Compromising tyrosine hydroxylase function extends and blunts the temporal profile of reinforcement by dopamine neurons in .

For a proper representation of the causal structure of the world, it is adaptive to consider both evidence for and evidence against causality. To take punishment as an example, the causality of a stimulus is unlikely if there is a temporal gap before punishment is received, but causality is credible if the stimulus immediately precedes punishment. In contrast, causality can be ruled out if the punishment occurred first.

The caloric value of food intake structurally adjusts a neuronal mushroom body circuit mediating olfactory learning in .

Associative learning enables the adaptive adjustment of behavioral decisions based on acquired, predicted outcomes. The valence of what is learned is influenced not only by the learned stimuli and their temporal relations, but also by prior experiences and internal states. In this study, we used the fruit fly to demonstrate that neuronal circuits involved in associative olfactory learning undergo restructuring during extended periods of low-caloric food intake.

Asymmetric Presynaptic Depletion of Dopamine Neurons in a Model of Parkinson's Disease.

Parkinson's disease (PD) often displays a strong unilateral predominance in arising symptoms. PD is correlated with dopamine neuron (DAN) degeneration in the substantia nigra pars compacta (SNPC), and in many patients, DANs appear to be affected more severely on one hemisphere than the other. The reason for this asymmetric onset is far from being understood.

Transneuronal Dpr12/DIP-δ interactions facilitate compartmentalized dopaminergic innervation of Drosophila mushroom body axons.

The mechanisms controlling wiring of neuronal networks are not completely understood. The stereotypic architecture of the Drosophila mushroom body (MB) offers a unique system to study circuit assembly. The adult medial MB γ-lobe is comprised of a long bundle of axons that wire with specific modulatory and output neurons in a tiled manner, defining five distinct zones.

Stochastic and Arbitrarily Generated Input Patterns to the Mushroom Bodies Can Serve as Conditioned Stimuli in .

Single neurons in the brains of insects often have individual genetic identities and can be unambiguously identified between animals. The overall neuronal connectivity is also genetically determined and hard-wired to a large degree. Experience-dependent structural and functional plasticity is believed to be superimposed onto this more-or-less fixed connectome.

Developmental Coordination during Olfactory Circuit Remodeling in Drosophila.

Developmental neuronal remodeling is crucial for proper wiring of the adult nervous system. While remodeling of individual neuronal populations has been studied, how neuronal circuits remodel-and whether remodeling of synaptic partners is coordinated-is unknown. We found that the Drosophila anterior paired lateral (APL) neuron undergoes stereotypic remodeling during metamorphosis in a similar time frame as the mushroom body (MB) ɣ-neurons, with whom it forms a functional circuit.

Neural Control of Startle-Induced Locomotion by the Mushroom Bodies and Associated Neurons in .

Startle-induced locomotion is commonly used in research to monitor locomotor reactivity and its progressive decline with age or under various neuropathological conditions. A widely used paradigm is startle-induced negative geotaxis (SING), in which flies entrapped in a narrow column react to a gentle mechanical shock by climbing rapidly upwards. Here we combined manipulation of neuronal activity and splitGFP reconstitution across cells to search for brain neurons and putative circuits that regulate this behavior.

Dopamine Modulates Serotonin Innervation in the Brain.

Parkinson's disease (PD) results from a progressive degeneration of the dopaminergic nigrostriatal system leading to a decline in movement control, with resting tremor, rigidity and postural instability. Several aspects of PD can be modeled in the fruit fly, , including α-synuclein-induced degeneration of dopaminergic neurons, or dopamine (DA) loss by genetic elimination of neural DA synthesis. Defective behaviors in this latter model can be ameliorated by feeding the DA precursor L-DOPA, analogous to the treatment paradigm for PD.

SIFamide Translates Hunger Signals into Appetitive and Feeding Behavior in Drosophila.

Animal behavior is, on the one hand, controlled by neuronal circuits that integrate external sensory stimuli and induce appropriate motor responses. On the other hand, stimulus-evoked or internally generated behavior can be influenced by motivational conditions, e.g.

Optogenetics in Drosophila Neuroscience.

Optogenetic techniques enable one to target specific neurons with light-sensitive proteins, e.g., ion channels, ion pumps, or enzymes, and to manipulate their physiological state through illumination.

Synthetic retinal analogues modify the spectral and kinetic characteristics of microbial rhodopsin optogenetic tools.

Optogenetic tools have become indispensable in neuroscience to stimulate or inhibit excitable cells by light. Channelrhodopsin-2 (ChR2) variants have been established by mutating the opsin backbone or by mining related algal genomes. As an alternative strategy, we surveyed synthetic retinal analogues combined with microbial rhodopsins for functional and spectral properties, capitalizing on assays in C.

Dopamine drives Drosophila sechellia adaptation to its toxic host.

Many insect species are host-obligate specialists. The evolutionary mechanism driving the adaptation of a species to a toxic host is, however, intriguing. We analyzed the tight association of Drosophila sechellia to its sole host, the fruit of Morinda citrifolia, which is toxic to other members of the melanogaster species group.

A dopamine receptor contributes to paraquat-induced neurotoxicity in Drosophila.

Long-term exposure to environmental oxidative stressors, like the herbicide paraquat (PQ), has been linked to the development of Parkinson's disease (PD), the most frequent neurodegenerative movement disorder. Paraquat is thus frequently used in the fruit fly Drosophila melanogaster and other animal models to study PD and the degeneration of dopaminergic neurons (DNs) that characterizes this disease. Here, we show that a D1-like dopamine (DA) receptor, DAMB, actively contributes to the fast central nervous system (CNS) failure induced by PQ in the fly.

Induction of aversive learning through thermogenetic activation of Kenyon cell ensembles in Drosophila.

Drosophila represents a model organism to analyze neuronal mechanisms underlying learning and memory. Kenyon cells of the Drosophila mushroom body are required for associative odor learning and memory retrieval. But is the mushroom body sufficient to acquire and retrieve an associative memory? To answer this question we have conceived an experimental approach to bypass olfactory sensory input and to thermogenetically activate sparse and random ensembles of Kenyon cells directly.

Differential associative training enhances olfactory acuity in Drosophila melanogaster.

Training can improve the ability to discriminate between similar, confusable stimuli, including odors. One possibility of enhancing behaviorally expressed discrimination (i.e.

A single dopamine pathway underlies progressive locomotor deficits in a Drosophila model of Parkinson disease.

Expression of the human Parkinson-disease-associated protein α-synuclein in all Drosophila neurons induces progressive locomotor deficits. Here, we identify a group of 15 dopaminergic neurons per hemisphere in the anterior medial region of the brain whose disruption correlates with climbing impairments in this model. These neurons selectively innervate the horizontal β and β' lobes of the mushroom bodies, and their connections to the Kenyon cells are markedly reduced when they express α-synuclein.

Mushroom body miscellanea: transgenic Drosophila strains expressing anatomical and physiological sensor proteins in Kenyon cells.

The fruit fly Drosophila melanogaster represents a key model organism for analyzing how neuronal circuits regulate behavior. The mushroom body in the central brain is a particularly prominent brain region that has been intensely studied in several insect species and been implicated in a variety of behaviors, e.g.

Optical calcium imaging using DNA-encoded fluorescence sensors in transgenic fruit flies, Drosophila melanogaster.

The invention of protein-based fluorescent biosensors has paved the way to target specific cells with these probes and visualize intracellular processes not only in isolated cells or tissue cultures but also in transgenic animals. In particular, DNA-encoded fluorescence proteins sensitive to Ca(2+) ions are often used to monitor changes in intracellular Ca(2+) concentrations. This is of particular relevance in neuroscience since the dynamics of intracellular Ca(2+) concentrations represents a faithful correlate for neuronal activity, and optical Ca(2+) imaging is commonly used to monitor spatiotemporal activity across populations of neurons.

The serotonergic central nervous system of the Drosophila larva: anatomy and behavioral function.

The Drosophila larva has turned into a particularly simple model system for studying the neuronal basis of innate behaviors and higher brain functions. Neuronal networks involved in olfaction, gustation, vision and learning and memory have been described during the last decade, often up to the single-cell level. Thus, most of these sensory networks are substantially defined, from the sensory level up to third-order neurons.

Optical calcium imaging in the nervous system of Drosophila melanogaster.

Background: Drosophila melanogaster is one of the best-studied model organisms in biology, mainly because of the versatility of methods by which heredity and specific expression of genes can be traced and manipulated. Sophisticated genetic tools have been developed to express transgenes in selected cell types, and these techniques can be utilized to target DNA-encoded fluorescence probes to genetically defined subsets of neurons. Neuroscientists make use of this approach to monitor the activity of restricted types or subsets of neurons in the brain and the peripheral nervous system.

Alternative oxidase rescues mitochondria-mediated dopaminergic cell loss in Drosophila.

Mitochondrial dysfunction is commonly observed in degenerative disorders, including Alzheimer's and Parkinson's disease that are characterized by the progressive and selective loss of neuronal subpopulations. It is currently unclear, however, whether mitochondrial dysfunction is primary or secondary to other pathogenic processes that eventually lead to age-related neurodegeneration. Here we establish an in vivo Drosophila model of mitochondrial dysfunction by downregulating the catalytic subunit of mitochondrial DNA (mtDNA) polymerase in cholinergic, serotonergic and dopaminergic neurons.

Behavioral consequences of dopamine deficiency in the Drosophila central nervous system.

The neuromodulatory function of dopamine (DA) is an inherent feature of nervous systems of all animals. To learn more about the function of neural DA in Drosophila, we generated mutant flies that lack tyrosine hydroxylase, and thus DA biosynthesis, selectively in the nervous system. We found that DA is absent or below detection limits in the adult brain of these flies.

Roles of dopamine in circadian rhythmicity and extreme light sensitivity of circadian entrainment.

Light has profound behavioral effects on almost all animals, and nocturnal animals show sensitivity to extremely low light levels [1-4]. Crepuscular, i.e.

Light-induced activation of distinct modulatory neurons triggers appetitive or aversive learning in Drosophila larvae.

During classical conditioning, a positive or negative value is assigned to a previously neutral stimulus, thereby changing its significance for behavior. If an odor is associated with a negative stimulus, it can become repulsive. Conversely, an odor associated with a reward can become attractive.