Basolateral amygdala neurons facilitate reward-seeking behavior by exciting nucleus accumbens neurons

Both the nucleus accumbens (NAc) and basolateral amygdala (BLA) contribute to learned behavioral choice. Neurons in both structures that encode reward-predictive cues may underlie the decision to respond to such cues, but the neural circuits by which the BLA influences reward-seeking behavior have not been established. Here, we test the hypothesis that the BLA drives NAc neuronal responses to reward-predictive cues. First, using a disconnection experiment, we show that the BLA and dopamine projections to the NAc interact to promote the reward-seeking behavioral response. Next, we demonstrate that BLA neuronal responses to cues precede those of NAc neurons and that cue-evoked excitation of NAc neurons depends on BLA input. These results indicate that BLA input is required for dopamine to enhance the cue-evoked firing of NAc neurons and that this enhanced firing promotes reward-seeking behavior.     

Identifying behavioral circuits in Drosophila melanogaster: moving targets in a flying insect

Drosophila melanogaster has historically been the premier model system for understanding the molecular and genetic bases of complex behaviors. In the last decade technical advances, in the form of new genetic tools and electrophysiological and optical methods, have allowed investigators to begin to dissect the neuronal circuits that generate behavior in the adult. The blossoming of circuit analysis in this organism has also reinforced our appreciation of the inadequacy of wiring diagrams for specifying complex behavior. Neuromodulation and neuronal plasticity act to reconfigure circuits on both short and long time scales. These processes act on the connectome, providing context by integrating external and internal cues that are relevant for behavioral choices. New approaches in the fly are providing insight into these basic principles of circuit function.     

Neurocircuits integrating hormone and nutrient signaling in control of glucose metabolism

As obesity, diabetes, and associated comorbidities are on a constant rise, large efforts have been put into better understanding the cellular and molecular mechanisms by which nutrients and metabolic signals influence central and peripheral energy regulation. For decades, peripheral organs as a source and a target of such cues have been the focus of study. Their ability to integrate metabolic signals is essential for balanced energy and glucose metabolism. Only recently has the pivotal role of the central nervous system in the control of fuel partitioning been recognized. The rapidly expanding knowledge on the elucidation of molecular mechanisms and neuronal circuits involved is the focus of this review.     

Social modulation of fear: Facilitation vs buffering

Social behaviors largely constitute mutual exchanges of social cues and the responses to them. The adaptive response also requires proper interpretation of the current context. In fear behaviors, social signals have bidirectional effects—some cues elicit or enhance fear whereas other suppress or buffer it. Studies on the social facilitation and social buffering of fear provide evidence of competition between social cues of opposing meanings. Co‐expression of opposing cues by the same animal may explain the contradicting outcomes from the interaction between naive and frightened conspecifics, which reflect the fine balance between fear facilitation and buffering. The neuronal mechanisms that determine that balance provide an exciting target for future studies to probe the brain circuits underlying social modulation of emotional behaviors.     

Cellular bases of behavioral plasticity: establishing and modifying synaptic circuits in the Drosophila genetic system

Genetic malleability and amenability to behavioral assays make Drosophila an attractive model for dissecting the molecular mechanisms of complex behaviors, such as learning and memory. At a cellular level, Drosophila has contributed a wealth of information on the mechanisms regulating membrane excitability and synapse formation, function, and plasticity. Until recently, however, these studies have relied almost exclusively on analyses of the peripheral neuromuscular junction, with a smaller body of work on neurons grown in primary culture. These experimental systems are, by themselves, clearly inadequate for assessing neuronal function at the many levels necessary for an understanding of behavioral regulation. The pressing need is for access to physiologically relevant neuronal circuits as they develop and are modified throughout life. In the past few years, progress has been made in developing experimental approaches to examine functional properties of identified populations of Drosophila central neurons, both in cell culture and in vivo. This review focuses on these exciting developments, which promise to rapidly expand the frontiers of functional cellular neurobiology studies in Drosophila. We discuss here the technical advances that have begun to reveal the excitability and synaptic transmission properties of central neurons in flies, and discuss how these studies promise to substantially increase our understanding of neuronal mechanisms underlying behavioral plasticity.     

Integrative neuroimmunomodulation of gastrointestinal function during enteric parasitism.

Enteric helminths have a significant impact on the structure, function, and neural control of the gastrointestinal (GI) tract of the host. Interactions between the host's nervous and immune systems redirect activity in neuronal circuits intrinsic to the gut into an alternative repertoire of defensive and adaptive motor programs. Gut inflammation and activation of the enteric neuroimmune axis play integral roles in the dynamic interaction between host and parasite that occurs at the mucosal surface. Three inter-related themes are stressed in this review to underscore the pivotal role that neural control mechanisms play in the host's GI tract functional responses to enteric parasitism. First, we address the discovery that signaling molecules of both parasite and host origin can reorient the dynamic ecology of enteric host-parasite interactions. Second, we explore what has been learned from investigations of altered gut propulsive and secretomotor reflex activities that occur during enteric parasitic infections and the emerging picture derived from these studies that elucidates how nerves help facilitate and orchestrate functional reorganization of the parasitized gut. Third, we provide an overview of the direct impact that enteric parasitism has on nerve cell function and neurotransmission pathways in both the enteric and central nervous systems of the host. In summary, this review highlights and clarifies the complex mechanisms underlying integrative neuroimmunophysiological responses to the presence of both invasive and noninvasive enteric helminths and identifies directions for future research investigations in this highly important but understudied area.     

Death-associated odors induce stress in zebrafish

Living animals exploit information released from dead animals to conduct adaptive biological responses. For instance, a recently published study has shown that avoidance behavior is triggered by death-associated odors in zebrafish. Stress can clearly act as an adaptive response that allows an organism to deal with an imminent threat. However, it has not been demonstrated whether these chemical cues are stressful for fish. Here, we confirmed that dead zebrafish scents induce defensive behavior in live conspecifics. Additionally, we show for the first time in fish that these scents increase cortisol in conspecifics. To reach this conclusion, firstly, we exposed zebrafish to multi-sensorial cues (e.g., visual, tactile, chemical cues) from dead conspecifics that displayed defensive behaviors and increased cortisol. Also, when we limited zebrafish to chemical cues from dead conspecifics, similar responses arose. These responses coincide with the decaying destruction of epidermal cells, indicating that defensive and stress responses could take place as an effect of substances emanating from decaying flesh, as well as alarm substance released due to rupture of epidermal cells. Taken together, these results illustrate that living zebrafish utilize cues from dead conspecific to avoid or to cope with danger and ensure survival.     

Gap junctions

Electrical coupling through gap junctions constitutes a mode of signal transmission between neurons (electrical synaptic transmission). Originally discovered in invertebrates and in lower vertebrates, electrical synapses have recently been reported in immature and adult mammalian nervous systems. This has renewed the interest in understanding the role of electrical synapses in neural circuit function and signal processing. The present review focuses on the role of gap junctions in shaping the dynamics of neural networks by forming electrical synapses between neurons. Electrical synapses have been shown to be important elements in coincidence detection mechanisms and they can produce complex input-output functions when arranged in combination with chemical synapses. We postulate that these synapses may also be important in redefining neuronal compartments, associating anatomically distinct cellular structures into functional units. The original view of electrical synapses as static connecting elements in neural circuits has been revised and a considerable amount of evidence suggests that electrical synapses substantially affect the dynamics of neural circuits.     

Olfactory networks: from sensation to perception

Olfactory networks, comprised of sensory neurons and interneurons, detect and process changes in the chemical environment to drive animal behavior. Recent studies combining genetics with behavioral analyses and imaging in worms, flies and mice have revealed new insights into the mechanisms of olfaction. In this discussion, we focus on three interesting findings. First, sensory neuron responses to odor are modulated by neuropeptides. This modulation might serve to extend the range of responses of the sensory neurons and also to integrate internal state information into the chemosensory circuit. Second, genetic tracing studies in mice and flies have shown that the first layer of connections in chemosensory circuits from olfactory epithelium to the glomeruli are stereotyped, while the subsequent connections to higher order sensory processing regions are not. Distributed connectivity to the higher order sensory processing regions has profound implications for how odors are represented in those regions. Third, recent work has revealed that odors are surprisingly sparsely represented in the piriform cortex. The sparse coding in the higher brain centers implies a much greater role for experience and learning in mediating responses to olfactory cues. Analyzing olfactory network function in various species provides us with fascinating clues about how sensory information is acquired, processed and represented at multiple levels within the nervous system.     

Spatial Attention Effects of Disgusted and Fearful Faces

Effective processing of threat-related stimuli is of significant evolutionary advantage. Given the intricate relationship between attention and the neural processing of threat-related emotions, this study manipulated attention allocation and emotional categories of threat-related stimuli as independent factors and investigated the time course of spatial-attention-modulated processing of disgusting and fearful stimuli. The participants were instructed to direct their attention either to the two vertical or to the two horizontal locations, where two faces and two houses would be presented. The task was to respond regarding the physical identity of the two stimuli at cued locations. Event-related potentials (ERP) evidences were found to support a two-stage model of attention-modulated processing of threat-related emotions. In the early processing stage, disgusted faces evoked larger P1 component at right occipital region despite the attention allocation while larger N170 component was elicited by fearful faces at right occipito-temporal region only when participants attended to houses. In the late processing stage, the amplitudes of the parietal P3 component enhanced for both disgusted and fearful facial expressions only when the attention was focused on faces. According to the results, we propose that the temporal dynamics of the emotion-by-attention interaction consist of two stages. The early stage is characterized by quick and specialized neural encoding of disgusting and fearful stimuli irrespective of voluntary attention allocation, indicating an automatic detection and perception of threat-related emotions. The late stage is represented by attention-gated separation between threat-related stimuli and neutral stimuli; the similar ERP pattern evoked by disgusted and fearful faces suggests a more generalized processing of threat-related emotions via top-down attentional modulation, based on which the defensive behavior in response to threat events is largely facilitated.     

Functional mapping of neurons that control locomotory behavior in Caenorhabditis elegans

One approach to understanding behavior is to define the cellular components of neuronal circuits that control behavior. In the nematode Caenorhabditis elegans, neuronal circuits have been delineated based on patterns of synaptic connectivity derived from ultrastructural analysis. Individual cellular components of these anatomically defined circuits have previously been characterized on the sensory and motor neuron levels. In contrast, interneuron function has only been addressed to a limited extent. We describe here several classes of interneurons (AIY, AIZ, and RIB) that modulate locomotory behavior in C. elegans. Using mutant analysis as well as microsurgical mapping techniques, we found that the AIY neuron class serves to tonically modulate reversal frequency of animals in various sensory environments via the repression of the activity of a bistable switch composed of defined command interneurons. Furthermore, we show that the presentation of defined sensory modalities induces specific alterations in reversal behavior and that the AIY interneuron class mediates this alteration in locomotory behavior. We also found that the AIZ and RIB interneuron classes process odorsensory information in parallel to the AIY interneuron class. AIY, AIZ, and RIB are the first interneurons directly implicated in chemosensory signaling. Our neuronal mapping studies provide the framework for further genetic and functional dissections of neuronal circuits in C. elegans.     

Interspecific variation in the defensive responses of obligate plant-ants: experimental tests and consequences for herbivory

The aggressive behavior of ants that protect plants from herbivores in exchange for rewards such as shelter or food is thought to be an important form of biotic defense against herbivory, particularly in tropical systems. To date, however, no one has compared the defensive responses of different ant taxa associated with the same plant species, and attempted to relate these differences to longer-term efficacy of ant defense. We used experimental cues associated with herbivory—physical damage and extracts of chemical volatiles from leaf tissue—to compare the aggressive responses of two ant species obligately associated with the Amazonian myrmecophyte Tococa bullifera (Melastomataceae). We also conducted a colony removal experiment to quantify the level of resistance from herbivores provided to plants by each ant species. Our experiments demonstrate that some cues eliciting a strong response from one ant species elicited no response by the other. For cues that do elicit responses, the magnitude of these responses can vary interspecifically. These patterns were consistent with the level of resistance provided from herbivores to plants. The colony removal experiment showed that both ant species defend plants from herbivores: however, herbivory was higher on plants colonized by the less aggressive ant species. Our results add to the growing body of literature indicating defensive ant responses are stimulated by cues associated with herbivory. However, they also suggest the local and regional variation in the composition of potential partner taxa could influence the ecology and evolution of defensive mutualisms in ways that have previously remained unexplored.     

Evolution and development of neural circuits in invertebrates

Developmental mechanisms can shed light on how evolutionary diversity has arisen. Invertebrate nervous systems offer a wealth of diverse structures and functions from which to relate development to evolution. Individual homologous neurons have been shown to have distinct roles in species with different behaviors. In addition, specific neurons have been lost or gained in some phylogenetic lineages. The ability to address the neural basis of behavior at the cellular level in invertebrates has facilitated discoveries showing that species-specific behavior can arise from differences in synaptic strength, in neuronal structure and in neuromodulation. The mechanisms involved in the development of neural circuits lead to these differences across species.     

Building neural choice points for love and war

The molecular specification of central circuits that coordinate expression of innate behaviors in response to specific sensory cues from the environment remains a puzzle. In this issue of Neuron, Choi, Dong, and colleagues used expression profiling and genetic axonal tracing to visualize a hypothalamic point of convergence for defensive and reproductive olfactory cues that may function as a gating mechanism for sensory activation of defensive responses over reproduction.     

Addiction: Decreased reward sensitivity and increased expectation sensitivity conspire to overwhelm the brain's control circuit

Based on brain imaging findings, we present a model according to which addiction emerges as an imbalance in the information processing and integration among various brain circuits and functions. The dysfunctions reflect (a) decreased sensitivity of reward circuits, (b) enhanced sensitivity of memory circuits to conditioned expectations to drugs and drug cues, stress reactivity, and (c) negative mood, and a weakened control circuit. Although initial experimentation with a drug of abuse is largely a voluntary behavior, continued drug use can eventually impair neuronal circuits in the brain that are involved in free will, turning drug use into an automatic compulsive behavior. The ability of addictive drugs to co‐opt neurotransmitter signals between neurons (including dopamine, glutamate, and GABA) modifies the function of different neuronal circuits, which begin to falter at different stages of an addiction trajectory. Upon exposure to the drug, drug cues or stress this results in unrestrained hyperactivation of the motivation/drive circuit that results in the compulsive drug intake that characterizes addiction.     

Context-dependent control of behavior in Drosophila

The representation of contextual information peripheral to a salient stimulus is central to an animal's ability to correctly interpret and flexibly respond to that stimulus. While the computations and circuits underlying the context-dependent modulation of stimulus-response pairings have typically been studied in vertebrates, the genetic tractability, numeric simplification, and well-characterized connectivity patterns of the Drosophila melanogaster brain have facilitated circuit-level insights into contextual processing. Recent studies in flies reveal the neuronal mechanisms that create flexible context-dependent behavioral responses to sensory events in conditions of predation threat, feeding regulation, and social interaction.     

The neural circuits and synaptic mechanisms underlying motor initiation in C. elegans

C. elegans is widely used to dissect how neural circuits and genes generate behavior. During locomotion, worms initiate backward movement to change locomotion direction spontaneously or in response to sensory cues; however, the underlying neural circuits are not well defined. We applied a multidisciplinary approach to map neural circuits in freely behaving worms by integrating functional imaging, optogenetic interrogation, genetic manipulation, laser ablation, and electrophysiology. We found that a disinhibitory circuit and a stimulatory circuit together promote initiation of backward movement and that circuitry dynamics is differentially regulated by sensory cues. Both circuits require glutamatergic transmission but depend on distinct glutamate receptors. This dual mode of motor initiation control is found in mammals, suggesting that distantly related organisms with anatomically distinct nervous systems may adopt similar strategies for motor control. Additionally, our studies illustrate how a multidisciplinary approach facilitates dissection of circuit and synaptic mechanisms underlying behavior in a genetic model organism.