RESUMO
Male sexual behavior is innate and rewarding. Despite its centrality to reproduction, a molecularly specified neural circuit governing innate male sexual behavior and reward remains to be characterized. We have discovered a developmentally wired neural circuit necessary and sufficient for male mating. This circuit connects chemosensory input to BNSTprTac1 neurons, which innervate POATacr1 neurons that project to centers regulating motor output and reward. Epistasis studies demonstrate that BNSTprTac1 neurons are upstream of POATacr1 neurons, and BNSTprTac1-released substance P following mate recognition potentiates activation of POATacr1 neurons through Tacr1 to initiate mating. Experimental activation of POATacr1 neurons triggers mating, even in sexually satiated males, and it is rewarding, eliciting dopamine release and self-stimulation of these cells. Together, we have uncovered a neural circuit that governs the key aspects of innate male sexual behavior: motor displays, drive, and reward.
Assuntos
Vias Neurais , Comportamento Sexual Animal , Animais , Masculino , Neurônios/fisiologia , Recompensa , Comportamento Sexual Animal/fisiologia , CamundongosRESUMO
Social interactions require awareness and understanding of the behavior of others. Mirror neurons, cells representing an action by self and others, have been proposed to be integral to the cognitive substrates that enable such awareness and understanding. Mirror neurons of the primate neocortex represent skilled motor tasks, but it is unclear if they are critical for the actions they embody, enable social behaviors, or exist in non-cortical regions. We demonstrate that the activity of individual VMHvlPR neurons in the mouse hypothalamus represents aggression performed by self and others. We used a genetically encoded mirror-TRAP strategy to functionally interrogate these aggression-mirroring neurons. We find that their activity is essential for fighting and that forced activation of these cells triggers aggressive displays by mice, even toward their mirror image. Together, we have discovered a mirroring center in an evolutionarily ancient region that provides a subcortical cognitive substrate essential for a social behavior.
Assuntos
Agressão , Hipotálamo , Neurônios-Espelho , Animais , Camundongos , Agressão/fisiologia , Hipotálamo/citologia , Comportamento SocialRESUMO
Prairie voles are among a small group of mammals that display long-term social attachment between mating partners. Many pharmacological studies show that signaling via the oxytocin receptor (Oxtr) is critical for the display of social monogamy in these animals. We used CRISPR mutagenesis to generate three different Oxtr-null mutant prairie vole lines. Oxtr mutants displayed social attachment such that males and females showed a behavioral preference for their mating partners over a stranger of the opposite sex, even when assayed using different experimental setups. Mothers lacking Oxtr delivered viable pups, and parents displayed care for their young and raised them to the weanling stage. Together, our studies unexpectedly reveal that social attachment, parturition, and parental behavior can occur in the absence of Oxtr signaling in prairie voles.
Assuntos
Pradaria , Receptores de Ocitocina , Animais , Masculino , Feminino , Receptores de Ocitocina/genética , Ocitocina , Mamíferos , Arvicolinae , Comportamento SocialRESUMO
Sex hormones exert a profound influence on gendered behaviors. How individual sex hormone-responsive neuronal populations regulate diverse sex-typical behaviors is unclear. We performed orthogonal, genetically targeted sequencing of four estrogen receptor 1-expressing (Esr1+) populations and identified 1,415 genes expressed differentially between sexes or estrous states. Unique subsets of these genes were distributed across all 137 transcriptomically defined Esr1+ cell types, including estrous stage-specific ones, that comprise the four populations. We used differentially expressed genes labeling single Esr1+ cell types as entry points to functionally characterize two such cell types, BNSTprTac1/Esr1 and VMHvlCckar/Esr1. We observed that these two cell types, but not the other Esr1+ cell types in these populations, are essential for sex recognition in males and mating in females, respectively. Furthermore, VMHvlCckar/Esr1 cell type projections are distinct from those of other VMHvlEsr1 cell types. Together, projection and functional specialization of dimorphic cell types enables sex hormone-responsive populations to regulate diverse social behaviors.
Assuntos
Ciclo Estral/genética , Regulação da Expressão Gênica , Caracteres Sexuais , Comportamento Sexual Animal/fisiologia , Agressão , Animais , Aromatase/metabolismo , Transtorno Autístico/genética , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Feminino , Perfilação da Expressão Gênica , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Comportamento SocialRESUMO
Behaviors are inextricably linked to internal state. We have identified a neural mechanism that links female sexual behavior with the estrus, the ovulatory phase of the estrous cycle. We find that progesterone-receptor (PR)-expressing neurons in the ventromedial hypothalamus (VMH) are active and required during this behavior. Activating these neurons, however, does not elicit sexual behavior in non-estrus females. We show that projections of PR+ VMH neurons to the anteroventral periventricular (AVPV) nucleus change across the 5-day mouse estrous cycle, with â¼3-fold more termini and functional connections during estrus. This cyclic increase in connectivity is found in adult females, but not males, and regulated by estrogen signaling in PR+ VMH neurons. We further show that these connections are essential for sexual behavior in receptive females. Thus, estrogen-regulated structural plasticity of behaviorally salient connections in the adult female brain links sexual behavior to the estrus phase of the estrous cycle.
Assuntos
Rede Nervosa/fisiologia , Comportamento Sexual Animal/fisiologia , Animais , Estrogênios/metabolismo , Ciclo Estral/efeitos dos fármacos , Feminino , Hormônios Esteroides Gonadais/farmacologia , Hipotálamo Anterior/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Rede Nervosa/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ovário/metabolismo , Terminações Pré-Sinápticas/efeitos dos fármacos , Terminações Pré-Sinápticas/metabolismo , Receptores de Progesterona/metabolismo , Comportamento Sexual Animal/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fatores de TempoRESUMO
Genetically wired neural mechanisms inhibit mating between species because even naive animals rarely mate with other species. These mechanisms can evolve through changes in expression or function of key genes in sensory pathways or central circuits. Gr32a is a gustatory chemoreceptor that, in D. melanogaster, is essential to inhibit interspecies courtship and sense quinine. Similar to D. melanogaster, we find that D. simulans Gr32a is expressed in foreleg tarsi, sensorimotor appendages that inhibit interspecies courtship, and it is required to sense quinine. Nevertheless, Gr32a is not required to inhibit interspecies mating by D. simulans males. However, and similar to its function in D. melanogaster, Ppk25, a member of the Pickpocket family, promotes conspecific courtship in D. simulans. Together, we have identified distinct evolutionary mechanisms underlying chemosensory control of taste and courtship in closely related Drosophila species.
Assuntos
Evolução Biológica , Corte/psicologia , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/fisiologia , Drosophila simulans/fisiologia , Receptores de Superfície Celular/metabolismo , Comportamento Sexual Animal , Paladar/fisiologia , Animais , Comunicação Celular , Células Quimiorreceptoras , Proteínas de Drosophila/genética , Feminino , Masculino , Feromônios , Receptores de Superfície Celular/genética , ReproduçãoRESUMO
Sexually naive animals have to distinguish between the sexes because they show species-typical interactions with males and females without meaningful prior experience. However, central neural pathways in naive mammals that recognize sex of other individuals remain poorly characterized. We examined the role of the principal component of the bed nucleus of stria terminalis (BNSTpr), a limbic center, in social interactions in mice. We find that activity of aromatase-expressing BNSTpr (AB) neurons appears to encode sex of other animals and subsequent displays of mating in sexually naive males. Silencing these neurons in males eliminates preference for female pheromones and abrogates mating success, whereas activating them even transiently promotes male-male mating. Surprisingly, female AB neurons do not appear to control sex recognition, mating, or maternal aggression. In summary, AB neurons represent sex of other animals and govern ensuing social behaviors in sexually naive males.
Assuntos
Sistema Límbico/metabolismo , Núcleos Septais/fisiologia , Comportamento Sexual Animal/fisiologia , Tonsila do Cerebelo/fisiologia , Animais , Aromatase/metabolismo , Encéfalo/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Vias Neurais/metabolismo , Neurônios/metabolismo , Feromônios/metabolismo , Caracteres Sexuais , Comportamento SocialRESUMO
A long-standing goal in developmental neuroscience is to understand the mechanisms by which steroid sex hormones pattern the mammalian central nervous system along male or female pathways to enable subsequent displays of sexually dimorphic behaviors. In this article, we review recent advances in understanding the epigenetic and transcriptional mechanisms mediating sexual differentiation of the brain in mammals, flies, and worms. These studies suggest a model of sexual differentiation wherein master regulators of sex determination initiate a cascade of sexually dimorphic gene expression that controls development of neural pathways and behavioral displays in a strikingly modular manner. With these advances in molecular genetics, it is now feasible to disassemble different components of sexually dimorphic social behaviors without disrupting other behavioral interactions. Such experimental tractability promises rapid advances in this exciting field.
Assuntos
Comportamento Animal/fisiologia , Encéfalo/fisiologia , Epigênese Genética/fisiologia , Hormônios Esteroides Gonadais/fisiologia , Células Receptoras Sensoriais/fisiologia , Diferenciação Sexual/fisiologia , Comportamento Social , Animais , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Hormônios Esteroides Gonadais/metabolismoRESUMO
Sexually reproducing animals display sex differences in behavior. Although many of these sex differences in behavior are acquired with experience, sexually dimorphic behaviors such as mating and aggression are innate in the sense that they can be displayed without prior training or experience. In this review, we present recent advances in our understanding of the neural control of such innate sexually dimorphic social behaviors, with a focus on sexual behavior and aggression in flies and mice. We provide a brief overview of fundamental processes that regulate sexual differentiation in these animals to provide a framework within which more recent advances can be understood. We discuss advances in sensory, neuromodulatory, neural circuit, and experiential regulation of sexually dimorphic social behaviors.
RESUMO
How environmental and physiological signals interact to influence neural circuits underlying developmentally programmed social interactions such as male territorial aggression is poorly understood. We have tested the influence of sensory cues, social context, and sex hormones on progesterone receptor (PR)-expressing neurons in the ventromedial hypothalamus (VMH) that are critical for male territorial aggression. We find that these neurons can drive aggressive displays in solitary males independent of pheromonal input, gonadal hormones, opponents, or social context. By contrast, these neurons cannot elicit aggression in socially housed males that intrude in another male's territory unless their pheromone-sensing is disabled. This modulation of aggression cannot be accounted for by linear integration of environmental and physiological signals. Together, our studies suggest that fundamentally non-linear computations enable social context to exert a dominant influence on developmentally hard-wired hypothalamus-mediated male territorial aggression.
Assuntos
Agressão/fisiologia , Hipotálamo/citologia , Hipotálamo/fisiologia , Neurônios/fisiologia , Comportamento Social , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/genética , Adenoviridae/genética , Animais , Antipsicóticos/farmacologia , Clozapina/análogos & derivados , Clozapina/farmacologia , Canais de Cátion Regulados por Nucleotídeos Cíclicos/genética , Canais de Cátion Regulados por Nucleotídeos Cíclicos/metabolismo , Feminino , Técnicas In Vitro , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurônios/efeitos dos fármacos , Técnicas de Patch-Clamp , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Fatores Sexuais , Canais de Cátion TRPC/genética , Canais de Cátion TRPC/metabolismoRESUMO
Learning to vocalize depends on the ability to adaptively modify the temporal and spectral features of vocal elements. Neurons that convey motor-related signals to the auditory system are theorized to facilitate vocal learning, but the identity and function of such neurons remain unknown. Here we identify a previously unknown neuron type in the songbird brain that transmits vocal motor signals to the auditory cortex. Genetically ablating these neurons in juveniles disrupted their ability to imitate features of an adult tutor's song. Ablating these neurons in adults had little effect on previously learned songs but interfered with their ability to adaptively modify the duration of vocal elements and largely prevented the degradation of songs' temporal features that is normally caused by deafening. These findings identify a motor to auditory circuit essential to vocal imitation and to the adaptive modification of vocal timing.
Assuntos
Córtex Auditivo/fisiologia , Vias Auditivas/fisiologia , Aprendizagem/fisiologia , Telencéfalo/fisiologia , Vocalização Animal/fisiologia , Envelhecimento/fisiologia , Animais , Animais Geneticamente Modificados , Contagem de Células , Surdez/fisiopatologia , Tentilhões , Masculino , Vias Neurais/fisiologia , Técnicas de Rastreamento Neuroanatômico , Neurônios/fisiologiaRESUMO
Sexually reproducing animals exhibit sex differences in behavior. Sexual dimorphisms in mating, aggression, and parental care directly contribute to reproductive success of the individual and survival of progeny. In this review, we discuss recent advances in our understanding of the molecular and neural network mechanisms underlying these behaviors in mice. Notable advances include novel insights into the sensory control of social interactions and the identification of molecularly-specified neuronal populations in the brain that control mating, aggression, and parental behaviors. In the case of the latter, these advances mark a watershed because scientists can now focus on discrete neural pathways in an effort to understand how the brain encodes these fundamental social behaviors.
Assuntos
Fenômenos Fisiológicos do Sistema Nervoso , Comportamento Social , Agressão/fisiologia , Animais , Camundongos , Caracteres Sexuais , Comportamento Sexual Animal/fisiologiaRESUMO
The unique hormonal, genetic and epigenetic environments of males and females during development and adulthood shape the neural circuitry of the brain. These differences in neural circuitry result in sex-typical displays of social behaviours such as mating and aggression. Like other neural circuits, those underlying sex-typical social behaviours weave through complex brain regions that control a variety of diverse behaviours. For this reason, the functional dissection of neural circuits underlying sex-typical social behaviours has proved to be difficult. However, molecularly discrete neuronal subpopulations can be identified in the heterogeneous brain regions that control sex-typical social behaviours. In addition, the actions of oestrogens and androgens produce sex differences in gene expression within these brain regions, thereby highlighting the neuronal subpopulations most likely to control sexually dimorphic social behaviours. These conditions permit the implementation of innovative genetic approaches that, in mammals, are most highly advanced in the laboratory mouse. Such approaches have greatly advanced our understanding of the functional significance of sexually dimorphic neural circuits in the brain. In this review, we discuss the neural circuitry of sex-typical social behaviours in mice while highlighting the genetic technical innovations that have advanced the field.
Assuntos
Encéfalo/citologia , Encéfalo/fisiologia , Hormônios Esteroides Gonadais/fisiologia , Neurônios/fisiologia , Comportamento Social , Animais , Feminino , Humanos , Masculino , Fatores SexuaisRESUMO
To understand visual functions mediated by intrinsically photosensitive melanopsin-expressing retinal ganglion cells (mRGCs), it is important to elucidate axonal projections from these cells into the brain. Initial studies reported that melanopsin is expressed only in retinal ganglion cells within the eye. However, recent studies in Opn4-Cre mice revealed Cre-mediated marker expression in multiple brain areas. These discoveries complicate the use of melanopsin-driven genetic labeling techniques to identify retinofugal projections specifically from mRGCs. To restrict labeling to mRGCs, we developed a recombinant adeno-associated virus (AAV) carrying a Cre-dependent reporter (human placental alkaline phosphatase) that was injected into the vitreous of Opn4-Cre mouse eyes. The labeling observed in the brain of these mice was necessarily restricted specifically to retinofugal projections from mRGCs in the injected eye. We found that mRGCs innervate multiple nuclei in the basal forebrain, hypothalamus, amygdala, thalamus and midbrain. Midline structures tended to be bilaterally innervated, whereas the lateral structures received mostly contralateral innervation. As validation of our approach, we found projection patterns largely corresponded with previously published results; however, we have also identified a few novel targets. Our discovery of projections to the central amygdala suggests a possible direct neural pathway for aversive responses to light in neonates. In addition, projections to the accessory optic system suggest that mRGCs play a direct role in visual tracking, responses that were previously attributed to other classes of retinal ganglion cells. Moreover, projections to the zona incerta raise the possibility that mRGCs could regulate visceral and sensory functions. However, additional studies are needed to investigate the actual photosensitivity of mRGCs that project to the different brain areas. Also, there is a concern of "overlabeling" with very sensitive reporters that uncover low levels of expression. Light-evoked signaling from these cells must be shown to be of sufficient sensitivity to elicit physiologically relevant responses.