Jayaraman Lab

Research

We are interested in understanding the neural computations underlying sensory-motor transformation and multi-sensory integration in a simple system. How is information from single and multiple sensory streams processed in the brain to enable an organism to produce appropriate motor responses? What cellular and network mechanisms underlie behavioral changes in response to reward and punishment associated with some sensory-motor decisions? We believe that exploring such issues requires studying neural activity in a behaving organism. Furthermore, validating any potential answers requires manipulating neural circuits in precise and well-controlled ways. This leads us to our experimental system, the fruit fly (or, more accurately, the vinegar fly), Drosophila melanogaster, which has long been the organism of choice for behavioral genetics and comes with tools to fluorescently label, manipulate the activity of, and optically record from genetically targeted neurons.

FlyOnBall DIC Image PB cell-attached recording GCaMP Neurons

We use electrophysiology and two-photon imaging (often simultaneously) to record from brain neurons in a head-fixed adult fly while it walks in place on a tiny ball. For electrophysiology, we use visually guided whole-cell patch clamp and cell-attached techniques to record from labeled neurons. We are also trying to develop extracellular methods to record from identified neural ensembles. For optical imaging, we mainly use recently developed genetically encoded sensors (of, for example, calcium), some of which are developed by Loren Looger's lab. The advantage of such sensors is that the same genetically identified neurons can be targeted for imaging in fly after fly. Although these sensors currently lack the temporal resolution to monitor neural activity with single-spike resolution in vivo, they can nonetheless be used to identify foci of interest for more-refined recordings using electrophysiological techniques. We work in close collaboration with Michael Reiser's group who have considerable expertise with Drosophila behavior. With this combination of electrophysiological and optical recordings, quantitative behavior, and a variety of computational techniques, we are exploring how sensory information is transformed into motor output in the tethered fly's brain.

Two broad and related lines of research in our lab concern:

Identification of neurons and circuits in the fly brain involved in multisensory integration and sensorimotor transformations. This effort involves using genetic, electrophysiological, imaging and behavioral techniques to establish functional connectivity and to map circuits of interest. Circuit mapping and functional connectivity is also an interest of our collaborators in Julie Simpson's lab, and we work with them to test reagents to manipulate and record neural activity. Our main focus is on an intriguing structure of the fly brain called the central complex. This structure, which is found in all insects, consists of four interconnected and stereotypical neuropillar sub-regions. Based mainly on data from behavioral genetics experiments, the central complex is thought to subserve multi-sensory and sensorimotor functions. We are hoping to elucidate the workings of this deep area of the brain further by adding physiology to the mix.
Neural processing of sensory-motor information. In collaboration with Michael Reiser's lab and Janelia's Instrumentation Design & Fabrication group, we are developing techniques to perform electrophysiological and optical recordings in a tethered, behaving fly that is walking on an air-supported ball inside a visual-olfactory arena. The movement of the ball is tracked with high fidelity and temporal resolution, allowing us to infer the fly's intended movements. We are beginning to use this setup to correlate neural activity with both the sensory information presented to the fly and its motor output. We hope that proceeding systematically in this manner will allow us to better understand computations carried out by neurons in different parts of the central complex during ethologically relevant behavioral paradigms. We are able to target different sub-regions of the central complex by taking advantage of the highly restrictive expression patterns of selected Gal4 lines, many of which are generated and catalogued locally in Gerry Rubin's lab. Computational analysis and modeling are also key components of our effort to uncover the function of this circuit.

Establishing causal links between multimodal computations of neuronal ensembles and the fly's online decision-making behavior is a long-term goal for our lab. Along the way, we hope to discover some general principles about sensory-motor representations, neural computation, and the functional organization of small circuits.

Jayaraman Lab: Research

Research