Model organism | EPFL Graph Search

A model organism (often shortened to model) is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workings of other organisms. Model organisms are widely used to research human disease when human experimentation would be unfeasible or unethical. This strategy is made possible by the common descent of all living organisms, and the conservation of metabolic and developmental pathways and genetic material over the course of evolution. Studying model organisms can be informative, but care must be taken when generalizing from one organism to another. In researching human disease, model organisms allow for better understanding the disease process without the added risk of harming an actual human. The species chosen will usually meet a determined taxonomic equivalency to humans, so as to react to disease or its treatment in a way that resembles human

Methods for acute and long-term imaging of the ventral nerve cord in behaving adult Drosophila

Laura Joan Hermans

Understanding how neural circuits remodel and adapt to animal behavior is a central theme in the field of Neuroscience. One strategy to reach this goal is to repeatedly record the same animal's neural circuits and observe how they adapt when facing different challenges. Research has primarily focused on identifying neural circuits and connectivity maps within the brains of model organisms. Nevertheless, it has become evident that functional recordings are essential to have a complete understanding of how neural circuits generate behaviors. Numerous techniques have been introduced to record activity from brain circuits in model animals spanning from monkeys to insects. However, imaging the spinal cord in mammals or the ventral nerve cord in insects remains an open challenge due to the complexity of obtaining optical access without impacting the animal's behavior and damaging neural tissues. As a result, we have very limited information on how neural circuits in the spinal cord generate behaviors and how they adapt to different experiences such as injury or aging. Drosophila is a perfect model organism for carrying out this line of research thanks to its small size, genetically tractable nervous system, and behavioral diversity. The results are relevant to human physiology and behavior as many mechanisms have homologs in mammals. What is missing is a technological advancement that allows recording of behavior, structural changes in the circuits, and spatiotemporal dynamics of neural activity on the same animal.This thesis addresses this gap and introduces two novel methods for in vivo functional recordings of the fly's ventral nerve cord (VNC). The first one gains short-term access to the fly's VNC using a novel dissection preparation. The second one enables long-term functional recordings of the fly's VNC thanks to a toolkit combining four microengineered devices: a surgical arm, a V-shape implant, an optically transparent and numbered window and a remounting stage. The toolkit is suitable for both male and female flies and provides optical access to the VNC for at least one month. Additionally, the long-term toolkit does not impact flies' behaviors compared to intact flies and can be used to image both sparse and large populations of neural activity in flies' cervical connective and VNC. The toolkit was tested in two proof-of-concept (POC) applications. In the first POC, the toolkit monitored the degradation of sensory neurons in the VNC over weeks following limb amputation. In the second POC, the toolkit monitored global changes in neural dynamics following ingestion of a high-concentration caffeine solution. In conclusion, this thesis introduces new techniques for functional recordings of the fly's cervical connective and VNC over short and long time scales. They enable optical access to the fly's cervical connective that can be leveraged to study the content of information transmitted between the brain and the VNC while the fly is behaving. The two POCs demonstrate that the novel technology is ideally suited for long-term experiments and could be applied to a wide range of studies. For instance, the toolkit could be used to investigate how behaviors are encoded in the fly's VNC and how they adapt over time to experiences such as disease, aging, drug intake and learning.

EPFL2022

Uncovering the neural substrates of communication between the brain and ventral nerve cord in Drosophila melanogaster (italic)

Florian Aymanns

Despite a long history of research in motor control, the exact mechanism of how the brain communicates with the the invertebrate ventral nerve cord (VNC) and the vertebrate spinal cord on a single neuron basis remains largely elusive.Drosophila melanogaster is an ideal model organism to address the role of individual neurons, thanks to its stereotyped nervous system.Descending neurons (DNs), interneurons in the brain that project to the invertebrate ventral nerve cord or vertebrate spinal cord, have been shown to elicit specific behaviors upon optogenetic activation in Drosophila.These results suggest that behavior is controlled by sparse sets of command neurons, each eliciting a particular behavior.However, it remains to be seen how many DNs are involved in the control of naturalistic behaviors and what other information they might encode.In order to avoid commands leading to physically impossible or destabilizing actions, the brain has to be aware of the current behavior state.Ascending neurons (ANs), interneurons in the invertebrate ventral nerve cord or vertebrate spinal cord projecting to the brain, are likely conveying this information to the brain.To which degree of fidelity and in what way ANs encode behavior state remains unclear.To address these questions, we developed a dissection approach that allows functional imaging of ANs and DNs in the cervical connective.This dissection gives us optical access to the cervical connective and parts of the VNC in behaving adult Drosophila such that a two-photon fluorescence microscope can be used to image neural activity via calcium indicators.We began by imaging a new library of sparse split GAL4 driver lines targeting ANs.Our recordings from 247 genetically identifiable ANs revealed neurons encoding walking, resting, turning, eye grooming, and foreleg movements.Anatomical characterization of these ANs showed that they predominantly project to two brain regions: the anterior ventrolateral protocerebrum (AVLP) and the gnathal ganglion (GNG).Our results suggest that ANs encoding the motion of the animal with respect to the surrounding environment (self-motion) predominantly project to the AVLP, an integrative sensory hub. ANs projecting to the GNG mostly encode discrete actions.We then proceeded to image populations of DNs.The majority of DNs we recorded encoded walking behavior, with smaller fractions encoding resting and head grooming.Some of these neurons are likely to drive walking, but we also identified neurons encoding walking speed and turning.This suggests that a core set of DNs drives a behavior whose features can be modulated by additional DNs.Besides encoding behaviors, some DNs encode sensory information, including the presence of odors and deflection of the antennae.

EPFL2022

Methods for acute and long-term imaging of the ventral nerve cord in behaving adult Drosophila

Laura Joan Hermans

EPFL2022

Uncovering the neural substrates of communication between the brain and ventral nerve cord in Drosophila melanogaster (italic)

Florian Aymanns

EPFL2022