; in the rostral thalamus (specifically in the anterior nuclear complex, the laterodorsal nucleus, the paraventricular and parataenial nuclei, the nucleus reuniens, and the nucleus centralis medialis); in the lateral preoptic and lateral hypothalamic areas, and especially in the supramammillary and retromammillary regions; in the ventral tegmental area, the tegmental reticular fields, the raphe nuclei (specifically in nucleus centralis superior and the dorsal raphe nucleus), in the nucleus reticularis tegmenti pontis, the central gray, the dorsal tegmental nucleus, and in the locus coeruleus.

Distribution of reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) cells and fibers in the monkey amygdaloid complex.

The NADPH-d histochemical method stains a selective population of neurons in the central nervous system. Although the functional significance of the enzyme in these cells is unknown, it has nonetheless proved to be a useful marker. In the present study we describe the distribution of NADPH-d-positive cells and fibers in the amygdaloid complex of the Macaca fascicularis monkey. NADPH-d-positive neurons were distributed throughout the amygdaloid complex. Based on the intensity of the reaction product, three different types of NADPH-d-positive cells were described: type 1 cells, the most intensely stained, varied in morphology and were most commonly found in the accessory basal, basal, and lateral nuclei and in the nucleus of the lateral olfactory tract; type 2 cells, the most common NADPH-d-positive cells, were more lightly stained, were generally stellate in shape, and were found in the lateral, basal, and accessory basal nuclei; type 3 cells were very lightly stained, oval or round in shape, and mostly found in the medial, anterior cortical, and paralaminar nuclei. NADPH-d staining was also associated with axonal fiber plexuses in various regions of the amygdala. The highest densities of stained fibers were found in the lateral nucleus, the parvicellular portion of the accessory basal nucleus, and the anterior amygdaloid area. The lowest densities of NADPH-d-positive fiber staining were found in the amygdalohippocampal area, in the lateral part of the central nucleus, and in the intercalated nuclei. In addition to the neuronal and fiber staining, a diffuse, blue neuropil staining was also observed, most commonly in the anterior cortical nucleus, the medial nucleus, the intercalated nuclei, and especially in the amygdalohippocampal area. The distribution of NADPH-d staining often respected nuclear boundaries within the amygdala and was particularly helpful in clarifying the borders of the amygdalohippocampal area.

Entorhinal cortex of the monkey: V. Projections to the dentate gyrus, hippocampus, and subicular complex.

The topographic and laminar organization of entorhinal projections to the dentate gyrus, hippocampus, and subicular complex was investigated in the Macaca fascicularis monkey. Injections of 3H-amino acids were placed at various positions within the entorhinal cortex and the distribution of anterogradely labeled fibers and terminals within the other fields of the hippocampal formation was determined. Injections of the retrograde tracers Fast blue, Diamidino yellow, and wheat germ agglutinin-horseradish peroxidase (WGA-HRP) were also placed into the dentate gyrus, hippocampus, and subicular complex, and the distribution of retrogradely labeled cells in the entorhinal cortex was plotted using a computer-aided digitizing system. The entorhinal cortex gave rise to projections that terminated in the subiculum, in the CA1, CA2, and CA3 fields of the hippocampus, and in the dentate gyrus. Projections to the dentate gyrus, and fields CA3 and CA2 of the hippocampus, originated preferentially in layers II and VI of the entorhinal cortex whereas projections to CA1 and to the subiculum originated mainly in layers III and V. Anterograde tracing experiments demonstrated that all regions of the entorhinal cortex project to the outer two-thirds of the molecular layer of the dentate gyrus and to much of the radial extent of the stratum lacunosum-moleculare of CA3 and CA2. While the terminal distributions of entorhinal projections to the dentate gyrus, CA3, and CA2 were not as clearly laminated as in the rat, projections from rostral levels of the entorhinal cortex preferentially innervated the outer portion of the molecular layer and stratum lacunosum-moleculare, whereas more caudal levels of the entorhinal cortex projected relatively more heavily to the deeper portions of the entorhinal terminal zones. The entorhinal projection to the CA1 field of the hippocampus and to the subiculum followed a transverse rather than radial gradient of distribution. Rostral levels of the entorhinal cortex terminated most heavily at the border of CA1 and the subiculum. More caudal levels of the entorhinal cortex projected to progressively more distal portions of the subiculum (towards the presubiculum) and more proximal portions of CA1 (towards CA2). Lateral portions of the entorhinal cortex projected to caudal levels of the recipient fields and more medial parts of the entorhinal cortex projected to progressively more rostral portions of the fields.

An analysis of the origins of the cholinergic and noncholinergic septal projections to the hippocampal formation of the rat.

These experiments were directed at determining the proportion and distribution of cholinergic septal cells which project to the rat hippocampal formation. Injections of WGA-HRP were placed into different regions of the hippocampal formation and sections through the septal complex were processed for the simultaneous demonstration of the retrogradely transported marker and for choline acetyltransferase (ChAT) immunoreactivity. Preliminary analysis of adjacent normal series prepared either for the demonstration of ChAT or stained by the Nissl method demonstrated several distinct cell groups in the classically defined medial septal nucleus and vertical limb of the nucleus of the diagonal band. The groups of cells ranged from almost entirely ChAT-positive to entirely noncholinergic. On the basis of shape and size of the constituent cells, the ChAT-positive cells of the septal complex were divided into dorsal, intermediate, and ventral subdivisions. The proportion of retrogradely labeled cells that were also ChAT positive ranged from 22.8% to 77.4% in different experiments. When only the hippocampus and dentate gyrus are considered, this variation can largely be accounted for by the topographic organization of the septohippocampal projection. The medial, noncholinergic half of the medial septal nucleus projects primarily to the rostral or septal portions of the dentate gyrus and hippocampus, whereas the lateral half, in which the dorsal ChAT group is located, projects heavily to more temporal levels. Rostral portions of the hippocampus and dentate gyrus receive most of their cholinergic input from the ventral ChAT cell group which forms a major component of the vertical limb of the nucleus of the diagnoal band. While some ChAT-positive cells in the intermediate group project to the hippocampal formation, they are generally less numerous than those from the dorsal and ventral groups. However, in a control experiment in which the WGA-HRP injection was placed into the cingulate cortex overlying the rostral hippocampal formation, the intermediate ChAT group accounted for 71.2% of the double-labeled cells.

Distribution of parvalbumin-immunoreactive cells and fibers in the monkey temporal lobe: the amygdaloid complex.

The calcium-binding protein parvalbumin was immunohistochemically localized in the monkey amygdaloid complex. Parvalbumin-immunoreactive neuronal cell bodies, fibers, and terminals were observed in several amygdaloid nuclei and cortical areas. Three types of aspiny neurons, ranging from small spherical cells (Type 1) to large multipolar cells (Type 2) and fusiform cells (Type 3) were observed in most amygdaloid regions, though the proportions of the cell types were different in each region. The density of parvalbumin-immunoreactive fibers and terminals tended to parallel the density of labeled cell bodies. The highest densities of parvalbumin profiles were observed in the nucleus of the lateral olfactory tract, the periamygdaloid cortex (PAC2), the magnocellular division of the basal nucleus, the ventrolateral portion of the lateral nucleus, and the accessory basal nucleus. The regions containing the lowest densities of parvalbumin-positive profiles were the medial nucleus, anterior cortical nucleus, central nucleus, and the paralaminar nucleus. In regions with fiber and terminal labeling, pericellular networks of fibers, reminiscent of basket cell terminations, were commonly observed to surround unstained neuronal cell bodies and proximal dendrites. In the magnocellular division of the basal nucleus, and to a lesser extent in the lateral nucleus, parvalbumin-labeled "cartridges" of axo-axonic terminals were observed on the initial segments of unlabeled cells. Parvalbumin-positive varicosities were also commonly observed in close apposition to the soma and dendrites of parvalbumin-immunoreactive cells. Given the close correspondence between the distribution of parvalbumin-positive neurons and a subset of GABAergic neurons in many brain regions, these data provide a first indication of the organization of the inhibitory circuitry of the primate amygdaloid complex.

Distribution of parvalbumin-immunoreactive cells and fibers in the monkey temporal lobe: the hippocampal formation.

The distribution of parvalbumin-immunoreactive cells and fibers in the various fields of the hippocampal formation was studied in the macaque monkey. Parvalbumin-immunoreactive neurons had aspiny or sparsely spiny dendrites that often had a beaded appearance; most resembled classically identified interneurons. Parvalbumin-immunoreactive fibers and terminals were confined to certain laminae in each field and generally had a pericellular distribution. In the dentate gyrus, there was a dense pericellular plexus of immunoreactive terminals in the granule cell layer. Except for a narrow supragranular zone, there was a marked paucity of terminals in the molecular and polymorphic cell layers. Immunoreactive neurons were mainly located immediately subjacent to the granule cell layer and comprised a variety of morphological cell types. The three fields of the hippocampus proper (CA3, CA2, and CA1) demonstrated differences in their parvalbumin staining characteristics. In CA3, there was a prominent pericellular terminal plexus in the pyramidal cell layer that was densest distally (closer to CA2). Immunoreactive cells were located either in the pyramidal cell layer, where many had a pyramidal shape and prominent apical and basal dendrites, or in stratum oriens. CA2 had a staining pattern similar to that in CA3, though both the number of labeled cells and the density of the pericellular terminal plexus were greater in CA2. In CA1, there was a markedly lower number of parvalbumin-labeled cells than in CA3 and CA2 and the cells tended to be located in the deep part of the pyramidal cell layer or in stratum oriens. The pyramidal cell layer of CA1 contained a pericellular terminal plexus that was substantially less dense than in CA3 and CA2. At the border between CA1 and the subiculum there was a marked increase in the number of parvalbumin-immunoreactive neurons. The positive cells were scattered throughout the pyramidal cell layer of the subiculum and comprised a variety of sizes and shapes. Terminal labeling was higher in the pyramidal cell layer of the subiculum than in CA1. Layer II of the presubiculum had one of the highest densities of fiber and terminal labeling in the hippocampal formation. The density of staining was lower in the superficial portion of the layer where linear cartridges of presumed axo-axonic synapses were common. A large number of parvalbumin-immunoreactive cells were scattered throughout layer II of the presubiculum; small, spherical, multipolar cells were commonly observed in layer I. The parasubiculum had a somewhat lower density of positive cells and fibers than the presubiculum.(ABSTRACT TRUNCATED AT 400 WORDS)

Cholinergic innervation of the monkey amygdala: an immunohistochemical analysis with antisera to choline acetyltransferase.

The organization of the cholinergic innervation of the macaque monkey amygdaloid complex was investigated by means of immunohistochemical techniques and either a polyclonal antiserum or a monoclonal antibody directed against the specific synthetic enzyme choline acetyltransferase (ChAT). Adjacent series of sections were processed histochemically for the demonstration of the degradative enzyme acetylcholinesterase (AChE) or for cell bodies with thionin. The density of ChAT immunoreactivity differed substantially among the various nuclei and cortical regions of the amygdala. In general, the distribution of ChAT immunoreactivity paralleled the pattern of AChE staining. One notable exception was the presence of AChE containing cell bodies in addition to AChE positive fibers within nearly all of the nuclear and cortical regions. In contrast, ChAT immunoreactivity was associated only with fibers and terminals. The highest density of ChAT immunoreactive fibers and terminals was consistently observed in the magnocellular subdivision of the basal nucleus. Staining was substantially less dense in the more ventrally situated parvicellular subdivision. Medially, in the adjacent accessory basal nucleus, immunoreactive fibers and terminals were densest in the magnocellular and superficial subdivisions and least prominent in the parvicellular subdivision. Of the deep nuclei, the lateral nucleus generally obtained the least ChAT immunoreactive terminals and processes. Only its more densely cellular ventrolateral portion contained appreciable fiber and terminal staining. One of the more distinctive patterns of ChAT immunoreactivity was seen in the nucleus of the lateral olfactory tract. Here, ChAT positive fibers formed pericellular basket plexuses around unstained cell bodies. This unique pattern of staining was used to delineate the boundaries of the nucleus and indicated that it is present for much of the rostrocaudal extent of the amygdala. Another region of conspicuous staining on the medial surface of the amygdala was the sulcal portion of the periamygdaloid cortex. This region, associated with the sulcus semiannularis and bordering the entorhinal cortex, consistently contained dense immunoreactivity. The central nucleus also presented a somewhat idiosyncratic pattern of ChAT staining. The lateral subdivision had a diffuse distribution of immunoreactivity in which focal patches of more densely stained terminals and occasional fine fibers were embedded. In contrast, the medial subdivision contained a larger number of thicker, stained fibers without diffuse background labeling.(ABSTRACT TRUNCATED AT 400 WORDS)

Perirhinal and parahippocampal cortices of the macaque monkey: cortical afferents.

Neuropsychological studies have recently demonstrated that the macaque monkey perirhinal (areas 35 and 36) and parahippocampal (areas TH and TF) cortices contribute importantly to normal memory function. Unfortunately, neuroanatomical information concerning the cytoarchitectonic organization and extrinsic connectivity of these cortical regions is meager. We investigated the organization of cortical inputs to the macaque monkey perirhinal and parahippocampal cortices by placing discrete injections of the retrograde tracers fast blue, diamidino yellow, and wheat germ agglutinin conjugated to horseradish peroxidase throughout these areas. We found that the macaque monkey perirhinal and parahippocampal cortices receive different complements of cortical inputs. The major cortical inputs to the perirhinal cortex arise from the unimodal visual areas TE and rostral TEO and from area TF of the parahippocampal cortex. The perirhinal cortex also receives projections from the dysgranular and granular subdivisions of the insular cortex and from area 13 of the orbitofrontal cortex. In contrast, area TF of the parahippocampal cortex receives its strongest input from more caudal visual areas V4, TEO, and caudal TE, as well as prominent inputs from polymodal association cortices, including the retrosplenial cortex and the dorsal bank of the superior temporal sulcus. Area TF also receives projections from areas 7a and LIP of the posterior parietal lobe, insular cortex, and areas 46, 13, 45, and 9 of the frontal lobe. As with area TF, area TH receives substantial projections from the retrosplenial cortex as well as moderate projections from the dorsal bank of the superior temporal sulcus; unlike area TF, area TH receives almost no innervation from areas TE and TEO. It does, however, receive relatively strong inputs from auditory association areas on the convexity of the superior temporal gyrus.