5 research outputs found
Neuropeptidergic control of innate and adaptive behaviors
No full textInnate behaviors regulate a large degree of our daily actions including feeding and escaping from noxious stimuli. Except for reflex actions, innate behaviors are not always static and can be flexibly and adaptively tuned to the animal`s current sensory context and internal state. Neuromodulators including neuropeptides are known to be key components involved in behavioral plasticity in animals. However, exactly where and how they act on innate circuits to regulate adaptive behaviors depending on context and internal state is not well understood. Drosophilamelanogaster larvae have a relatively simple nervous system but exhibit an array of innate behaviors and express conserved neuromodulators. I show here that two innate behaviors, namely noxious light avoidance, and fructose foraging, are driven by the action of a pair of central nervous system neurons (Dp7) and Insulin-like peptide 7 (Ilp7). Interestingly, Dp7 neurons and its peptide Ilp7 promote noxious light avoidance, but limit foraging behavior. I reconstructed the Dp7 neuron network at the synaptic level and showed that they receive extensive somatosensory as well as gustatory input and connect to downstream neurons related to feeding functions. In addition, I identified a local region in Dp7 neurons where noxious light is processed, likely via acute release of Ilp7 acting via the Lgr4 receptor expressed in connected downstream neurons. The identified peptidergic feedforward circuit may aid fast processing of light avoidance behavior. Moreover, I found that in the multisensory context of noxious light and fructose, hunger drives the prioritization for fructose foraging and adaptively tunes down light avoidance behavior. Conversely, sated animals preferred light avoidance to foraging behavior. I could show that this behavioral switch depends on Dp7 neuron function and its neuropeptide Ilp7. In fed animals, Ilp7 action activates the light avoidance circuit, but puts a break on the fructose foraging circuit. In starved animals, reduced Dp7 neuron and Ilp7 function likely drives fructose foraging behavior. Dp7 neurons thus act as hub neurons that integrate the sensory context in a bottom-up manner to tune avoidance and foraging.
Overall, the identified Dp7 network allows the larva to adaptively respond to its internal state and external environment, which is a key function of circuits regulating adaptive behavior in all animals
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No full textGlatt wie Samt und leuchtend in einem tiefen Rot – Psidium cattleianum, auch bekannt als die Chinesische Guave, strahlt eine majestätische Aura aus. Die Früchte, die der Strauch trägt, sind klein, saftig, süß mit einem leicht säuerlichen Geschmack, der an eine Mischung aus Erdbeeren und Litschis erinnert
A neuropeptidergic circuit gates selective escape behavior of Drosophila larvae
No full textAnimals display selective escape behaviors when faced with environmental threats. Selection of the appropriate response by the underlying neuronal network is key to maximizing chances of survival, yet the underlying network mechanisms are so far not fully understood. Using synapse-level reconstruction of the Drosophila larval network paired with physiological and behavioral readouts, we uncovered a circuit that gates selective escape behavior for noxious light through acute and input-specific neuropeptide action. Sensory neurons required for avoidance of noxious light and escape in response to harsh touch, each converge on discrete domains of neuromodulatory hub neurons. We show that acute release of hub neuron-derived insulin-like peptide 7 (Ilp7) and cognate relaxin family receptor (Lgr4) signaling in downstream neurons are required for noxious light avoidance, but not harsh touch responses. Our work highlights a role for compartmentalized circuit organization and neuropeptide release from regulatory hubs, acting as central circuit elements gating escape responses
Optimized design and in vivo application of optogenetically functionalized Drosophila dopamine receptors
No full textAbstract Neuromodulatory signaling via G protein-coupled receptors (GPCRs) plays a pivotal role in regulating neural network function and animal behavior. The recent development of optogenetic tools to induce G protein-mediated signaling provides the promise of acute and cell type-specific manipulation of neuromodulatory signals. However, designing and deploying optogenetically functionalized GPCRs (optoXRs) with accurate specificity and activity to mimic endogenous signaling in vivo remains challenging. Here we optimize the design of optoXRs by considering evolutionary conserved GPCR-G protein interactions and demonstrate the feasibility of this approach using two Drosophila Dopamine receptors (optoDopRs). These optoDopRs exhibit high signaling specificity and light sensitivity in vitro. In vivo, we show receptor and cell type-specific effects of dopaminergic signaling in various behaviors, including the ability of optoDopRs to rescue the loss of the endogenous receptors. This work demonstrates that optoXRs can enable optical control of neuromodulatory receptor-specific signaling in functional and behavioral studies
A bistable inhibitory optoGPCR for multiplexed optogenetic control of neural circuits
No full textInformation is transmitted between brain regions through the release of neurotransmitters from long-range projecting axons. Understanding how the activity of such long-range connections contributes to behavior requires efficient methods for reversibly manipulating their function. Chemogenetic and optogenetic tools, acting through endogenous G-protein-coupled receptor pathways, can be used to modulate synaptic transmission, but existing tools are limited in sensitivity, spatiotemporal precision or spectral multiplexing capabilities. Here we systematically evaluated multiple bistable opsins for optogenetic applications and found that the Platynereis dumerilii ciliary opsin (PdCO) is an efficient, versatile, light-activated bistable G-protein-coupled receptor that can suppress synaptic transmission in mammalian neurons with high temporal precision in vivo. PdCO has useful biophysical properties that enable spectral multiplexing with other optogenetic actuators and reporters. We demonstrate that PdCO can be used to conduct reversible loss-of-function experiments in long-range projections of behaving animals, thereby enabling detailed synapse-specific functional circuit mapping.|PdCO is a switchable optogenetic tool for inhibiting synaptic transmission in neuronal terminals in vivo, as demonstrated in a variety of contexts mainly in the mouse.LSEN
