Understanding Circuits

State-dependent modulation of taste and temperature integration in Drosophila

PROJECT SUMMARY: Animals constantly detect different environmental stimuli and change their behavior or physiology based on their internal state. How animals integrate the external multiple sensory information with the internal state is largely unclear. The specific goal of this proposal is to explore the neural circuits and mechanisms of internal state- dependent modulation of multiple sensory integrations. We will draw on a powerful, versatile, and relatively simple genetic model, Drosophila, to address the neural mechanisms of taste-temperature integration.

Pre-motor neural circuits enable versatile and sequential limb movements

Abstract Movements are measurable outputs of the nervous system and simple movements can be combined to compose complicated behaviors. We use limb tracking and connectome analyses to map the neural circuits controlling the elemental leg movements in Drosophila grooming. The organization of the pre-motor networks for this innate, sequential behavior will show a successful solution for a complex motor control problem and reveal generalizable connectivity motifs whose computational functions can be experimentally tested.

Cortical circuit dynamics underlying multisensory decision making

Project Summary To navigate and guide locomotion in a complex 3D environment, humans and animals must make countless judgments of their direction of self-motion, or heading. Each of these is a multisensory perceptual decision, able to achieve greater accuracy and precision by combining signals from the visual, vestibular, and kinesthetic senses. At the same time, the brain must decide when to commit to a course of action (e.g., to quickly change direction to avoid an obstacle), and make predictions of the likelihood of success in that action.

Neural circuits for social modulation of a persistent negative emotional state

PROJECT SUMMARY In social species, social relationships can exert profound influences on individuals’ behavioral and physiological states. In particular, social interactions can help reduce negative emotional state induced by physical or psychological stressors, a phenomenon known as social buffering. Social buffering provides an important means by which the social environment facilitates stress coping and resilience and benefits health and well-being.

Role of coordinated multi-area reactivations during transitions between automatic and flexible behaviors.

Abstract Sleep occupies a large part of our lives and is widely believed to perform essential functions. During sleep, the neuronal rules of engagement and population dynamics are clearly different than waking. There is extensive evidence that one primary function of sleep is to consolidate memories formed during waking. Recent work, however, suggests that sleep may also actively alter neural connections to achieve forgetting (‘unlearning’). How the brain balances learning and forgetting, exactly how sleep contributes, and the ultimate effects on ensembles and behavior are unknown.

Peptidergic neurons in error computations and behavioral flexibility

PROJECT SUMMARY Survival in dynamic environments demands that behaviors are flexible and adaptive. An organism must make predictions about which actions lead to rewards, calculate how outcomes differ from those predictions (prediction errors), and adapt a behavioral strategy accordingly. Neurons encoding prediction errors can be found throughout many reward-related brain structures, with the highest densities in the VTA and the lateral habenula (LHb).

Next Generation Opto-GPCRs for Neuromodulatory Control

Project Summary/Abstract: The field of optogenetics — utilizing light to engage biological systems — is widely used for the dissection of neural circuits, cellular signaling and manipulating neurophysiological systems in awake, behaving animals. However, while many new opsins have been developed and are actively used, challenges still remain, and the current technology lacks a full toolbox for sub-cellular, spatiotemporal control of signaling — the predominant means for neuromodulator communication in the brain.

Multiplex Imaging of Brain Activity and Plasticity with Optimized FRET/FLIM-based Sensors

Project Summary Plasticity is a fundamental aspect of neuronal circuits across all species. It is at the base of learning and memory, sensory adaption, and many disease-related processes such as addiction, chronic pain or regeneration. On the molecular level biochemical mechanisms have been well described, but little is known on how these are coordinated in space and time within neuronal circuits of living brains.

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