Distribution of vasoactive intestinal peptide (VIP) immunoreactivity in the rat pallial and subpallial amygdala and colocalization with γ-aminobutyric acid (GABA).

The amygdaloid complex, also known as the amygdala, is a heterogeneous group of distinct nuclear and cortical pallial and subpallial structures. The amygdala plays an important role in several complex functions including emotional behavior and learning. The expression of calcium-binding proteins and peptides in GABAergic neurons located in the pallial and subpallial amygdala is not uniform and is sometimes restricted to specific groups of cells. Vasoactive intestinal polypeptide (VIP) is present in specific subpopulations of GABAergic cells in the amygdala. VIP immunoreactivity has been observed in somatodendritic and axonal profiles of the rat basolateral and central amygdala. However, a comprehensive analysis of the distribution of VIP immunoreactivity in the various pallial and subpallial structures is currently lacking. The present study used immunohistochemical and morphometric techniques to analyze the distribution and the neuronal localization of VIP immunoreactivity in the rat pallial and subpallial amygdala. In the pallial amygdala, VIP-IR neurons are local inhibitory interneurons that presumably directly and indirectly regulate the activity of excitatory pyramidal neurons. In the subpallial amygdala, VIP immunoreactivity is expressed in several inhibitory cell types, presumably acting as projection or local interneurons. The distribution of VIP immunoreactivity is non-homogeneous throughout the different areas of the amygdaloid complex, suggesting a distinct influence of this neuropeptide on local neuronal circuits and, consequently, on the cognitive, emotional, behavioral and endocrine activities mediated by the amygdala.

The Subcortical-Allocortical- Neocortical continuum for the Emergence and Morphological Heterogeneity of Pyramidal Neurons in the Human Brain.

Human cortical and subcortical areas integrate emotion, memory, and cognition when interpreting various environmental stimuli for the elaboration of complex, evolved social behaviors. Pyramidal neurons occur in developed phylogenetic areas advancing along with the allocortex to represent 70-85% of the neocortical gray matter. Here, we illustrate and discuss morphological features of heterogeneous spiny pyramidal neurons emerging from specific amygdaloid nuclei, in CA3 and CA1 hippocampal regions, and in neocortical layers II/III and V of the anterolateral temporal lobe in humans. Three-dimensional images of Golgi-impregnated neurons were obtained using an algorithm for the visualization of the cell body, dendritic length, branching pattern, and pleomorphic dendritic spines, which are specialized plastic postsynaptic units for most excitatory inputs. We demonstrate the emergence and development of human pyramidal neurons in the cortical and basomedial (but not the medial, MeA) nuclei of the amygdala with cells showing a triangular cell body shape, basal branched dendrites, and a short apical shaft with proximal ramifications as "pyramidal-like" neurons. Basomedial neurons also have a long and distally ramified apical dendrite not oriented to the pial surface. These neurons are at the beginning of the allocortex and the limbic lobe. "Pyramidal-like" to "classic" pyramidal neurons with laminar organization advance from the CA3 to the CA1 hippocampal regions. These cells have basal and apical dendrites with specific receptive synaptic domains and several spines. Neocortical pyramidal neurons in layers II/III and V display heterogeneous dendritic branching patterns adapted to the space available and the afferent inputs of each brain area. Dendritic spines vary in their distribution, density, shapes, and sizes (classified as stubby/wide, thin, mushroom-like, ramified, transitional forms, "atypical" or complex forms, such as thorny excrescences in the MeA and CA3 hippocampal region). Spines were found isolated or intermingled, with evident particularities (e.g., an extraordinary density in long, deep CA1 pyramidal neurons), and some showing a spinule. We describe spiny pyramidal neurons considerably improving the connectional and processing complexity of the brain circuits. On the other hand, these cells have some vulnerabilities, as found in neurodegenerative Alzheimer's disease and in temporal lobe epilepsy.

Resilience, pain, and the brain: Relationships differ by sociodemographics.

Chronic musculoskeletal (MSK) pain is disabling to individuals and burdensome to society. A relationship between telomere length and resilience was reported in individuals with consideration for chronic pain intensity. While chronic pain associates with brain changes, little is known regarding the neurobiological interface of resilience. In a group of individuals with chronic MSK pain, we examined the relationships between a previously investigated resilience index, clinical pain and functioning measures, and pain-related brain structures, with consideration for sex and ethnicity/race. A cross-sectional analysis of 166 non-Hispanic Black and non-Hispanic White adults, 45-85 years of age with pain ≥ 1 body site (s) over the past 3 months was completed. Measures of clinical pain and functioning, biobehavioral and psychosocial resilience, and structural MRI were completed. Our findings indicate higher levels of resilience associate with lower levels of clinical pain and functional limitations. Significant associations between resilience, ethnicity/race, and/or sex, and pain-related brain gray matter structure were demonstrated in the right amygdaloid complex, bilateral thalamus, and postcentral gyrus. Our findings provide compelling evidence that in order to decipher the neurobiological code of chronic pain and related protective factors, it will be important to improve how chronic pain is phenotyped; to include an equal representation of females in studies including analyses stratifying by sex, and to consider other sociodemographic factors.

Distribution and morphology of calbindin neurons in the Amygdaloid Complex of the marmoset monkey (callithrix jacchus).

The location and distribution of the calcium-binding protein calbindin-D28k (CB) has been considered to be of great value as a neuronal marker for identifying distinct brain regions and discrete neuronal populations. In the amygdaloid complex (AC), the balance of excitatory and inhibitory inputs is controlled by CB immunoreactive interneurons. Alterations of inhibitory mechanisms in the AC may play a role in the emotional symptomatology of neurological diseases like Alzheimer's and psychiatric disorders like posttraumatic stress disorder. The present investigation examined the distribution and morphology of CB-containing neurons, neuropils and fibers in marmoset monkey ACs by using immunohistochemical and morphometrical methods. We recognized four types of CB cells in the AC: type 1 (multipolar), type 2 (spherical or bipolar), type 3 (pyramidal) and type 4 (halo cells), a cell type specific to the marmoset located in the basal and central nuclei. We detected CB cells in all nuclei and areas of the AC, where most of the cells were present in the deep nuclei (lateral, basal, accessory basal and paralaminar). In the superficial nuclei (the nucleus of the lateral olfactory tract, medial nucleus, periamygdaloid cortex and cortical nuclei), the CB cells were abundant in layers 2 and 3. The intercalated nuclei contained small densely packed cells. The CB neuropils were particularly dense in layer 1 of the superficial nuclei, in the deep nuclei and in the amygdalohippocampal area. Large CB immunoreactive neurons in the white matter and fibers with varicosities were found in the myelin tracts that surrounded the AC. These findings are the first step in determining whether some of these cells are specifically disrupted in pathological states.

Amygdaloid complex anatomopathological findings in animal models of status epilepticus.

Temporal lobe epileptic seizures are one of the most common and well-characterized types of epilepsies. The current knowledge on the pathology of temporal lobe epilepsy relies strongly on studies of epileptogenesis caused by experimentally induced status epilepticus (SE). Although several temporal lobe structures have been implicated in the epileptogenic process, the hippocampal formation is the temporal lobe structure studied in the greatest amount and detail. However, studies in human patients and animal models of temporal lobe epilepsy indicate that the amygdaloid complex can be also an important seizure generator, and several pathological processes have been shown in the amygdala during epileptogenesis. Therefore, in the present review, we systematically selected, organized, described, and analyzed the current knowledge on anatomopathological data associated with the amygdaloid complex during SE-induced epileptogenesis. Amygdaloid complex participation in the epileptogenic process is evidenced, among others, by alterations in energy metabolism, circulatory, and fluid regulation, neurotransmission, immediate early genes expression, tissue damage, cell suffering, inflammation, and neuroprotection. We conclude that major efforts should be made in order to include the amygdaloid complex as an important target area for evaluation in future research on SE-induced epileptogenesis. This article is part of the Special Issue "NEWroscience 2018".

Quantitative assessment of amygdala in Macaca fascicularis monkeys.

The amygdaloid complex (AC) is involved in very relevant cognitive and emotional pathways and exhibits changes in aging and in some neurological and psychiatric disorders. The quantitative estimators of AC could be useful to understand the impact of amygdaloid pathology in these processes, both globally and for each nucleus in particular, and their neurons. The present study analyzes morphometric and stereological estimators in the whole AC and its three main nuclei (lateral [La], basal [Ba], and accessory basal [AB]) in six Macaca fascicularis monkeys. All the brains were fixed and sectioned in the coronal plane; Nissl-stained sections were used for estimation of size and form parameters in both, the AC, and the La, Ba, and AB nuclei separately. The study includes stereological estimates of the volume and surface area of the AC; also, volume of the neurons in the amygdaloid nuclei was estimated using the point-sampled intercepts method. Our results show that the AB nucleus is smaller than both the La and Ba nuclei in both morphometric and stereological estimators. Brain hemispheric side had not significant influence on any of quantitative estimates. The neuron volume was higher in the AB nucleus relative to LA and Ba of the nuclei. These data describe some quantitative parameters of the amygdaloid complex and their main nuclei that could help us to detect small changes in neurodegenerative and other pathological processes.

Increases in dendritic spine density in BLA without metabolic changes in a rodent model of PTSD.

Imaging studies have shown abnormal amygdala function in patients with posttraumatic stress disorder (PTSD). In addition, alterations in synaptic plasticity have been associated with psychiatric disorders and previous reports have indicated alterations in the amygdala morphology, especially in basolateral (BLA) neurons, are associated with stress-related disorders. Since, some individuals exposed to a traumatic event develop PTSD, the goals of this study were to evaluate the early effects of PTSD on amygdala glucose metabolism and analyze the possible BLA dendritic spine plasticity in animals with different levels of behavioral response. We employed the inescapable footshock protocol as an experimental model of PTSD and the animals were classified according to the duration of their freezing behavior into distinct groups: "extreme behavioral response" (EBR) and "minimal behavioral response". We evaluated the amygdala glucose metabolism at baseline (before the stress protocol) and immediately after the situational reminder using the microPET and the radiopharmaceutical 18F-FDG. The BLA dendritic spines were analyzed according to their number, density, shape and morphometric parameters. Our results show the EBR animals exhibited longer freezing behavior and increased proximal dendritic spines density in the BLA neurons. Neither the amygdaloid glucose metabolism, the types of dendritic spines nor their morphometric parameters showed statistically significant differences. The extreme behavior response induced by this PTSD protocol produces an early increase in BLA spine density, which is unassociated with either additional changes in the shape of spines or metabolic changes in the whole amygdala of Wistar rats.

Regulation of adenosine A2A receptor gene expression in a model of binge eating in the amygdaloid complex of female rats.

BACKGROUND: Pharmacological treatment approaches for eating disorders, such as binge eating disorder and bulimia nervosa, are currently limited. METHODS AND AIMS: Using a well-characterized animal model of binge eating, we investigated the epigenetic regulation of the A2A Adenosine Receptor (A2AAR) and dopaminergic D2 receptor (D2R) genes. RESULTS: Gene expression analysis revealed a selective increase of both receptor mRNAs in the amygdaloid complex of stressed and restricted rats, which exhibited binge-like eating, when compared to non-stressed and non-restricted rats. Consistently, pyrosequencing analysis revealed a significant reduction of the percentage of DNA methylation but only at the A2AAR promoter region in rats showing binge-like behaviour compared to the control animals. Focusing thus on A2AAR agonist (VT 7) administration (which inhibited the episode of binge systemically at 0.1 mg/kg or intra-central amygdala (CeA) injection at 900 ng/side) induced a significant increase of A2AAR mRNA levels in restricted and stressed rats when compared to the control group. In addition, we observed a significant decrease in A2AAR mRNA levels in rats treated with the A2AAR antagonist (ANR 94) at 1 mg/kg. Consistent changes in the DNA methylation status of the A2AAR promoter were found in restricted and stressed rats after administration of VT 7 or ANR 94. CONCLUSION: We confirm the role of A2AAR in binge eating behaviours, and we underline the importance of epigenetic regulation of the A2AAR gene, possibly due to a compensatory mechanism to counteract the effect of binge eating. We suggest that A2AAR activation, inducing receptor gene up-regulation, could be relevant to reduction of food consumption.

Amygdala growth from youth to adulthood in the macaque monkey.

Emerging evidence suggests that the human amygdala undergoes extensive growth through adolescence, coinciding with the acquisition of complex socioemotional learning. Our objective was to longitudinally map volumetric growth of the nonhuman primate amygdala in a controlled, naturalistic social environment from birth to adulthood. Magnetic resonance images were collected at five time-points in 24 male and female rhesus macaques from 6 months to adulthood at 5 years. We then compared amygdala growth to other brain regions, including newly collected isocortical gray and white matter volumes, and previously published data on the same cohort. We found that amygdala volume increases by nearly 50% from age 6 months to 5 years. This dramatic growth is in contrast to overall brain and hippocampal volume, which peak near 3 years, white matter, which slows from 3 to 5 years, and isocortical gray, which has a net decrease. Similar to isocortical gray and hippocampal volumes, amygdala volume is ~8% larger in males than females. Rate of growth does not differ by sex. Although the underlying neurobiological substrate for protracted amygdala growth into adulthood is unclear, we propose it may be due in part to the unique cellular development of immature neurons in paralaminar nucleus that mature in size and connectivity with age. Prolonged amygdala maturation raises the possibility that environmental and genetic perturbations that disrupt this trajectory may contribute to the emergence of psychiatric disorders, such as anxiety, depression, schizophrenia, and autism; all in which the amygdala is strongly implicated.

Cyto- and Myelo-Architecture of the Amygdaloid Complex of the Common Marmoset Monkey (Callithrix jacchus).

The amygdaloid complex (AC) is a heterogeneous aggregate of nuclei located in the rostromedial region of the temporal lobe. In addition to being partly connected among themselves, the AC nuclei are strongly interconnected with the cerebral cortex, striatum, basal forebrain, hypothalamus and brainstem. Animal and human functional studies have established that the AC is a central hub of the neuronal networks supporting emotional responsivity, particularly its negative/aversive components. Dysfunction of AC circuits in humans has been implicated in anxiety, depression, schizophrenia and bipolar disorder. The small New-World marmoset monkey (Callithrix jacchus) has recently become a key model for neuroscience research. However, the nuclear and fiber tract organization of marmoset AC has not been examined in detail. Thus, the extent to which it can be compared to the AC of Old-World (human and macaque) primates is yet unclear. Here, using Nissl and acetylcholinesterase (AChE) histochemical stains as a reference, we analyzed the cytoarchitecture and nuclear parcellation of the marmoset AC. In addition, given the increasing relevance of tractographic localization for high-resolution in vivo imaging studies in non-human primates, we also identified the myelin fiber tracts present within and around the AC as revealed by the Gallyas method. The present study provides a detailed atlas of marmoset AC. Moreover, it reveals that, despite phylogenetic distance and brain size differences, every nucleus and myelinated axon bundle described in human and macaque studies can be confidently recognized in marmosets.

Distribution of Calretinin Immunoreactivity in the Lateral Nucleus of the Bottlenose Dolphin (Tursiops truncatus) Amygdala.

The amgdaloid complex consists of different nuclei, each with unique cytoarchitectonic, chemoarchitectonic and connectional characteristics. Most of the inputs coming from cortical and subcortical areas enter the amygdala via the lateral nucleus, which makes it the main receiving structure of the complex. The activity of its neurons is coordinated and modulated by different inhibitory, GABAergic-interneurons, which can be classified for their expression of various calcium-binding proteins, as well as by morphological characteristics. This research based on the analysis of the amygdala of three bottlenose dolphins, provides the first description of the topography, cytoarchitecture and distribution of calretinin immunoreactivity of the lateral nucleus. Our observations on the bottlenose dolphin confirmed the general topography of the mammalian amygdala and of the lateral nucleus. Notably, we identified six subdivision of the nucleus, more than those reported until now in the rat, monkey and human lateral nucleus. This could reveal an outstanding capability of integration and elaboration of external stimuli. In addition, we observed a strong presence of CR-immunoreactive (-ir) neurons and fibres. CR-ir neurons were mainly non-pyramidal inhibitory neurons; in particular, 80% of IR-cells were represented by large and small polygonal neurons. In the lateral nucleus of the human amygdala, CR-ir neurons form inhibitory synapses on calbindin-D28k-IR inhibitory interneurons. Since calbindin-D28k-ir interneurons make inhibitory synapses on the pyramidal cells, the final goal of the CR-ir interneurons could be the synchronization of cells activity, thus playing an important role in the control of information flow in the lateral amygdalar nucleus. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 300:2008-2016, 2017. © 2017 Wiley Periodicals, Inc.

Structural Organization of Cerebral Basolateral Nucleus of the Amygdaloid Complex in WAG-Rij Rats with Different Genotypes by the TAQ 1A Locus of Dopamine 2 Receptor Gene (DRD2).

Anxiety levels and structural organization of the basolateral nucleus of the amygdaloid complex were analyzed in WAG/Rij rats with genotypes A1/A1 and A2/A2 by DRD2 locus Taq 1A. Association of anxious behavior with A2/A2 genotype and the relationship between the structural organization of the nucleus and polymorphic variants of this locus are detected.

Potential of zebrafish as a model for exploring the role of the amygdala in emotional memory and motivational behavior.

Emotion is a key aspect of behavior, enabling humans and animals to assign either positive or negative values to sensory inputs and thereby to make appropriate decisions. Classical experiments in mammalian models, mainly in primates and rodents, have shown that the amygdala is essential for appetitive and aversive associative processing and that dysfunction of this brain region leads to various psychiatric conditions, including depression, generalized anxiety disorder, panic disorder, phobias, autism, and posttraumatic stress disorder. In the past 2 decades, the zebrafish (Danio rerio; Cyprinidae) has emerged as a versatile, reliable vertebrate model organism for the in vivo study of development, gene function, and numerous aspects of human pathologies. Small size, high fecundity, rapid external development, transparency, genetic tractability, and high genetic and physiologic homology with humans are among the factors that have contributed to the success with this small fish in different biomedical research areas. Recent findings indicate that, despite the anatomical differences in the brain structure of teleosts and tetrapods, fish possess a structure homologous to the mammalian amygdala, a hypothesis that is supported by the expression of molecular markers, analyses of neuronal projections in different brain areas, and behavioral studies. This Review summarizes this evidence and highlights a number of relevant bioassays in zebrafish to study emotional memory and motivational behavior.

Triggering Different Brain States Using Asynchronous Serial Communication to the Rat Amygdala.

Inputting information to the brain through direct electrical microstimulation must consider how underlying neural networks encode information. One unexplored possibility is that a single electrode delivering temporally coded stimuli, mimicking an asynchronous serial communication port to the brain, can trigger the emergence of different brain states. This work used a discriminative fear-conditioning paradigm in rodents in which 2 temporally coded microstimulation patterns were targeted at the amygdaloid complex. Each stimulus was a binary-coded "word" made up of 10 ms bins, with 1's representing a single pulse stimulus: A-1001111001 and B-1110000111. During 3 consecutive retention tests (i.e., day-word: 1-B; 2-A, and 3-B), only binary-coded words previously paired with a foot-electroshock elicited proper aversive behavior. To determine the neural substrates recruited by the different stimulation patterns, c-Fos expression was evaluated 90 min after the last retention test. Animals conditioned to word-B, after stimulation with word-B, demonstrated increased hypothalamic c-Fos staining. Animals conditioned to word-A, however, showed increased prefrontal c-Fos labeling. In addition, prefrontal-cortex and hypothalamic c-Fos staining for, respectively, word-B- and word-A-conditioned animals, was not different than that of an unpaired control group. Our results suggest that, depending on the valence acquired from previous learning, temporally coded microstimulation activates distinct neural networks and associated behavior.

D-Cycloserine acts via increasing the GluN1 protein expressions in the frontal cortex and decreases the avoidance and risk assessment behaviors in a rat traumatic stress model.

D-cycloserine (DCS), an FDA approved anti-tuberculosis drug has extensively been studied for its cognitive enhancer effects in psychiatric disorders. DCS may enhance the effects of fear extinction trainings in animals during exposure therapy and hence we investigated the effects of DCS on distinct behavioral parameters in a predator odor stress model and tested the optimal duration for repeated daily administrations of the agent. Cat fur odor blocks were used to produce stress and avoidance and risk assessment behavioral parameters were used where DCS or saline were used as treatments in adjunct to extinction trainings. We observed that DCS facilitated extinction training by providing further extinction of avoidance responses, risk assessment behaviors and increased the contact with the cue in a setting where DCS was administered before extinction trainings for 3 days without producing a significant tolerance. In amygdala and hippocampus, GluN1 protein expressions decreased 72h after the fear conditioning in the traumatic stress group suggesting a possible down-regulation of NMDARs. We observed that extinction learning increased GluN1 proteins both in the amygdaloid complex and the dorsal hippocampus of the rats receiving extinction training or extinction training with DCS. Our findings also indicate that DCS with extinction training increased GluN1 protein levels in the frontal cortex. We may suggest that action of DCS relies on enhancement of the consolidation of fear extinction in the frontal cortex.

Neuronal localization of the 5-HT2 receptor family in the amygdaloid complex.

The amygdaloid complex (or amygdala), a heterogeneous structure located in the medial portion of the temporal lobe, is composed of deep, superficial, and "remaining" nuclei. This structure is involved in the generation of emotional behavior, in the formation of emotional memories and in the modulation of the consolidation of explicit memories for emotionally arousing events. The serotoninergic fibers originating in the dorsal and medial raphe nuclei are critically involved in amygdalar functions. Serotonin (5-hydroxytryptamine, 5-HT) regulates amygdalar activity through the activation of the 5-HT2 receptor family, which includes three receptor subtypes: 5-HT2A, 5-HT2B, and 5-HT2C. The distribution and the functional activity of the 5-HT2 receptor family has been studied more extensively than that of the 5-HT2A receptor subtypes, especially in the deep nuclei. In these nuclei, the 5-HT2A receptor is expressed on both pyramidal and non-pyramidal neurons, and could play a critical role in the formation of emotional memories. However, the exact role of the 5-HT2A receptor subtypes, as well as that of the 5-HT2B and 5-HT2C receptor subtypes, in the modulation of the amygdalar microcircuits requires additional study. The present review reports data concerning the distribution and the functional roles of the 5-HT2 receptor family in the amygdala.

Increased nitric oxide-mediated neurotransmission in the medial prefrontal cortex is associated with the long lasting anxiogenic-like effect of predator exposure.

Posttraumatic stress disorder (PTSD) is an anxiety disorder caused by the experience of a severe traumatic event. In rats this disorder has been modeled by exposure to a predator threat. PTSD has been associated to structural and functional changes in the medial prefrontal cortex (mPFC). Direct injections into this brain region of glutamate antagonists or inhibitors of the nitric oxide synthase (NOS) enzyme cause anxiolytic-like effects in rodents. In the present work we investigated if the behavioral changes induced by predator exposure are associated with changes in the mPFC nitrergic system. Since the hippocampus, amygdala and dorsal periaqueductal grey have also been associated to anxiety disorders, including PTSD, we also verified if this procedure would modify the nitrergic system in these regions. Male Wistar rats were exposed to a dummy or live cat for ten minutes and tested in the elevated plus maze test (EPM) seven days later. Immediately after the test their brains were removed for neuronal NOS (nNOS) immunohistochemistry detection and measurements of nitrite/nitrate (NOx) levels. Exposure to the live cat increased freezing responses. One week later the animals that froze when confronted with the cat presented a decreased percentage of entries in the open arms of the EPM and an increased number of nNOS positive neurons in the mPFC and basolateral nucleus of amygdala, but not in the hippocampus, central and medial nuclei of amygdaloid complex or dorsal-lateral periaqueductal grey. Moreover, cat exposed animals showed increased NOx levels in the mPFC but not in the hippocampus one week later. The number of nNOS neurons and NOx levels in the mPFC showed a significant correlation with freezing time during cat exposure. Our results suggest that plastic modifications of the nitrergic system in the mPFC could be related to long lasting behavioral changes induced by severe traumatic events such as predator exposure.

Memory for fearful faces across development: specialization of amygdala nuclei and medial temporal lobe structures.

Enhanced memory for emotional faces is a significant component of adaptive social interactions, but little is known on its neural developmental correlates. We explored the role of amygdaloid complex (AC) and medial temporal lobe (MTL) in emotional memory recognition across development, by comparing fMRI activations of successful memory encoding of fearful and neutral faces in children (n = 12; 8-12 years) and adolescents (n = 12; 13-17 years). Memory for fearful faces was enhanced compared with neutral ones in adolescents, as opposed to children. In adolescents, activations associated with successful encoding of fearful faces were centered on baso-lateral AC nuclei, hippocampus, enthorhinal and parahippocampal cortices. In children, successful encoding of fearful faces relied on activations of centro-mesial AC nuclei, which was not accompanied by functional activation of MTL memory structures. Successful encoding of neutral faces depended on activations in anterior MTL region (hippocampal head and body) in adolescents, but more posterior ones (hippocampal tail and parahippocampal cortex) in children. In conclusion, two distinct functional specializations emerge from childhood to adolescence and result in the enhancement of memory for these particular stimuli: the specialization of baso-lateral AC nuclei, which is associated with the expertise in processing emotional facial expression, and which is intimately related to the specialization of MTL memory network. How the interplay between specialization of AC nuclei and of MTL memory structures is fundamental for the edification of social interactions remains to be elucidated.