Biomedical subjects

D G Amaral

Publications and source records attributed to D G Amaral.

At least 19 recordsLinked to original sources

PubMed2006

Neural responses to facial expression and face identity in the monkey amygdala.

The amygdala is purported to play an important role in face processing, yet the specificity of its activation to face stimuli and the relative contribution of identity and expression to its activation are unknown. In the current study, neural activity in the amygdala was recorded as monkeys passively viewed images of monkey faces, human faces, and objects on a computer monitor. Comparable proportions of neurons responded selectively to images from each category. Neural responses to monkey faces were further examined to determine whether face identity or facial expression drove the face-selective responses. The majority of these neurons (64%) responded both to identity and facial expression, suggesting that these parameters are processed jointly in the amygdala. Large fractions of neurons, however, showed pure identity-selective or expression-selective responses. Neurons were selective for a particular facial expression by either increasing or decreasing their firing rate compared with the firing rates elicited by the other expressions. Responses to appeasing faces were often marked by significant decreases of firing rates, whereas responses to threatening faces were strongly associated with increased firing rate. Thus global activation in the amygdala might be larger to threatening faces than to neutral or appeasing faces.

Aggression↗

PubMed2006

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.

Aggression↗

PubMed2005

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.

Amygdala↗

PubMed2005

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.

Animals↗

PubMed2004

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.

Age Factors↗

PubMed2004

The development of social behavior following neonatal amygdala lesions in rhesus monkeys.

We examined the role of the amygdala in the development of nonhuman primate social behavior. Twenty-four rhesus monkeys received bilateral ibotenic acid lesions of either the amygdala or the hippocampus or received a sham surgical procedure at 2 weeks of age. Subjects were reared with their mothers and were provided daily access to social rearing cohorts. The subjects were weaned at 6 months of age and then observed while paired with familiar conspecifics at 6 and 9 months of age and with unfamiliar conspecifics at 1 year of age. The subjects were also observed during daily cohort socialization periods. Neither amygdala nor hippocampus lesions altered fundamental aspects of social behavior development. All subjects, regardless of lesion condition, developed a species-typical repertoire of social behavior and displayed interest in conspecifics during social encounters. The amygdala lesions, however, clearly affected behaviors related to fear processing. The amygdala-lesioned subjects produced more fear behaviors during social encounters than did control or hippocampus-lesioned subjects. Although the heightened fear response of the amygdala-lesioned subjects was consistent across different testing paradigms and was observed with both familiar and novel partners, it did not preclude social interactions. In fact, the amygdala-lesioned subjects displayed particular social behaviors, such as following, cooing, grunting, presenting to be groomed, and presenting to be mounted more frequently than either control or hippocampus-lesioned subjects. These findings are consistent with the view that the amygdala is not needed to develop fundamental aspects of social behavior and may be more related to the detection and avoidance of environmental dangers.

Amygdala↗

PubMed2003

Topographic organization of projections from the amygdala to the visual cortex in the macaque monkey.

The topography of amygdaloid projections to the visual cortices in the macaque monkey was examined by injecting the fluorescent tracers Fast Blue and Diamidino Yellow at different locations in the occipital and temporal lobes and mapping the distribution of retrogradely labeled cells in the amygdala. Injections involving regions from rostral area TE to caudal area V1 all resulted in labeled cells within the basal nucleus of the amygdala. Relatively few double-labeled cells were observed even when the two injections were separated by less than 3 mm. The projections were rostrocaudally organized such that projections to caudal visual areas originated from dorsal and caudal portions of the magnocellular division of the basal nucleus while projections to more rostrally situated visual areas originated in more rostral and ventral portions of the basal nucleus. When injections involved rostral and medial portions of area TE, retrogradely labeled cells were observed in the accessory basal and lateral nuclei in addition to the basal nucleus. These data confirm that the amygdala gives rise to feedback projections to all levels of the "ventral stream" visual pathway. The projections do not appear to be diffusely distributed since few double-labeled cells were observed. The largest cells of the basal nucleus, those located in the magnocellular division, project the farthest in the visual system and innervate all occipital and temporal levels. The smaller cells, in the intermediate and parvicellular regions, project to more rostral and medial portions of the visual cortex. These results suggest that the amygdala may have substantial modulatory control over sensory processing at all stages of the ventral-stream visual cortical hierarchy.

Amidines↗

PubMed2003

Where are the perirhinal and parahippocampal cortices? A historical overview of the nomenclature and boundaries applied to the primate medial temporal lobe.

Strong evidence has emerged over the last 15 years showing that the perirhinal and parahippocampal cortices play an important role in normal memory function. Despite our progress in understanding the mnemonic functions of these areas, controversy still exists concerning the precise location of the boundaries of these areas in the primate brain. To provide a context for understanding the current discrepancies in the literature, we present a historical overview of the different boundary schemes and nomenclatures that have been applied to the medial temporal lobe cortices in both humans and nonhuman primates. We describe how the boundaries and the names applied to these regions have evolved over time, starting with the classic cytoarchitectonisists working in the early 1900s, and ending with the various schemes being used in the contemporary literature. We show that the current controversies concerning the boundaries of the perirhinal and parahippocampal cortices can be traced directly to the classic cytoarchitectonic literature.

Anatomy↗

PubMed2003

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.

Amygdala↗

PubMed2001

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.

Amygdala↗

PubMed2001

Intracellular recording and labeling of mossy cells and proximal CA3 pyramidal cells in macaque monkeys.

Little is known about the morphological characteristics and intracellular electrophysiological properties of neurons in the primate hippocampus and dentate gyrus. We have therefore begun a program of studies using intracellular recording and biocytin labeling in hippocampal slices from macaque monkeys. In the current study, we investigated mossy cells and proximal CA3 pyramidal cells. As in rats, macaque mossy cells display fundamentally different traits than proximal CA3 pyramidal cells. Interestingly, macaque mossy cells and CA3 pyramidal neurons display some morphological differences from those in rats. Macaque monkey mossy cells extend more dendrites into the molecular layer of the dentate gyrus, have more elaborate thorny excrescences on their proximal dendrites, and project more axon collaterals into the CA3 region. In macaques, three types of proximal CA3 pyramidal cells are found: classical pyramidal cells, neurons with their dendrites confined to the CA3 pyramidal cell layer, and a previously undescribed cell type, the "dentate" CA3 pyramidal cell, whose apical dendrites extend into and ramify within the hilus, granule cell layer, and molecular layer of the dentate gyrus. The basic electrophysiological properties of mossy cells and proximal CA3 cells are similar to those reported for the rodent. Mossy cells have a higher frequency of large amplitude spontaneous depolarizing postsynaptic potentials, and proximal CA3 pyramidal cells are more likely to discharge bursts of action potentials. Although mossy cells and CA3 pyramidal cells in macaque monkeys display many morphological and electrophysiological features described in rodents, these findings highlight significant species differences, with more heterogeneity and the potential for richer interconnections in the primate hippocampus.

Animals↗

PubMed2001

Increased social fear and decreased fear of objects in monkeys with neonatal amygdala lesions.

The amygdala has been implicated in the mediation of emotional and species-specific social behavior (Kling et al., 1970; Kling and Brothers, 1992; Kluver and Bucy, 1939; Rosvold et al., 1954). Humans with bilateral amygdala damage are impaired in judging negative emotion in facial expressions and making accurate judgements of trustworthiness (Adolphs et al., 1998, 1994). Amygdala dysfunction has also been implicated in human disorders ranging from social anxiety (Birbaumer et al., 1998) to depression (Drevets, 2000) to autism (Bachevalier, 1994; Baron-Cohen et al., 2000; Bauman and Kemper, 1993). We produced selective amygdala lesions in 2-week-old macaque monkeys who were returned to their mothers for rearing. At 6-8 months of age, the lesioned animals demonstrated less fear of novel objects such as rubber snakes than age-matched controls. However, they displayed substantially more fear behavior than controls during dyadic social interactions. These results suggest that neonatal amygdala lesions dissociate a system that mediates social fear from one that mediates fear of inanimate objects. Furthermore, much of the age-appropriate repertoire of social behavior was present in amygdala-lesioned infants indicating that these lesions do not produce autistic-like behavior in monkeys. Finally, amygdala lesions early in development have different effects on social behavior than lesions produced in adulthood.

Aging↗

PubMed2001

Magnetic resonance imaging of the post-mortem autistic brain.

Magnetic resonance imaging (MRI) is a valuable, noninvasive tool for understanding structural abnormalities in the brain. The M.I.N.D. Institute at UC Davis has developed a protocol utilizing MRI to investigate anatomical differences in the post-mortem brain by applying a proton density weighted imaging sequence for optimal differences in image intensity (contrast) between gray and white matter. Images of the brain obtained prior to distribution of tissue and further neuropathological examination provide a record of how the brain appeared prior to tissue processing. The virtual representation of the whole brain can also be subjected to additional analyses, such as measuring the volume of brain regions or area of the cortical surface. We describe our procedures for carrying out post-mortem MRI of the human brain.

Autistic Disorder↗

PubMed2001

The effects of bilateral lesions of the amygdala on dyadic social interactions in rhesus monkeys (Macaca mulatta).

The role of the amygdala in dyadic social interactions of adult rhesus monkeys (Macaca mulatta) was assessed after bilateral ibotenic acid lesions. Social, nonsocial, and spatial behaviors of amygdalectomized and control monkeys were assessed in 3 dyadic experiments: constrained, unconstrained, and round robin. Lesions produced extensive bilateral damage to the amygdala. Across all experiments, the amygdalectomized monkeys demonstrated increased social affiliation, decreased anxiety, and increased confidence compared with control monkeys, particularly during early encounters. Normal subjects also demonstrated increased social affiliation toward the amygdalectomized subjects. These results indicate that amygdala lesions in adult monkeys lead to a decrease in the species-normal reluctance to immediately engage a novel conspecific in social behavior. The altered behavior of the amygdalectomized monkeys may have induced the increased social interactions from their normal companions. This is contrary to the idea that amygdalectomy produces a decrease in social interaction and increased aggression from conspecifics.

Aggression↗

PubMed2000

Macaque monkey retrosplenial cortex: I. three-dimensional and cytoarchitectonic organization.

This is the first in a series of reports on the neuroanatomic organization and connectivity of the macaque monkey retrosplenial cortex, i.e., areas 29 and 30. To elucidate the topographic configuration of the retrosplenial cortex and adjacent structures, we have made three-dimensional computer reconstructions of the posterior cingulate region that includes the retrosplenial cortex. The largest portion of the posterior cingulate gyrus is located dorsal to the corpus callosum. At the caudal limit of the corpus callosum, the gyrus curves around the splenium, turns laterally and forms a region called the isthmus that links the cingulate and parahippocampal gyri. The isthmus contains the caudomedial lobule, which is a rostrally oriented bulge that is made up, in part, of portions of the retrosplenial cortex. To delineate the subdivisions of the retrosplenial and adjacent cortices, we conducted a cytoarchitectonic analysis by using cerebral hemispheres that were cut at oblique angles and stained with a variety of techniques, including immunohistochemistry for nonphosphorylated neurofilament protein. The dorsal bank of the callosal sulcus and the rostral surface of the isthmus are covered by the retrosplenial cortical areas 29l, 29m, and 30, whereas most of the medial surface of the posterior cingulate gyrus and the ventral bank of the posterior cingulate sulcus consist of areas 23i and 23e. The most caudoventral portion of the cingulate gyrus is composed of an area (area 23v) that resembles the retrosplenial and posterior cingulate cortices but has a much more prominent layer IV. On the dorsal bank of the calcarine sulcus, we also defined a transitional zone, area 30v, located between the retrosplenial cortex and the prestriate visual cortex.

Animals↗

PubMed2000

A double labeling technique using WGA-apoHRP-gold as a retrograde tracer and non-isotopic in situ hybridization histochemistry for the detection of mRNA.

We describe a novel method to study the neurochemical nature of a specific neuronal pathway by using conjugated WGA-apoHRP as a retrograde tracer and non-isotopic in situ hybridization histochemistry to examine the expression of mRNA. The technique was developed to eliminate the reduction of retrograde tracer during the rigorous procedures involved in in situ hybridization. The tracer was injected stereotaxically into the brainstem of Macaca fascicularis monkeys. Sections through the central nucleus of the amygdala were processed for the visualization of the retrogradely transported WGA-apoHRP-gold using a silver enhanced reaction, followed by non radioactive in situ hybridization for the mRNA encoding glutamic acid decarboxylase (GAD67). Numerous retrogradely labeled cells were observed in the central nucleus of the amygdala. Comparison of double-labeled sections with sections processed for the retrograde tracer alone indicated that there was relatively little loss of the retrograde tracer during the in situ hybridization processing. This method provides a relatively simple and reliable tool to study the molecular phenotype of identified projection neurons.

Afferent Pathways↗

PubMed2000

Topographic organization of cortical inputs to the lateral nucleus of the macaque monkey amygdala: a retrograde tracing study.

The objective of this study was to identify cortical areas that project to the lateral nucleus of the macaque monkey amygdaloid complex. Discrete injections of the fluorescent retrograde tracers Fast blue and Diamidino yellow were placed into different locations within the lateral nucleus. Retrogradely labeled cells were mapped using a computer-aided digitizing system. In the frontal cortex, low numbers of retrogradely labeled cells were observed in medial and orbitofrontal regions (areas 10, 11, 12, 13, 13a, and 14). In the anterior cingulate cortex, low to moderate numbers of retrogradely labeled cells were located in areas 25, 24, and 32. In the insula, there were moderate to high numbers of retrogradely labeled cells in agranular and dysgranular regions. The parainsula cortex also demonstrated a moderate to high number of retrogradely labeled cells. In the temporal lobe, retrogradely labeled cells were most numerous in the rostral (polar) portion of the perirhinal cortex. Large numbers of labeled cells were also located throughout more caudal portions of the perirhinal regions as well as in the entorhinal cortex, area TE, and the superior temporal gyrus. Fewer retrogradely labeled cells were observed in the cortex along the dorsal bank of the superior temporal sulcus, in the parahippocampal cortex, and in area TEO. Although retrograde tracers can provide only limited evidence for topography, we nonetheless noted that the density of retrogradely labeled cells in a cortical area reliably depended on the location of the tracer injection in the lateral nucleus.

Amygdala↗

PubMed2000

Morphological and electrophysiological characteristics of layer V neurons of the rat medial entorhinal cortex.

This study aimed to characterize the morphological and electrophysiological properties of neurons in layer V of the entorhinal cortex in the rat brain. Using the in vitro slice preparation and sharp electrode techniques, we recorded from layer V neurons located in the medial entorhinal cortex. Recorded cells were also labeled with biocytin. Based on morphological criteria, layer V of the entorhinal cortex is comprised of three categories of neurons: pyramidal cells, horizontal cells, and polymorphic cells. Horizontal cells could be easily distinguished from the pyramidal cells because the bulk of their dendritic plexus extended horizontally within layer V. Polymorphic cells vary in size and shape. Interestingly, they typically do not have apical dendrites, and some of them have dendrites that extend into the subiculum. Based on electrophysiological criteria alone, it was not possible to unequivocally distinguish the morphological cell types because they were somewhat heterogeneous with respect to several parameters including inward rectification, spike-frequency adaptation, and intrinsic oscillations. Nevertheless, although most horizontal cells displayed time-dependent inward rectification, most pyramidal cells displayed fast inward rectification exclusively. None of the entorhinal cortex layer V cells displayed oscillatory activity like that of neocortical layer V "bursting" cells, although neurons from all groups displayed rhythmic subthreshold membrane potential oscillations. In summary, we have found that layer V of the rat medial entorhinal cortex consists of three morphologically distinct neuronal subtypes that cannot be clearly distinguished from each other by traditional electrophysiological measures.

Animals↗