RESUMO
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.
Assuntos
Tonsila do Cerebelo/patologia , Lesões Encefálicas/fisiopatologia , Vias Neurais/fisiologia , Tonsila do Cerebelo/diagnóstico por imagem , Animais , Animais Recém-Nascidos , Lesões Encefálicas/induzido quimicamente , Lesões Encefálicas/diagnóstico por imagem , Lesões Encefálicas/patologia , Conectoma , Imagem de Difusão por Ressonância Magnética , Agonistas de Aminoácidos Excitatórios/toxicidade , Feminino , Ácido Ibotênico/toxicidade , Processamento de Imagem Assistida por Computador , Estudos Longitudinais , Macaca mulatta , MasculinoRESUMO
Written and verbal languages are neurobehavioral traits vital to the development of communication skills. Unfortunately, disorders involving these traits-specifically reading disability (RD) and language impairment (LI)-are common and prevent affected individuals from developing adequate communication skills, leaving them at risk for adverse academic, socioeconomic and psychiatric outcomes. Both RD and LI are complex traits that frequently co-occur, leading us to hypothesize that these disorders share genetic etiologies. To test this, we performed a genome-wide association study on individuals affected with both RD and LI in the Avon Longitudinal Study of Parents and Children. The strongest associations were seen with markers in ZNF385D (OR = 1.81, P = 5.45 × 10(-7) ) and COL4A2 (OR = 1.71, P = 7.59 × 10(-7) ). Markers within NDST4 showed the strongest associations with LI individually (OR = 1.827, P = 1.40 × 10(-7) ). We replicated association of ZNF385D using receptive vocabulary measures in the Pediatric Imaging Neurocognitive Genetics study (P = 0.00245). We then used diffusion tensor imaging fiber tract volume data on 16 fiber tracts to examine the implications of replicated markers. ZNF385D was a predictor of overall fiber tract volumes in both hemispheres, as well as global brain volume. Here, we present evidence for ZNF385D as a candidate gene for RD and LI. The implication of transcription factor ZNF385D in RD and LI underscores the importance of transcriptional regulation in the development of higher order neurocognitive traits. Further study is necessary to discern target genes of ZNF385D and how it functions within neural development of fluent language.
Assuntos
Dislexia/genética , Estudo de Associação Genômica Ampla , Transtornos do Desenvolvimento da Linguagem/genética , Fatores de Transcrição/metabolismo , Estudos de Casos e Controles , Córtex Cerebral/fisiologia , Criança , Colágeno Tipo IV/genética , Feminino , Humanos , Estudos Longitudinais , Masculino , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , Sulfotransferases/genética , Fatores de Transcrição/química , Fatores de Transcrição/genética , Dedos de ZincoRESUMO
Antibodies directed against fetal brain proteins of 37 and 73 kDa molecular weight are found in approximately 12% of mothers who have children with autism spectrum disorder (ASD), but not in mothers of typically developing children. This finding has raised the possibility that these immunoglobulin G (IgG) class antibodies cross the placenta during pregnancy and impact brain development, leading to one form of ASD. We evaluated the pathogenic potential of these antibodies by using a nonhuman primate model. IgG was isolated from mothers of children with ASD (IgG-ASD) and of typically developing children (IgG-CON). The purified IgG was administered to two groups of female rhesus monkeys (IgG-ASD; n=8 and IgG-CON; n=8) during the first and second trimesters of pregnancy. Another control group of pregnant monkeys (n=8) was untreated. Brain and behavioral development of the offspring were assessed for 2 years. Behavioral differences were first detected when the macaque mothers responded to their IgG-ASD offspring with heightened protectiveness during early development. As they matured, IgG-ASD offspring consistently deviated from species-typical social norms by more frequently approaching familiar peers. The increased approach was not reciprocated and did not lead to sustained social interactions. Even more striking, IgG-ASD offspring displayed inappropriate approach behavior to unfamiliar peers, clearly deviating from normal macaque social behavior. Longitudinal magnetic resonance imaging analyses revealed that male IgG-ASD offspring had enlarged brain volume compared with controls. White matter volume increases appeared to be driving the brain differences in the IgG-ASD offspring and these differences were most pronounced in the frontal lobes.
Assuntos
Transtorno Autístico/imunologia , Autoanticorpos/imunologia , Encéfalo/crescimento & desenvolvimento , Comportamento Social , Fatores Etários , Animais , Encéfalo/imunologia , Feminino , Humanos , Macaca mulatta , Imageamento por Ressonância Magnética , Masculino , Troca Materno-Fetal/imunologia , Proteínas do Tecido Nervoso/imunologia , Neuroimagem , GravidezRESUMO
Although the orbitofrontal cortex has been implicated in important aspects of social behavior, few studies have evaluated semi-naturalistic social behavior in nonhuman primates after discrete lesions of this cortical area. In the present report, we evaluated the behavior of adult rhesus monkeys during dyadic social interactions with novel animals following discrete lesions of the orbitofrontal cortex. In a constrained condition, in which animals could engage in only restricted social behaviors, there were no significant differences in social behavior between the lesion group and the sham-operated control group. When the experimental animals could freely interact with partner animals, however, lesioned animals differed from control animals in terms of social interest and fear-related behaviors. These alterations were contingent on the partner with which they interacted. The lesioned animals, when compared to the control animals, had a significantly greater propensity to approach some but not all of their social partners. They also grimaced more towards the partner animal that they did not approach. Behavioral alterations were more apparent during the initial interactions between animals. We discuss these findings in relation to the role of the orbitofrontal cortex in context dependent modulation of social behavior.
Assuntos
Comportamento Animal/fisiologia , Lobo Frontal/fisiologia , Comportamento Social , Animais , Lobo Frontal/lesões , Macaca mulattaRESUMO
The amygdala is widely recognized to play a central role in emotional processing. In nonhuman primates, the amygdala appears to be critical for generating appropriate behavioral responses in emotionally salient contexts. One common finding is that macaque monkeys that receive amygdala lesions as adults are behaviorally uninhibited in the presence of potentially dangerous objects. While control animals avoid these objects, amygdala-lesioned animals readily interact with them. Despite a large literature documenting the role of the amygdala in emotional processing in adult rhesus macaques, little research has assessed the role of the amygdala across the macaque neurodevelopmental trajectory. We assessed the behavioral responses of 3-year-old (juvenile) rhesus macaques that received bilateral ibotenic acid lesions of the amygdala or hippocampus at 2 weeks of age. Animals were presented with salient objects known to produce robust fear-related responses in macaques (e.g., snakes and reptile-like objects), mammal-like objects that included animal-like features (e.g., eyes and mouths) but not reptile-like features (e.g., scales), and non-animal objects. The visual complexity of objects was scaled to vary the objects' salience. In contrast to control and hippocampus-lesioned animals, amygdala-lesioned animals were uninhibited in the presence of potentially dangerous objects. They readily retrieved food rewards placed near these objects and physically explored the objects. Furthermore, while control and hippocampus-lesioned animals differentiated between levels of object complexity, amygdala-lesioned animals did not. Taken together, these findings suggest that early damage to the amygdala, like damage sustained during adulthood, permanently compromises emotional processing.
Assuntos
Tonsila do Cerebelo/fisiologia , Medo/fisiologia , Inibição Psicológica , Animais , Animais Recém-Nascidos , Comportamento Animal/fisiologia , Hipocampo/fisiologia , Ácido Ibotênico/administração & dosagem , Macaca mulatta , Imageamento por Ressonância Magnética , Masculino , Microinjeções , Estimulação Luminosa/métodos , Recompensa , Percepção Visual/fisiologiaRESUMO
Previous research in our laboratory has shown that damage to the amygdala in neonatal rhesus monkeys profoundly alters behaviors associated with fear processing, while leaving many aspects of social development intact. Little is known, however, about the impact of neonatal lesions of the amygdala on later developing aspects of social behavior. A well-defined phenomenon in the development of young female rhesus monkeys is an intense interest in infants that is typically characterized by initiating proximity or attempting to hold them. The extent to which young females are interested in infants may have important consequences for the development of species-typical maternal behavior. Here we report the results of a study that was designed to assess interest in infants by female rhesus monkeys that received neonatal lesions to the amygdala, hippocampus or a sham surgical procedure. Subjects were first paired with pregnant "stimulus" females to assess social interactions with them prior to the birth of the infants. There were few behavioral differences between lesion groups when interacting with the pregnant females. However, following the birth of the infants, the amygdala-lesioned females showed significantly less interest in the infants than did control or hippocampus-lesioned females. They directed fewer affiliative vocalizations and facial expressions to the mother-infant pair compared to the hippocampus-lesioned and control females. These findings suggest that neonatal damage to the amygdala, but not the hippocampus, impairs important precursors of non-human primate maternal behavior.
Assuntos
Tonsila do Cerebelo/fisiologia , Hipocampo/fisiologia , Comportamento Materno/fisiologia , Comportamento Social , Animais , Animais Recém-Nascidos , Expressão Facial , Medo/fisiologia , Feminino , Macaca mulatta , Privação Materna , Gravidez , Vocalização AnimalRESUMO
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.
Assuntos
Tonsila do Cerebelo/lesões , Tonsila do Cerebelo/fisiologia , Hipocampo/lesões , Hipocampo/fisiologia , Comportamento Estereotipado/fisiologia , Fatores Etários , Análise de Variância , Animais , Animais Recém-Nascidos , Comportamento Animal , Peso Corporal , Feminino , Macaca mulatta , MasculinoRESUMO
Hippocampal formation plays a prominent role in episodic memory formation and consolidation. It is likely that episodic memory representations are constructed from cortical information that is mostly funnelled through the entorhinal cortex to the hippocampus. The entorhinal cortex returns processed information to the neocortex. Retrograde tracing studies have shown that neocortical afferents to the entorhinal cortex originate almost exclusively in polymodal association cortical areas. However, the use of retrograde studies does not address the question of the laminar and topographical distribution of cortical projections within the entorhinal cortex. We examined material from 60 Macaca fascicularis monkeys in which cortical deposits of either (3)H-amino acids or biotinylated dextran-amine as anterograde tracers were made into different cortical areas (the frontal, cingulate, temporal and parietal cortices). The various cortical inputs to the entorhinal cortex present a heterogeneous topographical distribution. Some projections terminate throughout the entorhinal cortex (afferents from medial area 13 and posterior parahippocampal cortex), while others have more limited termination, with emphasis either rostrally (lateral orbitofrontal cortex, agranular insular cortex, anterior cingulate cortex, perirhinal cortex, unimodal visual association cortex), intermediate (upper bank of the superior temporal sulcus, unimodal auditory association cortex) or caudally (parietal and retrosplenial cortices). Many of these inputs overlap, particularly within the rostrolateral portion of the entorhinal cortex. Some projections were directed mainly to superficial layers (I-III) while others were heavier to deep layers (V-VI) although areas of dense projections typically spanned all layers. A primary report will provide a detailed analysis of the regional and laminar organization of these projections. Here we provide a general overview of these projections in relation to the known neuroanatomy of the entorhinal cortex.
Assuntos
Córtex Entorrinal/anatomia & histologia , Macaca fascicularis/anatomia & histologia , Animais , Córtex Entorrinal/fisiologia , Hipocampo/anatomia & histologia , Hipocampo/fisiologia , Memória/fisiologia , Neocórtex/anatomia & histologia , Neocórtex/fisiologiaRESUMO
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.
Assuntos
Tonsila do Cerebelo/fisiologia , Face , Expressão Facial , Agressão/fisiologia , Tonsila do Cerebelo/citologia , Animais , Condicionamento Psicológico/fisiologia , Interpretação Estatística de Dados , Eletrodos , Eletrofisiologia , Fixação Ocular/fisiologia , Humanos , Macaca mulatta , Masculino , Neurônios/fisiologia , Estimulação Luminosa , Percepção Social , Percepção Visual/fisiologiaRESUMO
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.
Assuntos
Tonsila do Cerebelo/fisiologia , Hipocampo/fisiologia , Macaca mulatta/fisiologia , Macaca mulatta/psicologia , Predomínio Social , Agressão/fisiologia , Tonsila do Cerebelo/lesões , Animais , Animais Recém-Nascidos , Comportamento Animal , Agonistas de Aminoácidos Excitatórios/toxicidade , Medo/psicologia , Preferências Alimentares/psicologia , Hipocampo/lesões , Ácido Ibotênico/toxicidade , Imageamento por Ressonância Magnética/métodosRESUMO
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.
Assuntos
Eletrofisiologia , Hipocampo/citologia , Células Piramidais/anatomia & histologia , Células Piramidais/fisiologia , Animais , Tamanho Celular , Dendritos/metabolismo , Dendritos/ultraestrutura , Relação Dose-Resposta à Radiação , Estimulação Elétrica/métodos , Feminino , Imageamento Tridimensional/instrumentação , Técnicas In Vitro , Lisina/análogos & derivados , Lisina/metabolismo , Macaca/anatomia & histologia , Masculino , Potenciais da Membrana/fisiologia , Potenciais da Membrana/efeitos da radiação , Células Piramidais/ultraestrutura , Ratos , Coloração pela Prata/métodosRESUMO
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.
Assuntos
Tonsila do Cerebelo/metabolismo , Tonsila do Cerebelo/ultraestrutura , Fibras Nervosas/metabolismo , Fibras Nervosas/ultraestrutura , Serotonina/metabolismo , Animais , Soros Imunes , Imuno-Histoquímica , Macaca fascicularis , Masculino , Fotomicrografia , Serotonina/imunologia , Terminologia como Assunto , Distribuição TecidualRESUMO
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.
Assuntos
Tonsila do Cerebelo/fisiologia , Aprendizagem da Esquiva/fisiologia , Medo/fisiologia , Macaca mulatta/fisiologia , Macaca mulatta/psicologia , Comportamento Social , Animais , Animais Recém-Nascidos , Medo/psicologia , Hipocampo/fisiologia , Processos Mentais/fisiologia , Distribuição AleatóriaRESUMO
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.
Assuntos
Tonsila do Cerebelo/fisiologia , Macaca mulatta/fisiologia , Macaca mulatta/psicologia , Privação Materna , Comportamento Social , Fatores Etários , Tonsila do Cerebelo/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Comportamento Animal/fisiologia , Comportamento de Escolha/fisiologia , Medo/fisiologia , Feminino , Ácido Ibotênico/farmacologia , Masculino , Apego ao Objeto , Reconhecimento Psicológico/fisiologiaRESUMO
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.
Assuntos
Tonsila do Cerebelo/fisiopatologia , Transtorno Autístico/fisiopatologia , Dano Encefálico Crônico/fisiopatologia , Mapeamento Encefálico , Tonsila do Cerebelo/lesões , Animais , Transtorno Autístico/etiologia , Dano Encefálico Crônico/complicações , Modelos Animais de Doenças , Haplorrinos , HumanosRESUMO
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.
Assuntos
Anatomia/história , Giro Para-Hipocampal/anatomia & histologia , Lobo Temporal/anatomia & histologia , Terminologia como Assunto , Animais , Haplorrinos , História do Século XX , Humanos , Imuno-Histoquímica , Proteínas de Neurofilamentos/metabolismo , Giro Para-Hipocampal/metabolismo , Lobo Temporal/metabolismoRESUMO
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.
Assuntos
Tonsila do Cerebelo/anatomia & histologia , Vias Neurais/anatomia & histologia , Córtex Visual/anatomia & histologia , Amidinas/farmacocinética , Animais , Mapeamento Encefálico , Corantes Fluorescentes/farmacocinética , Macaca mulatta , Vias Neurais/metabolismo , Córtex Visual/metabolismoRESUMO
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.
Assuntos
Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/fisiologia , Canabinoides/farmacologia , Entorpecentes/farmacologia , Tonsila do Cerebelo/citologia , Analgésicos/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Benzoxazinas , Relação Dose-Resposta a Droga , Medo/efeitos dos fármacos , Medo/fisiologia , Ácido Ibotênico/administração & dosagem , Macaca mulatta , Imageamento por Ressonância Magnética , Masculino , Microinjeções , Morfina/farmacologia , Morfolinas/farmacologia , Naftalenos/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Medição da Dor/efeitos dos fármacos , Tempo de Reação/efeitos dos fármacos , VigíliaRESUMO
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.
Assuntos
Envelhecimento/fisiologia , Tonsila do Cerebelo/crescimento & desenvolvimento , Tonsila do Cerebelo/fisiologia , Medo/fisiologia , Macaca mulatta/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Comportamento Social , Tonsila do Cerebelo/lesões , Animais , Animais Recém-Nascidos , Comportamento Animal/fisiologia , Denervação , Comportamento Exploratório/fisiologia , Macaca mulatta/anatomia & histologia , Tempo de Reação/fisiologia , Transtornos do Comportamento Social/etiologia , Transtornos do Comportamento Social/patologia , Transtornos do Comportamento Social/fisiopatologiaRESUMO
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.