Marco Gallio - US grants

DESCRIPTION (provided by applicant): Our long term goal is to provide a framework to understand how a simple, innate behavior emerges from the activity of the nervous system. For this, we will apply a battery of molecular genetics techniques and imaging technologies to study the circuit mechanisms underlying temperature preference in Drosophila -a system ideally suited for a comprehensive genetic and molecular dissection of neural circuits and behaviors. We have recently shown that temperature is represented by a map of activity created by sensory afferents at the first relay station in the fly brain. We now propose to study how this map is processed by central neural circuits and transformed into directed behavior. To accomplish our overall objectives, we will use a combination of targeted photo-activation of GFP, GRASP, ChR2-mediated circuit mapping and genetic expression of effector molecules to: 1) Identify ascending neuronal populations receiving temperature information and representing it to higher brain centers. 2) Study their tuning and properties, and narrow our search to the key pathways that mediate temperature navigation and preference. 3) Determine their connectivity to higher brain centers, study the transformation of stimuli at each station in the circuit and eventually track the descending pathways that control behavior. This work is expected to contribute to our general understanding of the wiring logic of the neural circuits that control innate behavior in animals, and potentially provide insights on how genetic conditions which affect wiring can result in compromised circuit function and altered behavior.

PROJECT SUMMARY: The long term goal is to provide a framework to understand how a simple, innate behavior emerges from the activity of the nervous system. For this, molecular genetics techniques, electrophysiology and imaging technologies to study the mechanisms underlying temperature processing and preference in Drosophila -a system ideally suited for a comprehensive genetic and molecular dissection of neural circuits and behaviors, are applied. The lab's recent work has demonstrated that a simple sensory map represents temperature stimuli in the fly brain. It has also shown that a coordinated ensemble of second order neurons extracts information about the sign, onset, magnitude and duration of a temperature change from this simple map. The research is now proposing to delve deeper into the cellular and molecular mechanism that make this transformation possible. The expectation is that the results of this work will reveal new mechanisms and principles of somatosensory processing in the nervous system, will complement discoveries on differential feature extraction in other sensory modalities, and will have implications of interest to the broader neuroscience community, informing work on information processing within neural circuits. This work is also expected to contribute to the general understanding of the function of the neural circuits that control somatosensory responses (temperature and pain) in animals, potentially providing insights on genetic and neurological conditions which affect neuronal excitability resulting in devastating medical conditions such as chronic pain.

PROJECT SUMMARY Understanding how our brain's 100 billion neurons process information to produce complex feelings, decisions, and behaviors is a daunting task. A single neuron in the human brain may communicate with more than a hundred thousand partners. For each partner, this exchange happens at multiple specialized contact sites called synapses. Genetic studies are now revealing that mutations that alter the formation or activity of synapses are often at the root of neurological conditions ranging from autism spectrum disorder to epilepsy. Here, we will develop a new, revolutionary technology that will allow us for the first time to re-engineer connectivity in the living brain, preventing the formation of specific synaptic contacts between neurons to test specific hypotheses on circuit dynamics and behavior. Our strategies are completely non-invasive (as they depend on genetic reagents), can be applied on large scale, and can be used to manipulate/modulate neural activity directly in behaving animals. We will initially develop our reagents for use in Drosophila, but we anticipate that our strategies will be immediately applicable to any animal model system (zebrafish, rodents, etc.). This work will expand our mechanistic understanding of how brain circuits function in the normal state, as well as allow the design of new experiments that accurately reproduce synaptic dysfunctions known to underlie human disease.