Neural mechanisms enabling context-dependent sensorimotor flexibility

• Applicant: Dr. Jan M. Ache
• Subject Area: Cognitive, Systems and Behavioural Neurobiology ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 433646517

To ensure survival in an ever-changing, complex world, animal behavior needs to be flexible and adaptive. Nervous systems have evolved to enable behavioral responses to a wide variety of sensory stimuli, but the adequate behavioral response to a given stimulus is highly context-dependent, and behavioral or internal states accordingly affect sensorimotor processing. For example, locomotion modulates responses of visual neurons, and hunger increases food-searching behavior and shifts taste preferences. Despite their ubiquitous importance, the neural mechanisms enabling context-dependent sensorimotor flexibility are not well understood. My research program aims to discover fundamental principles of motor control, in particular with regard to sensorimotor flexibility, by leveraging the power of neurogenetics, electron microscopy-based circuit reconstruction, and in-vivo patch-clamp recordings in behaving Drosophila.While the brain performs large parts of sensory processing and motor planning, the actual motor output is primarily generated by circuits in the ventral nerve cord (VNC, the insect analogue of the spinal cord). In Drosophila, the only connection between the brain and VNC is formed by a population of only approximately 400 descending neuron (DN) pairs, which thus constitute an information bottleneck. Due to their unique role of linking the brain to the VNC, their individual identifiability, their small number, and their ability to drive and control specific actions, DNs are an ideal substrate to investigate fundamental principles of flexible motor control.My research program aims to unravel how sensory networks of the brain are flexibly coupled to motor networks of the VNC by the context-dependent modulation of identified, action-specific DNs. First, I will focus on the effects of behavioral states, such as quiescence, walking or flight, on DN activity. Changes in behavioral state also affect metabolism and vice versa, since flight, for example, is particularly energy-demanding. Therefore, I intend to unravel the neural mechanisms via which metabolic and behavioral states interact. My research objectives encompass five questions. Answering them will 1) Establish whether gating and modulation of DNs is a general mechanism underlying context-dependent sensorimotor flexibility; 2) Identify the neuronal mechanisms underlying the differential, context-dependent modulation of individual DNs; 3) Elucidate where and how context-dependent action-selection occurs in sensorimotor pathways by leveraging the discovery of a microcircuit controlling escape and landing responses; 4) Quantify and model the context-dependent activity of a population of insulin producing cells in the brain as a proxy for insulin release dynamics; and 5) Reveal how the concerted interactions of insulin and octopamine (the insect analogue of adrenaline) integrate behavioral and metabolic state information to achieve the context-dependent modulation of sensorimotor circuits.

• DFG Programme: Independent Junior Research Groups
• Major Instrumentation: Patch-clamp setup
• Instrumentation Group: 5040 Spezielle Mikroskope (außer 500-503)