RESUMO
Anchoring goals to spatial representations enables flexible navigation but is challenging in novel environments when both representations must be acquired simultaneously. We propose a framework for how Drosophila uses internal representations of head direction (HD) to build goal representations upon selective thermal reinforcement. We show that flies use stochastically generated fixations and directed saccades to express heading preferences in an operant visual learning paradigm and that HD neurons are required to modify these preferences based on reinforcement. We used a symmetric visual setting to expose how flies' HD and goal representations co-evolve and how the reliability of these interacting representations impacts behavior. Finally, we describe how rapid learning of new goal headings may rest on a behavioral policy whose parameters are flexible but whose form is genetically encoded in circuit architecture. Such evolutionarily structured architectures, which enable rapidly adaptive behavior driven by internal representations, may be relevant across species.
Assuntos
Objetivos , Navegação Espacial , Animais , Navegação Espacial/fisiologia , Movimentos Sacádicos/fisiologia , Aprendizagem/fisiologia , Neurônios/fisiologia , Drosophila/fisiologia , Reforço Psicológico , Drosophila melanogaster/fisiologia , Condicionamento Operante/fisiologia , Rede Nervosa/fisiologiaRESUMO
Flexible behaviors over long timescales are thought to engage recurrent neural networks in deep brain regions, which are experimentally challenging to study. In insects, recurrent circuit dynamics in a brain region called the central complex (CX) enable directed locomotion, sleep, and context- and experience-dependent spatial navigation. We describe the first complete electron microscopy-based connectome of the Drosophila CX, including all its neurons and circuits at synaptic resolution. We identified new CX neuron types, novel sensory and motor pathways, and network motifs that likely enable the CX to extract the fly's head direction, maintain it with attractor dynamics, and combine it with other sensorimotor information to perform vector-based navigational computations. We also identified numerous pathways that may facilitate the selection of CX-driven behavioral patterns by context and internal state. The CX connectome provides a comprehensive blueprint necessary for a detailed understanding of network dynamics underlying sleep, flexible navigation, and state-dependent action selection.
Assuntos
Conectoma , Navegação Espacial , Animais , Encéfalo/fisiologia , Drosophila/fisiologia , Drosophila melanogaster/fisiologia , Neurônios/fisiologia , Navegação Espacial/fisiologiaRESUMO
Animals exhibit innate behaviours to a variety of sensory stimuli including olfactory cues. In Drosophila, one higher olfactory centre, the lateral horn (LH), is implicated in innate behaviour. However, our structural and functional understanding of the LH is scant, in large part due to a lack of sparse neurogenetic tools for this region. We generate a collection of split-GAL4 driver lines providing genetic access to 82 LH cell types. We use these to create an anatomical and neurotransmitter map of the LH and link this to EM connectomics data. We find ~30% of LH projections converge with outputs from the mushroom body, site of olfactory learning and memory. Using optogenetic activation, we identify LH cell types that drive changes in valence behavior or specific locomotor programs. In summary, we have generated a resource for manipulating and mapping LH neurons, providing new insights into the circuit basis of innate and learned olfactory behavior.
Assuntos
Comportamento Animal , Drosophila/anatomia & histologia , Drosophila/fisiologia , Corpos Pedunculados/anatomia & histologia , Corpos Pedunculados/fisiologia , Córtex Olfatório/anatomia & histologia , Córtex Olfatório/fisiologia , Animais , Conectoma , Vias Neurais/anatomia & histologia , Vias Neurais/fisiologia , OptogenéticaRESUMO
We have characterized a new member of the mammalian PAK family of serine/threonine kinases, PAK5, which is a novel target of the Rho GTPases Cdc42 and Rac. The kinase domain and GTPase-binding domain (GBD) of PAK5 are most closely related in sequence to those of mammalian PAK4. Outside of these domains, however, PAK5 is completely different in sequence from any known mammalian proteins. PAK5 does share considerable sequence homology with the Drosophila MBT protein (for "mushroom body tiny"), however, which is thought to play a role in development of cells in Drosophila brain. Interestingly, PAK5 is highly expressed in mammalian brain and is not expressed in most other tissues. We have found that PAK5, like Cdc42, promotes the induction of filopodia. In N1E-115 neuroblastoma cells, expression of PAK5 also triggered the induction of neurite-like processes, and a dominant-negative PAK5 mutant inhibited neurite outgrowth. Expression of activated PAK1 caused no noticeable changes in these cells. An activated mutant of PAK5 had an even more dramatic effect than wild-type PAK5, indicating that the morphologic changes induced by PAK5 are directly related to its kinase activity. Although PAK5 activates the JNK pathway, dominant-negative JNK did not inhibit neurite outgrowth. In contrast, the induction of neurites by PAK5 was abolished by expression of activated RhoA. Previous work has shown that Cdc42 and Rac promote neurite outgrowth by a pathway that is antagonistic to Rho. Our results suggest, therefore, that PAK5 operates downstream to Cdc42 and Rac and antagonizes Rho in the pathway, leading to neurite development.
Assuntos
Encéfalo/enzimologia , Neuritos/ultraestrutura , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Linhagem Celular , Clonagem Molecular , DNA Complementar/genética , Ativação Enzimática , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Dados de Sequência Molecular , Mutação , Neurônios/enzimologia , Neurônios/ultraestrutura , Fosforilação , Proteínas Serina-Treonina Quinases/química , Homologia de Sequência de Aminoácidos , Proteína cdc42 de Ligação ao GTP/metabolismo , Quinases Ativadas por p21 , Proteínas rac de Ligação ao GTP/metabolismoRESUMO
In most olfactory systems studied to date, neurons that express the same odorant receptor (Or) gene are scattered across sensory epithelia, intermingled with neurons that express different Or genes. In Drosophila, olfactory sensilla that express the same Or gene are dispersed on the antenna and the maxillary palp. Here we show that Or identity is specified in a spatially stereotyped pattern by the cell-autonomous activity of the transcriptional regulators Engrailed and Dachshund. Olfactory sensilla then become highly motile and disperse beneath the epidermis. Thus, positional information and cell motility underlie the dispersed patterns of Drosophila Or gene expression.
Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Regulação da Expressão Gênica , Proteínas de Homeodomínio/metabolismo , Proteínas Nucleares/metabolismo , Neurônios Receptores Olfatórios/fisiologia , Receptores Odorantes/metabolismo , Sensilas/fisiologia , Fatores de Transcrição/metabolismo , Animais , Animais Geneticamente Modificados , Movimento Celular , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/crescimento & desenvolvimento , Células Epidérmicas , Epiderme/metabolismo , Proteínas de Homeodomínio/genética , Mutação/genética , Proteínas Nucleares/genética , Neurônios Receptores Olfatórios/citologia , Receptores Odorantes/genética , Fatores de Transcrição/genética , Transgenes/fisiologiaRESUMO
Drosophila olfactory aversive conditioning has served as a powerful model system with which to elucidate the molecular and neuronal mechanisms underlying memory formation. In the typical protocol, flies are exposed to a constant odor stream while receiving a pulsed electric shock in the conditioning tube of a manual apparatus. We have devised a simple, low-cost semi-automated conditioning apparatus that computationally controls the delivery of odor and shock. A semiconductor-based odor sensor is employed to monitor the change of odor concentration in the training tube. The system thus allows electric shocks to be precisely matched with odor concentration in the training tube. We found that short-term memory performance was improved with a pulsed odor flow protocol, in which odor is presented in short pulses, each paired with electric shock, rather than as a constant flow. The effect of pulsed odor flow might be ascribed to the phenomenon of 'conditioned approach', where approach toward an odor is induced when the electric shock is presented before odor pulse ends. Our data shows that the system is applicable to the study of olfactory memory formation and to the examination of conditioning parameters at a level of detail not practical with a manual apparatus.