RESUMO
This review explores the role of aromatase in the brain as illuminated by a set of conserved network-level connections identified in several vertebrate taxa. Aromatase-expressing neurons are neurochemically heterogeneous but the brain regions in which they are found are highly-conserved across the vertebrate lineage. During development, aromatase neurons have a prominent role in sexual differentiation of the brain and resultant sex differences in behavior and human brain diseases. Drawing on literature primarily from birds and rodents, we delineate brain regions that express aromatase and that are strongly interconnected, and suggest that, in many species, aromatase expression essentially defines the Social Behavior Network. Moreover, in several cases the inputs to and outputs from this core Social Behavior Network also express aromatase. Recent advances in molecular and genetic tools for neuroscience now enable in-depth and taxonomically diverse studies of the function of aromatase at the neural circuit level.
Assuntos
Aromatase , Encéfalo , Animais , Aromatase/metabolismo , Encéfalo/metabolismo , Feminino , Masculino , Neurônios/metabolismo , Caracteres Sexuais , Comportamento SocialRESUMO
Mice display robust, stereotyped behaviours towards pups: virgin males typically attack pups, whereas virgin females and sexually experienced males and females display parental care. Here we show that virgin males genetically impaired in vomeronasal sensing do not attack pups and are parental. Furthermore, we uncover a subset of galanin-expressing neurons in the medial preoptic area (MPOA) that are specifically activated during male and female parenting, and a different subpopulation that is activated during mating. Genetic ablation of MPOA galanin neurons results in marked impairment of parental responses in males and females and affects male mating. Optogenetic activation of these neurons in virgin males suppresses inter-male and pup-directed aggression and induces pup grooming. Thus, MPOA galanin neurons emerge as an essential regulatory node of male and female parenting behaviour and other social responses. These results provide an entry point to a circuit-level dissection of parental behaviour and its modulation by social experience.
Assuntos
Galanina/metabolismo , Comportamento Materno/fisiologia , Neurônios/metabolismo , Comportamento Paterno/fisiologia , Área Pré-Óptica/citologia , Agressão/fisiologia , Animais , Copulação , Feminino , Galanina/deficiência , Galanina/genética , Asseio Animal/fisiologia , Masculino , Camundongos , Optogenética , Feromônios/análise , Área Pré-Óptica/metabolismo , Canais de Cátion TRPC/deficiência , Canais de Cátion TRPC/genética , Órgão Vomeronasal/fisiologiaRESUMO
Mammalian circadian rhythms are entrained by photic stimuli that are relayed by retinal projections to the core of the suprachiasmatic nucleus (SCN). Neuronal activation, as demonstrated by expression of the immediate early gene c-fos, leads to transcription of the core clock gene per1. The duper mutation in hamsters shortens circadian period and amplifies light-induced phase shifts. We performed two experiments to compare the number of c-FOS immunoreactive (ir) and PER1-ir cells, and the intensity of staining, in the SCN of wild-type (WT) and duper hamsters at various intervals after presentation of a 15-min light pulse in the early subjective night. Light-induced c-FOS-ir within 1 hr in the dorsocaudal SCN of duper, but not WT hamsters. In cells that express vasoactive intestinal peptide (VIP), which plays a critical role in synchronization of SCN cellular oscillators, light-induced c-FOS-ir was greater in duper than WT hamsters. After the light pulse, PER1-ir cells were found in more medial portions of the SCN than FOS-ir, and appeared with a longer latency and over a longer time course, in VIP cells of duper than wild-type hamsters. Our results indicate that the duper allele alters SCN function in ways that may contribute to changes in free running period and phase resetting.
Assuntos
Ritmo Circadiano/fisiologia , Atividade Motora/fisiologia , Núcleo Supraquiasmático/metabolismo , Peptídeo Intestinal Vasoativo/metabolismo , Animais , Cricetinae , Genes fos/genética , Imuno-Histoquímica/métodos , Masculino , Mutação/genética , Neurônios/metabolismo , Proteínas Circadianas Period/metabolismo , Estimulação Luminosa , Proteínas Proto-Oncogênicas c-fos/metabolismoRESUMO
Arginine vasopressin (AVP) is a neuropeptide critical for the mammalian stress response and social behavior. AVP produced in the hypothalamus regulates water osmolality and vasoconstriction in the body, and in the brain, it regulates social behavior, aggression, and anxiety. However, the circuit mechanisms that link AVP to social behavior, homeostatic function, and disease are not well understood. This study investigates the circuit configurations of AVP-expressing neurons in the rodent hypothalamus and characterizes synaptic input from the entire brain. We targeted the paraventricular nucleus (PVN) using retrograde viral tracing techniques to identify direct afferent synaptic connections made onto AVP-expressing neurons. AVP neurons in the PVN display region-specific anatomical configurations that reflect their unique contributions to homeostatic function, motor behaviors, feeding, and affiliative behavior. The afferent connections identified were similar in both sexes and subsequent molecular investigation of these inputs shows that those local hypothalamic inputs are overwhelmingly nonpeptidergic cells indicating a potential interneuron nexus between hormone cell activation and broader cortical connection. This proposed work reveals new insights into the organization of social behavior circuits in the brain, and how neuropeptides act centrally to modulate social behaviors.
Assuntos
Hipotálamo , Núcleo Hipotalâmico Paraventricular , Masculino , Feminino , Animais , Núcleo Hipotalâmico Paraventricular/metabolismo , Hipotálamo/metabolismo , Vasopressinas/metabolismo , Arginina Vasopressina/metabolismo , Neurônios/metabolismo , Encéfalo/metabolismoRESUMO
The accessory olfactory bulb (AOB) plays a critical role in classifying pheromonal signals. Here we identify two previously undescribed sources of aromatase signaling in the AOB: (1) a population of aromatase-expressing neurons in the AOB itself; (2) a tract of aromatase-expressing axons which originate in the ventral medial amygdala (MEA) and terminate in the AOB. Using a retrograde tracer in conjunction with a transgenic strategy to label aromatase-expressing neurons throughout the brain, we found that a single contiguous population of neurons in the ventral MEA provides the only significant feedback by aromatase-expressing neurons to the AOB. This population expresses the estrogen receptor alpha (ERα) and displayed anatomical sex differences in the number of neurons (higher in male mice) and the size of cell bodies (larger in females). Given the previously established relationship between aromatase expression, estrogen signaling, and the function of sexually dimorphic circuits, we suggest that this feedback population is well-positioned to provide neuroendocrine feedback to modulate sensory processing of social stimuli in the AOB.
Assuntos
Bulbo Olfatório , Órgão Vomeronasal , Tonsila do Cerebelo/metabolismo , Animais , Aromatase/metabolismo , Retroalimentação , Feminino , Masculino , Camundongos , Neurônios/metabolismo , Bulbo Olfatório/metabolismo , Órgão Vomeronasal/metabolismoRESUMO
Here, we reveal an unbiased view of the brain regions that provide specific inputs to aromatase-expressing cells in the medial amygdala, neurons that play an outsized role in the production of sex-specific social behaviors, using rabies tracing and light sheet microscopy. While the downstream projections from these cells are known, the specific inputs to the aromatase-expressing cells in the medial amygdala remained unknown. We observed established connections to the medial amygdala (e.g., bed nucleus of the stria terminalis and accessory olfactory bulb) indicating that aromatase neurons are a major target cell type for efferent input including from regions associated with parenting and aggression. We also identified novel and unexpected inputs from areas involved in metabolism, fear and anxiety, and memory and cognition. These results confirm the central role of the medial amygdala in sex-specific social recognition and social behavior, and point to an expanded role for its aromatase-expressing neurons in the integration of multiple sensory and homeostatic factors, which are likely used to modulate many other social behaviors.
Assuntos
Aromatase , Complexo Nuclear Corticomedial , Tonsila do Cerebelo/fisiologia , Aromatase/metabolismo , Feminino , Humanos , Masculino , Neurônios/metabolismo , Comportamento SocialRESUMO
Complex social behaviors are emergent properties of the brain's interconnected and overlapping neural networks. Questions aimed at understanding how brain circuits produce specific and appropriate behaviors have changed over the past half century, shifting from studies of gross anatomical and behavioral associations, to manipulating and monitoring precisely targeted cell types. This technical progression has enabled increasingly deep insights into the regulation of perception and behavior with remarkable precision. The capacity of reductionist approaches to identify the function of isolated circuits is undeniable but many behaviors require rapid integration of diverse inputs. This review examines progress toward understanding integrative social circuits and focuses on specific nodes of the social behavior network including the medial amygdala, ventromedial hypothalamus (VMH) and medial preoptic area of the hypothalamus (MPOA) as examples of broad integration between multiple interwoven brain circuits. Our understanding of mechanisms for producing social behavior has deepened in conjunction with advances in technologies for visualizing and manipulating specific neurons and, here, we consider emerging strategies to address brain circuit function in the context of integrative anatomy.
RESUMO
Techniques used to clear biological tissue for fluorescence microscopy are essential to connect anatomical principles at levels ranging from subcellular to the whole animal. Here we report a simple and straightforward approach to efficiently render opaque tissue samples transparent and show that this approach can be modified to rapidly label intact tissue samples with antibodies for large volume fluorescence microscopy. This strategy applies a magnetohydrodynamic (MHD) force to accelerate the removal of lipids from tissue samples at least as large as an intact adult mouse brain. We also show that MHD force can be used to accelerate antibody penetration into tissue samples. This strategy complements a growing array of tools that enable high-resolution 3-dimensional anatomical analyses in intact tissues using fluorescence microscopy. MHD-accelerated clearing is simple, fast, reliable, inexpensive, provides good thermal regulation, and is compatible with existing strategies for high-quality fluorescence microscopy of intact tissues.
Assuntos
Encéfalo/metabolismo , Hidrodinâmica , Magnetismo , Animais , Camundongos , Microscopia de Fluorescência/métodosRESUMO
The optic tectum of the barn owl contains a map of auditory space. We found that, in response to moving sounds, the locations of receptive fields that make up the map shifted toward the approaching sound. The magnitude of the receptive field shifts increased systematically with increasing stimulus velocity and, therefore, was appropriate to compensate for sensory and motor delays inherent to auditory orienting behavior. Thus, the auditory space map is not static, but shifts adaptively and dynamically in response to stimulus motion. We provide a computational model to account for these results. Because the model derives predictive responses from processes that are known to occur commonly in neural networks, we hypothesize that analogous predictive responses will be found to exist widely in the central nervous system. This hypothesis is consistent with perceptions of stimulus motion in humans for many sensory parameters.
Assuntos
Percepção Auditiva/fisiologia , Localização de Som/fisiologia , Percepção Espacial/fisiologia , Estrigiformes/fisiologia , Adaptação Fisiológica/fisiologia , Algoritmos , Animais , Simulação por Computador , Interpretação Estatística de Dados , Eletrofisiologia , Microeletrodos , Modelos Neurológicos , Modelos Estatísticos , Percepção de Movimento/fisiologia , Colículos Superiores/fisiologiaRESUMO
The brains of male and female mice are shaped by genetics and hormones during development. The enzyme aromatase helps establish sex differences in social behaviors and in the neural circuits that produce these behaviors. The medial amygdala of mice contains a large population of aromatase neurons and is a critical hub in the social behavior network. Moreover, the neural representation of social stimuli in the medial amygdala displays clear sex differences that track developmental changes in social behaviors. Here, we identify a potential anatomic basis for those sex differences. We found that sensory input from the accessory olfactory bulb (AOB) to aromatase neurons is derived nearly exclusively from the anterior AOB, which selectively responds to chemosensory cues from conspecific animals. Through the coordinated use of mouse transgenics and viral-based circuit-tracing strategies, we demonstrate a clear sex difference in the volume of synapses connecting the accessory olfactory bulb to aromatase-expressing neurons in the medial amygdala of male versus female mice. This difference in anatomy likely mediates, at least in part, sex differences in medial amygdala-mediated social behaviors.
Assuntos
Aromatase , Complexo Nuclear Corticomedial , Tonsila do Cerebelo , Animais , Aromatase/genética , Feminino , Masculino , Camundongos , Bulbo Olfatório , Comportamento SocialRESUMO
Neurons in the brain of a female mouse that respond to the scent of a given male become suppressed after mating.
Assuntos
Aprendizado Social , Animais , Encéfalo , Feminino , Masculino , Camundongos , Neurônios , Odorantes , FeromôniosRESUMO
In this issue, Ishii and colleagues identify an anatomically and genetically defined circuit by which a single compound, exocrine gland-secreted peptide-1 (ESP1), enhances reproductive behavior in female mice.
Assuntos
Peptídeos , Comportamento Sexual , Animais , Feminino , CamundongosRESUMO
The neural control of social behaviors in rodents requires the encoding of pheromonal cues by the vomeronasal system. Here we show that the typical preference of male mice for females is eliminated in mutants lacking oxytocin, a neuropeptide modulating social behaviors in many species. Ablation of the oxytocin receptor in aromatase-expressing neurons of the medial amygdala (MeA) fully recapitulates the elimination of female preference in males. Further, single-unit recording in the MeA uncovered significant changes in the sensory representation of conspecific cues in the absence of oxytocin signaling. Finally, acute manipulation of oxytocin signaling in adults is sufficient to alter social interaction preferences in males as well as responses of MeA neurons to chemosensory cues. These results uncover the critical role of oxytocin signaling in a molecularly defined neuronal population in order to modulate the behavioral and physiological responses of male mice to females on a moment-to-moment basis.
Assuntos
Tonsila do Cerebelo/fisiologia , Ocitocina/farmacologia , Receptores de Ocitocina/fisiologia , Células Receptoras Sensoriais/fisiologia , Comportamento Sexual Animal/efeitos dos fármacos , Comportamento Social , Tonsila do Cerebelo/citologia , Tonsila do Cerebelo/efeitos dos fármacos , Animais , Células Cultivadas , Sinais (Psicologia) , Discriminação Psicológica , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ocitócicos/farmacologia , Células Receptoras Sensoriais/citologia , Células Receptoras Sensoriais/efeitos dos fármacosRESUMO
Understanding physical and chemical processes at an organismal scale is a fundamental goal in biology. While science is adept at explaining biological phenomena at both molecular and cellular levels, understanding how these processes translate to organismal functions remains a challenging problem. This issue is particularly significant for the nervous system where cell signaling and synaptic activities function in the context of broad neural networks. Recent progress in tissue clearing technologies lessens the barriers that previously prevented the study of large tissue samples while maintaining molecular and cellular resolution. While these new methods open vast opportunities and exciting new questions, the logistics of analyzing cellular processes in intact tissue have to be carefully considered. In this protocol, we outline a procedure to rapidly image intact brain tissue up to thousands of cubic millimeters. This experimental pipeline involves three steps: tissue clearing, tissue imaging, and data analysis. In an attempt to streamline the process for researchers entering this field, we address important considerations for each of these stages and describe an integrated solution to image intact biological tissues. Hopefully, this optimized protocol will lower the barrier of implementing high-resolution tissue imaging and facilitate the investigations of mesoscale questions at molecular and cellular resolution.
Assuntos
Microscopia/métodos , Tecido Nervoso/citologia , Tecido Nervoso/metabolismo , Neuroimagem/métodos , Animais , Biomarcadores , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional/métodos , Armazenamento e Recuperação da Informação , Camundongos , Neurônios/citologia , Neurônios/metabolismo , SoftwareRESUMO
The optic tectum (OT) of barn owls contains topographic maps of auditory and visual space. Barn owls reared with horizontally displacing prismatic spectacles (prisms) acquire a novel auditory space map in the OT that restores alignment with the prismatically displaced visual map. Although juvenile owls readily acquire alternative maps of auditory space as a result of experience, this plasticity is reduced greatly in adults. We tested whether hunting live prey, a natural and critically important behavior for barn owls, increases auditory map plasticity in adult owls. Two groups of naive adult owls were fit with prisms. The first group was fed dead mice during 10 weeks of prism experience, while the second group was required to hunt live prey for an identical period of time. When the owls hunted live prey, auditory maps shifted substantially farther (five times farther, on average) and the consistency of tuning curve shifts within each map increased. Only a short period of time in each day, during which the two groups experienced different conditions, accounts for this effect. In addition, increased map plasticity correlated with behavioral improvements in the owls' ability to strike and capture prey. These results indicate that the experience of hunting dramatically increases adult adaptive plasticity in this pathway.
Assuntos
Vias Auditivas/fisiologia , Mapeamento Encefálico/métodos , Plasticidade Neuronal/fisiologia , Comportamento Predatório/fisiologia , Estrigiformes/fisiologia , Estimulação Acústica/métodos , Adaptação Fisiológica/fisiologia , Animais , Percepção Auditiva/fisiologia , Localização de Som/fisiologiaRESUMO
Social behaviors are as diverse as the animals that employ them, with some behaviors, like affiliation and aggression, expressed in nearly all social species. Whether discussing a "family" of beavers or a "murder" of crows, the elaborate language we use to describe social animals immediately hints at patterns of behavior typical of each species. Neuroscience has now revealed a core network of regions of the brain that are essential for the production of social behavior. Like the behaviors themselves, neuromodulation and hormonal changes regulate the underlying neural circuits on timescales ranging from momentary events to an animal's lifetime. Dynamic and heavily interconnected social circuits provide a distinct challenge for developing a mechanistic understanding of social behavior. However, advances in neuroscience continue to generate an explanation of social behavior based on the electrical activity and synaptic connections of neurons embedded in defined neural circuits.
Assuntos
Invertebrados/fisiologia , Fenômenos Fisiológicos do Sistema Nervoso , Comportamento Social , Vertebrados/fisiologia , AnimaisRESUMO
Combining rabies-virus tracing, optical clearing (CLARITY), and whole-brain light-sheet imaging, we mapped the monosynaptic inputs to midbrain dopamine neurons projecting to different targets (different parts of the striatum, cortex, amygdala, etc) in mice. We found that most populations of dopamine neurons receive a similar set of inputs rather than forming strong reciprocal connections with their target areas. A common feature among most populations of dopamine neurons was the existence of dense 'clusters' of inputs within the ventral striatum. However, we found that dopamine neurons projecting to the posterior striatum were outliers, receiving relatively few inputs from the ventral striatum and instead receiving more inputs from the globus pallidus, subthalamic nucleus, and zona incerta. These results lay a foundation for understanding the input/output structure of the midbrain dopamine circuit and demonstrate that dopamine neurons projecting to the posterior striatum constitute a unique class of dopamine neurons regulated by different inputs.
Assuntos
Encéfalo/anatomia & histologia , Corpo Estriado/anatomia & histologia , Neurônios Dopaminérgicos/fisiologia , Vias Neurais/anatomia & histologia , Vias Neurais/fisiologia , Animais , CamundongosRESUMO
Animal-animal recognition within, and across species, is essential for predator avoidance and social interactions. Despite its essential role in orchestrating responses to animal cues, basic principles of information processing by the vomeronasal system are still unknown. The medial amygdala (MeA) occupies a central position in the vomeronasal pathway, upstream of hypothalamic centers dedicated to defensive and social responses. We have characterized sensory responses in the mouse MeA and uncovered emergent properties that shed new light onto the transformation of vomeronasal information into sex- and species-specific responses. In particular, we show that the MeA displays a degree of stimulus selectivity and a striking sexually dimorphic sensory representation that are not observed in the upstream relay of the accessory olfactory bulb (AOB). Furthermore, our results demonstrate that the development of sexually dimorphic circuits in the MeA requires steroid signaling near the time of puberty to organize the functional representation of sensory stimuli.DOI: http://dx.doi.org/10.7554/eLife.02743.001.
Assuntos
Tonsila do Cerebelo/fisiologia , Fatores Sexuais , Animais , Sinais (Psicologia) , Feminino , Hormônios/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neurônios/metabolismo , Odorantes , Bulbo Olfatório/fisiologia , Mucosa Olfatória/fisiologia , Comportamento Sexual Animal/fisiologia , Órgão Vomeronasal/fisiologiaRESUMO
Determination of the molecular architecture of synapses requires nanoscopic image resolution and specific molecular recognition, a task that has so far defied many conventional imaging approaches. Here, we present a superresolution fluorescence imaging method to visualize the molecular architecture of synapses in the brain. Using multicolor, three-dimensional stochastic optical reconstruction microscopy, the distributions of synaptic proteins can be measured with nanometer precision. Furthermore, the wide-field, volumetric imaging method enables high-throughput, quantitative analysis of a large number of synapses from different brain regions. To demonstrate the capabilities of this approach, we have determined the organization of ten protein components of the presynaptic active zone and the postsynaptic density. Variations in synapse morphology, neurotransmitter receptor composition, and receptor distribution were observed both among synapses and across different brain regions. Combination with optogenetics further allowed molecular events associated with synaptic plasticity to be resolved at the single-synapse level.
Assuntos
Encéfalo/ultraestrutura , Imageamento Tridimensional/métodos , Microscopia de Fluorescência/métodos , Proteínas do Tecido Nervoso/ultraestrutura , Terminações Pré-Sinápticas/ultraestrutura , Animais , Encéfalo/metabolismo , Química Encefálica/fisiologia , Processamento de Imagem Assistida por Computador/instrumentação , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/instrumentação , Imuno-Histoquímica/métodos , Camundongos , Camundongos Endogâmicos C57BL , Microquímica/métodos , Microscopia de Fluorescência/instrumentação , Imagem Molecular/instrumentação , Imagem Molecular/métodos , Nanotecnologia , Proteínas do Tecido Nervoso/metabolismo , Plasticidade Neuronal/fisiologia , Fotomicrografia/instrumentação , Fotomicrografia/métodos , Terminações Pré-Sinápticas/metabolismo , Processos Estocásticos , Sinapses/metabolismo , Sinapses/ultraestruturaRESUMO
The barn owl's central auditory system creates a map of auditory space in the external nucleus of the inferior colliculus (ICX). Although the crucial role visual experience plays in the formation and maintenance of this auditory space map is well established, the mechanism by which vision influences ICX responses remains unclear. Surprisingly, previous experiments have found that in the absence of extensive pharmacological manipulation, visual stimuli do not drive neural responses in the ICX. Here we investigated the influence of dynamic visual stimuli on auditory responses in the ICX. We show that a salient visual stimulus, when coincident with an auditory stimulus, can modulate auditory responses in the ICX even though the same visual stimulus may elicit no neural responses when presented alone. For each ICX neuron, the most effective auditory and visual stimuli were located in the same region of space. In addition, the magnitude of the visual modulation of auditory responses was dependent on the context of the stimulus presentation with novel visual stimuli eliciting consistently larger response modulations than frequently presented visual stimuli. Thus the visual modulation of ICX responses is dependent on the characteristics of the visual stimulus as well as on the spatial and temporal correspondence of the auditory and visual stimuli. These results demonstrate moment-to-moment visual enhancements of auditory responsiveness that, in the short-term, increase auditory responses to salient bimodal stimuli and in the long-term could serve to instruct the adaptive auditory plasticity necessary to maintain accurate auditory orienting behavior.