RESUMEN
An obvious consequence of the coronavirus disease (COVID-19) pandemic is the worldwide reduction in social interaction, which is associated with many adverse effects on health in humans from babies to adults. Although social development under normal or isolated environments has been studied since the 1940s, the mechanism underlying social isolation (SI)-induced brain dysfunction remains poorly understood, possibly due to the complexity of SI in humans and translational gaps in findings from animal models. Herein, we present a systematic review that focused on brain changes at the molecular, cellular, structural and functional levels induced by SI at different ages and in different animal models. SI studies in humans and animal models revealed common socioemotional and cognitive deficits caused by SI in early life and an increased occurrence of depression and anxiety induced by SI during later stages of life. Altered neurotransmission and neural circuitry as well as abnormal development and function of glial cells in specific brain regions may contribute to the abnormal emotions and behaviors induced by SI. We highlight distinct alterations in oligodendrocyte progenitor cell differentiation and oligodendrocyte maturation caused by SI in early life and later stages of life, respectively, which may affect neural circuit formation and function and result in diverse brain dysfunctions. To further bridge animal and human SI studies, we propose alternative animal models with brain structures and complex social behaviors similar to those of humans.
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COVID-19 , Control de Infecciones , Pandemias , Aislamiento Social , Animales , Humanos , Conducta Animal , Encéfalo , EmocionesRESUMEN
Recent neuroimaging studies in humans have reported distinct temporal dynamics of gyri and sulci, which may be associated with putative functions of cortical gyrification. However, the complex folding patterns of the human cortex make it difficult to explain temporal patterns of gyrification. In this study, we used the common marmoset as a simplified model to examine the temporal characteristics and compare them with the complex gyrification of humans. Using a brain-inspired deep neural network, we obtained reliable temporal-frequency fingerprints of gyri and sulci from the awake rs-fMRI data of marmosets and humans. Notably, the temporal fingerprints of one region successfully classified the gyrus/sulcus of another region in both marmosets and humans. Additionally, the temporal-frequency fingerprints were remarkably similar in both species. We then analyzed the resulting fingerprints in several domains and adopted the Wavelet Transform Coherence approach to characterize the gyro-sulcal coupling patterns. In both humans and marmosets, sulci exhibited higher frequency bands than gyri, and the two were temporally coupled within the same range of phase angles. This study supports the notion that gyri and sulci possess unique and evolutionarily conserved features that are consistent across functional areas, and advances our understanding of the functional role of cortical gyrification.
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Callithrix , Corteza Cerebral , Animales , Humanos , Corteza Cerebral/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Neuroimagen , Redes Neurales de la ComputaciónRESUMEN
The corpus callosum (CC) is the largest white matter structure and the primary pathway for interhemispheric brain communication. Investigating callosal connectivity is crucial to unraveling the brain's anatomical and functional organization in health and disease. Classical anatomical studies have characterized the bulk of callosal axonal fibers as connecting primarily homotopic cortical areas. Whenever detected, heterotopic callosal fibers were ascribed to altered sprouting and pruning mechanisms in neurodevelopmental diseases such as CC dysgenesis (CCD). We hypothesized that these heterotopic connections had been grossly underestimated due to their complex nature and methodological limitations. We used the Allen Mouse Brain Connectivity Atlas and high-resolution diffusion-weighted imaging to identify and quantify homotopic and heterotopic callosal connections in mice, marmosets, and humans. In all 3 species, we show that ~75% of interhemispheric callosal connections are heterotopic and comprise the central core of the CC, whereas the homotopic fibers lay along its periphery. We also demonstrate that heterotopic connections have an essential role in determining the global properties of brain networks. These findings reshape our view of the corpus callosum's role as the primary hub for interhemispheric brain communication, directly impacting multiple neuroscience fields investigating cortical connectivity, neurodevelopment, and neurodevelopmental disorders.
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Encéfalo , Cuerpo Calloso , Humanos , Ratones , Animales , Vías Nerviosas/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Cuerpo Calloso/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética/métodos , Agenesia del Cuerpo Calloso/diagnóstico por imagen , Mamíferos , CallithrixRESUMEN
Recently, the functional roles of the human cortical folding patterns have attracted increasing interest in the neuroimaging community. However, most existing studies have focused on the gyro-sulcal functional relationship on a whole-brain scale but possibly overlooked the localized and subtle functional differences of brain networks. Actually, accumulating evidences suggest that functional brain networks are the basic unit to realize the brain function; thus, the functional relationships between gyri and sulci still need to be further explored within different functional brain networks. Inspired by these evidences, we proposed a novel intrinsic connectivity network (ICN)-guided pooling-trimmed convolutional neural network (I-ptFCN) to revisit the functional difference between gyri and sulci. By testing the proposed model on the task functional magnetic resonance imaging (fMRI) datasets of the Human Connectome Project, we found that the classification accuracy of gyral and sulcal fMRI signals varied significantly for different ICNs, indicating functional heterogeneity of cortical folding patterns in different brain networks. The heterogeneity may be contributed by sulci, as only sulcal signals show heterogeneous frequency features across different ICNs, whereas the frequency features of gyri are homogeneous. These results offer novel insights into the functional difference between gyri and sulci and enlighten the functional roles of cortical folding patterns.
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Corteza Cerebral , Conectoma , Humanos , Corteza Cerebral/diagnóstico por imagen , Conectoma/métodos , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Redes Neurales de la ComputaciónRESUMEN
The common marmoset (Callithrix jacchus) is quickly gaining traction as a premier neuroscientific model. However, considerable progress is still needed in understanding the functional and structural organization of the marmoset brain to rival that documented in longstanding preclinical model species, like mice, rats, and Old World primates. To accelerate such progress, we present the Marmoset Functional Brain Connectivity Resource (marmosetbrainconnectome.org), currently consisting of over 70 h of resting-state fMRI (RS-fMRI) data acquired at 500 µm isotropic resolution from 31 fully awake marmosets in a common stereotactic space. Three-dimensional functional connectivity (FC) maps for every cortical and subcortical gray matter voxel are stored online. Users can instantaneously view, manipulate, and download any whole-brain functional connectivity (FC) topology (at the subject- or group-level) along with the raw datasets and preprocessing code. Importantly, researchers can use this resource to test hypotheses about FC directly - with no additional analyses required - yielding whole-brain correlations for any gray matter voxel on demand. We demonstrate the resource's utility for presurgical planning and comparison with tracer-based neuronal connectivity as proof of concept. Complementing existing structural connectivity resources for the marmoset brain, the Marmoset Functional Brain Connectivity Resource affords users the distinct advantage of exploring the connectivity of any voxel in the marmoset brain, not limited to injection sites nor constrained by regional atlases. With the entire raw database (RS-fMRI and structural images) and preprocessing code openly available for download and use, we expect this resource to be broadly valuable to test novel hypotheses about the functional organization of the marmoset brain.
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Callithrix , Vigilia , Acceso a la Información , Animales , Encéfalo/fisiología , Callithrix/fisiología , Humanos , Imagen por Resonancia Magnética/métodos , Ratones , RatasRESUMEN
Curiosity is a fundamental nature of animals for adapting to changing environments, but its underlying brain circuits and mechanisms remain poorly understood. One main barrier is that existing studies use rewards to train animals and motivate their engagement in behavioral tasks. As such, the rewards become significant confounders in interpreting curiosity. Here, we overcame this problem by studying research-naïve and naturally curious marmosets that can proactively and persistently participate in a visual choice task without external rewards. When performing the task, the marmosets manifested a strong innate preference towards acquiring new information, associated with faster behavioral responses. Longitudinally functional magnetic resonance imaging revealed behavior-relevant brain states that reflected choice preferences and engaged several brain regions, including the cerebellum, the hippocampus, and cortical areas 19DI, 25, and 46D, with the cerebellum being the most prominent. These results unveil the essential brain circuits and dynamics underlying curiosity-driven activity.
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Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Conducta Exploratoria/fisiología , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiología , Animales , Callithrix , Conducta de Elección/fisiología , Femenino , Imagen por Resonancia Magnética/métodos , Masculino , Motivación/fisiologíaRESUMEN
The corpus callosum (CC), the anterior (AC), and the posterior (PC) commissures are the principal axonal fiber bundle pathways that allow bidirectional communication between the brain hemispheres. Here, we used the Allen mouse brain connectivity atlas and high-resolution diffusion-weighted MRI (DWI) to investigate interhemispheric fiber bundles in C57bl6/J mice, the most commonly used wild-type mouse model in biomedical research. We identified 1) commissural projections from the primary motor area through the AC to the contralateral hemisphere; and 2) intrathalamic interhemispheric fiber bundles from multiple regions in the frontal cortex to the contralateral thalamus. This is the first description of direct interhemispheric corticothalamic connectivity from the orbital cortex. We named these newly identified crossing points thalamic commissures. We also analyzed interhemispheric connectivity in the Balb/c mouse model of dysgenesis of the corpus callosum (CCD). Relative to C57bl6/J, Balb/c presented an atypical and smaller AC and weaker interhemispheric corticothalamic communication. These results redefine our understanding of interhemispheric brain communication. Specifically, they establish the thalamus as a regular hub for interhemispheric connectivity and encourage us to reinterpret brain plasticity in CCD as an altered balance between axonal reinforcement and pruning.
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Corteza Cerebral/fisiología , Vías Nerviosas/fisiología , Tálamo/fisiología , Sustancia Blanca/fisiología , Animales , Atlas como Asunto , Axones/fisiología , Imagen de Difusión por Resonancia Magnética , Lateralidad Funcional/fisiología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Corteza Motora/fisiología , Plasticidad Neuronal/fisiologíaRESUMEN
The standard anatomical brain template provides a common space and coordinate system for visualizing and analyzing neuroimaging data from large cohorts of subjects. Previous templates and atlases for the common marmoset brain were either based on data from a single individual or lacked essential functionalities for neuroimaging analysis. Here, we present new population-based in-vivo standard templates and tools derived from multi-modal data of 27 marmosets, including multiple types of T1w and T2w contrast images, DTI contrasts, and large field-of-view MRI and CT images. We performed multi-atlas labeling of anatomical structures on the new templates and constructed highly accurate tissue-type segmentation maps to facilitate volumetric studies. We built fully featured brain surfaces and cortical flat maps to facilitate 3D visualization and surface-based analyses, which are compatible with most surface analyzing tools, including FreeSurfer, AFNI/SUMA, and the Connectome Workbench. Analysis of the MRI and CT datasets revealed significant variations in brain shapes, sizes, and regional volumes of brain structures, highlighting substantial individual variabilities in the marmoset population. Thus, our population-based template and associated tools provide a versatile analysis platform and standard coordinate system for a wide range of MRI and connectome studies of common marmosets. These new template tools comprise version 3 of our Marmoset Brain Mapping Project and are publicly available via marmosetbrainmapping.org/v3.html.
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Atlas como Asunto , Mapeo Encefálico/métodos , Encéfalo/anatomía & histología , Callithrix/anatomía & histología , Animales , Femenino , Masculino , Estándares de ReferenciaRESUMEN
The rapid adoption of marmosets in neuroscience has created a demand for three dimensional (3D) atlases of the brain of this species to facilitate data integration in a common reference space. We report on a new open access template of the marmoset cortex (the Nencki-Monash, or NM template), representing a morphological average of 20 brains of young adult individuals, obtained by 3D reconstructions generated from Nissl-stained serial sections. The method used to generate the template takes into account morphological features of the individual brains, as well as the borders of clearly defined cytoarchitectural areas. This has resulted in a resource which allows direct estimates of the most likely coordinates of each cortical area, as well as quantification of the margins of error involved in assigning voxels to areas, and preserves quantitative information about the laminar structure of the cortex. We provide spatial transformations between the NM and other available marmoset brain templates, thus enabling integration with magnetic resonance imaging (MRI) and tracer-based connectivity data. The NM template combines some of the main advantages of histology-based atlases (e.g. information about the cytoarchitectural structure) with features more commonly associated with MRI-based templates (isotropic nature of the dataset, and probabilistic analyses). The underlying workflow may be found useful in the future development of 3D brain atlases that incorporate information about the variability of areas in species for which it may be impractical to ensure homogeneity of the sample in terms of age, sex and genetic background.
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Atlas como Asunto , Callithrix/anatomía & histología , Corteza Cerebral/anatomía & histología , Animales , Femenino , Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética/métodos , MasculinoRESUMEN
Neuroimaging non-human primates (NHPs) is a growing, yet highly specialized field of neuroscience. Resources that were primarily developed for human neuroimaging often need to be significantly adapted for use with NHPs or other animals, which has led to an abundance of custom, in-house solutions. In recent years, the global NHP neuroimaging community has made significant efforts to transform the field towards more open and collaborative practices. Here we present the PRIMatE Resource Exchange (PRIME-RE), a new collaborative online platform for NHP neuroimaging. PRIME-RE is a dynamic community-driven hub for the exchange of practical knowledge, specialized analytical tools, and open data repositories, specifically related to NHP neuroimaging. PRIME-RE caters to both researchers and developers who are either new to the field, looking to stay abreast of the latest developments, or seeking to collaboratively advance the field .
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Acceso a la Información , Neuroimagen/métodos , Sistemas en Línea , Primates/anatomía & histología , Primates/fisiología , AnimalesRESUMEN
Corpus callosum dysgenesis (CCD) is a developmental brain condition in which some white matter fibers fail to find their natural course across the midplane, reorganizing instead to form new aberrant pathways. This type of white matter reorganization is known as long-distance plasticity (LDP). The present work aimed to characterize the Balb/c mouse strain as a model of CCD. We employed high-resolution anatomical MRI in 81 Balb/c and 27 C57bl6 mice to show that the Balb/c mouse strain presents a variance in the size of the CC that is 3.9 times higher than the variance of normotypical C57bl6. We also performed high-resolution diffusion-weighted imaging (DWI) in 8 Balb/c and found that the Balb/c strain shows aberrant white matter bundles, such as the Probst (5/8 animals) and the Sigmoid bundles (7/8 animals), which are similar to those found in humans with CCD. Using a histological tracer technique, we confirmed the existence of these aberrant bundles in the Balb/c strain. Interestingly, we also identified sigmoid-like fibers in the C57bl6 strain, thought to a lesser degree. Next, we used a connectome approach and found widespread brain connectivity differences between Balb/c and C57bl6 strains. The Balb/c strain also exhibited increased variability of global connectivity. These findings suggest that the Balb/c strain presents local and global changes in brain structural connectivity. This strain often presents with callosal abnormalities, along with the Probst and the Sigmoid bundles, making it is an attractive animal model for CCD and LDP in general. Our results also show that even the C57bl6 strain, which typically serves as a normotypical control animal in a myriad of studies, presents sigmoid-fashion pattern fibers laid out in the brain. These results suggest that these aberrant fiber pathways may not necessarily be a pathological hallmark, but instead an alternative roadmap for misguided axons. Such findings offer new insights for interpreting the significance of CCD-associated LDP in humans.
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Agenesia del Cuerpo Calloso/diagnóstico por imagen , Agenesia del Cuerpo Calloso/fisiopatología , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Animales , Conectoma , Cuerpo Calloso/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética , Femenino , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Fibras Nerviosas Mielínicas/patología , Especificidad de la Especie , Sustancia Blanca/diagnóstico por imagenRESUMEN
Right hemispheric dominance in tonal bilingualism is still controversial. In this study, we investigated hemispheric dominance in 30 simultaneous Bai-Mandarin tonal bilinguals and 28 Mandarin monolinguals using multimodal neuroimaging. Resting-state functional connectivity (RSFC) analysis was first performed to reveal the changes of functional connections within the language-related network. Voxel-based morphology (VBM) and tract-based spatial statistics (TBSS) analyses were then used to identify bilinguals' alterations in gray matter volume (GMV) and fractional anisotropy (FA) of white matter, respectively. RSFC analyses revealed significantly increased functional connections of the right pars-orbital part of the inferior frontal gyrus (IFG) with right caudate, right pars-opercular part of IFG, and left inferior temporal gyrus in Bai-Mandarin bilinguals compared to monolinguals. VBM and TBSS analyses further identified significantly greater GMV in right pars-triangular IFG and increased FA in right superior longitudinal fasciculus (SLF) in bilinguals than in monolinguals. Taken together, these results demonstrate the integrative role of the right IFG in tonal language processing of bilinguals. Our findings suggest that the intrinsic language network in simultaneous tonal bilinguals differs from that of monolinguals in terms of both function and structure.
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Conectoma , Dominancia Cerebral/fisiología , Sustancia Gris , Multilingüismo , Red Nerviosa , Corteza Prefrontal , Sustancia Blanca , Adulto , China , Imagen de Difusión Tensora , Femenino , Sustancia Gris/anatomía & histología , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/fisiología , Humanos , Imagen por Resonancia Magnética , Masculino , Red Nerviosa/anatomía & histología , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiología , Corteza Prefrontal/anatomía & histología , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiología , Sustancia Blanca/anatomía & histología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/fisiología , Adulto JovenRESUMEN
The common marmoset (Callithrix jacchus) is a New-World monkey of growing interest in neuroscience. Magnetic resonance imaging (MRI) is an essential tool to unveil the anatomical and functional organization of the marmoset brain. To facilitate identification of regions of interest, it is desirable to register MR images to an atlas of the brain. However, currently available atlases of the marmoset brain are mainly based on 2D histological data, which are difficult to apply to 3D imaging techniques. Here, we constructed a 3D digital atlas based on high-resolution ex-vivo MRI images, including magnetization transfer ratio (a T1-like contrast), T2w images, and multi-shell diffusion MRI. Based on the multi-modal MRI images, we manually delineated 54 cortical areas and 16 subcortical regions on one hemisphere of the brain (the core version). The 54 cortical areas were merged into 13 larger cortical regions according to their locations to yield a coarse version of the atlas, and also parcellated into 106 sub-regions using a connectivity-based parcellation method to produce a refined atlas. Finally, we compared the new atlas set with existing histology atlases and demonstrated its applications in connectome studies, and in resting state and stimulus-based fMRI. The atlas set has been integrated into the widely-distributed neuroimaging data analysis software AFNI and SUMA, providing a readily usable multi-modal template space with multi-level anatomical labels (including labels from the Paxinos atlas) that can facilitate various neuroimaging studies of marmosets.
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Atlas como Asunto , Encéfalo/anatomía & histología , Callithrix/anatomía & histología , Imagen por Resonancia Magnética/métodos , Neuroimagen/métodos , Animales , Encéfalo/diagnóstico por imagen , Corteza Cerebral/anatomía & histología , Corteza Cerebral/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética/métodos , Femenino , MasculinoRESUMEN
As a core language area, Broca's region was consistently activated in a variety of language studies even across different language systems. Moreover, a high degree of structural and functional heterogeneity in Broca's region has been reported in many studies. This raised the issue of how the intrinsic organization of Broca's region effects by different language experiences in light of its subdivisions. To address this question, we used multi-center resting-state fMRI data to explore the cross-cultural consistency and diversity of Broca's region in terms of its subdivisions, connectivity patterns and modularity organization in Chinese and German speakers. A consistent topological organization of the 13 subdivisions within the extended Broca's region was revealed on the basis of a new in-vivo parcellation map, which corresponded well to the previously reported receptorarchitectonic map. Based on this parcellation map, consistent functional connectivity patterns and modularity organization of these subdivisions were found. Some cultural difference in the functional connectivity patterns was also found, for instance stronger connectivity in Chinese subjects between area 6v2 and the motor hand area, as well as higher correlations between area 45p and middle frontal gyrus. Our study suggests that a generally invariant organization of Broca's region, together with certain regulations of different language experiences on functional connectivity, might exists to support language processing in human brain.
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Área de Broca/anatomía & histología , Área de Broca/fisiología , Comparación Transcultural , Adulto , Pueblo Asiatico , Mapeo Encefálico , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Imagen por Resonancia Magnética , Masculino , Adulto JovenRESUMEN
Social experience is essential for adolescent development and plasticity of social animals. Deprivation of the experience by social isolation impairs white matter microstructures in the prefrontal cortex. However, the effect of social isolation may involve highly distributed brain networks, and therefore cannot be fully explained by a change of a single region. Here, we compared the connectomes of adolescent socially-isolated mice and normal-housed controls via diffusion magnetic resonance imaging. The isolated mice displayed an abnormal connectome, characterized by an increase in degree and reductions in measures such as modularity, small-worldness, and betweenness. The increase in degree was most evident in the dorsolateral orbitofrontal cortex, entorhinal cortex, and perirhinal cortex. In a connection-wise comparison, we revealed that most of the abnormal edges were inter-modular and inter-hemispheric connections of the dorsolateral orbitofrontal cortex. Further tractography-based analyses and histological examinations revealed microstructural changes in the forceps minor and lateral-cortical tracts that were associated with the dorsolateral orbitofrontal cortex. These changes of connectomes were correlated with fear memory deficits and hyper-locomotion activities induced by social isolation. Considering the key role of the orbitofrontal cortex in social behaviors, adolescent social isolation may primarily disrupt the orbitofrontal cortex and its neural pathways thereby contributing to an abnormal structural connectome.
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Encéfalo/patología , Conectoma , Aislamiento Social , Animales , Condicionamiento Clásico , Imagen de Difusión por Resonancia Magnética , Miedo , Femenino , Masculino , Memoria a Corto Plazo , Ratones Endogámicos C57BL , Actividad Motora , Vías Nerviosas/patologíaRESUMEN
Drug addicts experience strong craving episodes in response to drug-associated cues. Attenuating these responses using pharmacological or behavioral approaches could aid recovery from addiction. Cue-induced drug seeking can be modeled using the conditioned place preference procedure (CPP). Our previous work showed that conditioned place preference (CPP) can be induced by administration of increasing doses of morphine in rhesus monkeys. Here, we investigated whether expression of morphine-induced CPP can be attenuated by inhibiting activity of insular cortex or by repeated unreinforced exposures to the CPP test. The insula has been demonstrated to be involved in addiction to several drugs of abuse. To test its role in morphine CPP, bilateral cannulae were implanted into the insula in seven adult monkeys. The CPP was established using a biased apparatus by intramuscular injections of morphine at increasing doses (1.5, 3.0 and 4.5mg/kg) for each monkey. After the monkeys established morphine CPP, their insulae were reversibly inactivated by bilateral microinjection with 5% lidocaine (40µl) prior to the post-conditioning test (expression) of CPP using a within-subject design. The microinjections of lidocaine failed to affect CPP expression when compared to saline injections. We subsequently investigated morphine-associated memory during six episodes of CPP tests performed in these monkeys over the following 75.0±0.2months. While the preference score showed a declining trend with repeated testing, morphine-induced CPP was maintained even on the last test performed at 75months post-conditioning. This observation indicated strong resistance of morphine-induced memories to extinction in rhesus monkeys. Although these data do not confirm involvement of insula in morphine-induced CPP, our observation that drug-associated memories can be maintained over six drug-free years following initial experience with morphine has important implications for treatment of drug addiction using extinction therapy.
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Corteza Cerebral/efectos de los fármacos , Condicionamiento Clásico/efectos de los fármacos , Extinción Psicológica/fisiología , Memoria/fisiología , Morfina/farmacología , Narcóticos/farmacología , Animales , Lidocaína/administración & dosificación , Lidocaína/farmacología , Macaca mulatta , Morfina/administración & dosificación , Narcóticos/administración & dosificación , Factores de Tiempo , Bloqueadores del Canal de Sodio Activado por Voltaje/administración & dosificación , Bloqueadores del Canal de Sodio Activado por Voltaje/farmacologíaRESUMEN
Early brain development is a complex and rapid process, the disturbance of which may cause the onset of brain disorders. Based on longitudinal imaging data acquired from 6 to 16 months postnatal, we describe a systematic trajectory of monkey brain development during late infancy, and demonstrate the influence of phencyclidine (PCP) on this trajectory. Although the general developmental trajectory of the monkey brain was close to that of the human brain, the development in monkeys was faster and regionally specific. Gray matter volume began to decrease during late infancy in monkeys, much earlier than in humans in whom it occurs in adolescence. Additionally, the decrease of gray matter volume in higher-order association regions (the frontal, parietal and temporal lobes) occurred later than in regions for primary functions (the occipital lobe and cerebellum). White matter volume displayed an increasing trend in most brain regions, but not in the occipital lobe, which had a stable volume. In addition, based on diffusion tensor imaging, we found an increase in fractional anisotropy and a decrease in diffusivity, which may be associated with myelination and axonal changes in white matter tracts. Meanwhile, we tested the influence of 14-day PCP treatment on the developmental trajectories. Such treatment tended to accelerated brain maturation during late infancy, although not statistically significant. These findings provide comparative information for the understanding of primate brain maturation and neurodevelopmental disorders.
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Encéfalo/efectos de los fármacos , Encéfalo/crecimiento & desarrollo , Antagonistas de Aminoácidos Excitadores/farmacología , Fenciclidina/farmacología , Animales , Encéfalo/anatomía & histología , Imagen de Difusión Tensora , Sustancia Gris/anatomía & histología , Sustancia Gris/efectos de los fármacos , Sustancia Gris/crecimiento & desarrollo , Macaca mulatta , Imagen por Resonancia Magnética , Masculino , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/crecimiento & desarrollo , Sustancia Blanca/anatomía & histología , Sustancia Blanca/efectos de los fármacos , Sustancia Blanca/crecimiento & desarrolloRESUMEN
The corpus callosum, historically considered primarily for homotopic connections, supports many heterotopic connections, indicating complex interhemispheric connectivity. Understanding this complexity is crucial yet challenging due to diverse cell-specific wiring patterns. Here, we utilized public AAV bulk tracing and single-neuron tracing data to delineate the anatomical connection patterns of mouse brains and conducted wide-field calcium imaging to assess functional connectivity across various brain states in male mice. The single-neuron data uncovered complex and dense interconnected patterns, particularly for interhemispheric-heterotopic connections. We proposed a metric "heterogeneity" to quantify the complexity of the connection patterns. Computational modeling of these patterns suggested that the heterogeneity of upstream projections impacted downstream homotopic functional connectivity. Furthermore, higher heterogeneity observed in interhemispheric-heterotopic projections would cause lower strength but higher stability in functional connectivity than their intrahemispheric counterparts. These findings were corroborated by our wide-field functional imaging data, underscoring the important role of heterotopic-projection heterogeneity in interhemispheric communication.
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Cuerpo Calloso , Neuronas , Animales , Cuerpo Calloso/fisiología , Masculino , Ratones , Neuronas/fisiología , Vías Nerviosas/fisiología , Conectoma , Encéfalo/fisiología , Simulación por Computador , Modelos Neurológicos , Red Nerviosa/fisiología , Calcio/metabolismoRESUMEN
Deciphering the complex relationship between neuroanatomical connections and functional activity in primate brains remains a daunting task, especially regarding the influence of monosynaptic connectivity on cortical activity. Here, we investigate the anatomical-functional relationship and decompose the neuronal-tracing connectome of marmoset brains into a series of eigenmodes using graph signal processing. These cellular connectome eigenmodes effectively constrain the cortical activity derived from resting-state functional MRI, and uncover a patterned cellular-functional decoupling. This pattern reveals a spatial gradient from coupled dorsal-posterior to decoupled ventral-anterior cortices, and recapitulates micro-structural profiles and macro-scale hierarchical cortical organization. Notably, these marmoset-derived eigenmodes may facilitate the inference of spontaneous cortical activity and functional connectivity of homologous areas in humans, highlighting the potential generalizing of the connectomic constraints across species. Collectively, our findings illuminate how neuronal-tracing connectome eigenmodes constrain cortical activity and improve our understanding of the brain's anatomical-functional relationship.
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Callithrix , Conectoma , Animales , Humanos , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Neuronas , Neuroanatomía , Imagen por Resonancia MagnéticaRESUMEN
Parvalbumin (PV) is a calcium-binding protein that labels neuronal cell bodies in the magno and parvocellular layers of the primate lateral geniculate nucleus (LGN). Here we demonstrate that PV immunohistochemistry can also be used to trace the optic radiation (OR) of the marmoset monkey (Callithrix jacchus) from its LGN origin to its destinations in the primary visual cortex (V1), thus providing a high-resolution method for identification of the OR with single axon resolution. The emergence of fibers from LGN, their entire course and even the entry points to V1 were clearly defined in coronal, parasagittal, and horizontal sections of marmoset brain. In all cases, the trajectory revealed by PV staining paralleled that defined by high-resolution diffusion tensor imaging (DTI). We found that V1 was the exclusive target for the PV-containing fibers, with abrupt transitions in staining observed in the white matter at the border with area V2, and no evidence of PV-labeled axons feeding into other visual areas. Changes in the pattern of PV staining in the OR were detected following V1 lesions, demonstrating that this method can be used to assess the progress of retrograde degeneration of geniculocortical projections. These results suggest a technically simple approach to advance our understanding of a major white matter structure, which provides a cellular resolution suitable for the detection of microstructural variations during development, health and disease. Understanding the relationship between PV staining and DTI in non-human primates may also offer clues for improving the specificity and sensitivity of OR tractography for clinical purposes.