Research Projects

Project Summary/ Abstract Multiphoton, depth sectioning micro-endoscopes are of paramount importance in capturing neural activity with cellular resolution. Imaging speed and the field-of-view in the current two-photon endoscopes has remained limited by the resonant scanning devices that are required at the distal end. Temporal focusing is multi-photon imaging technology which has enabled wide-field, scan-free, two-photon microscopy at over 200 frames per second.

ABSTRACT Optical imaging holds tremendous promise in our endeavor to understand brain functions. The major challenges for optical brain imaging are depth and speed. Due to strong tissue scattering, the penetration depth and imaging speed of optical microscopy in the mouse brain is very limited. These constraints in depth and speed make large scale, volumetric imaging of mouse brain activity, e.g., functional imaging of an entire mouse cortical column, out of reach of current imaging techniques.

Measuring and understanding the activity of individual neurons is critical for understanding how neuronal circuits function and lead to behavior. Two-photon microscopy of calcium-sensitive indicators has produced insightful data on the role of individual neurons with populations. With the use of head-fixed or miniaturized versions, such optical techniques have lead to links between neural dynamics and behavior. However, these methods have not translated to voltage indicators, so that the understanding of how spikes across populations of cells affects circuits and behavior is lacking.

Today’s knowledge of large-scale neural networks is advancing along two orthogonal directions. Spatial (static, structural) connectomic understanding is achieved through optical and electron microscopy; yielding high spatial resolution with limited or no temporal information. Conversely, electrophysiological methods provide an exceptional temporal understanding of millisecond-order neurodynamic activities in vivo, with restrictions placed on spatial information. Unfortunately, these approaches have historically been rather mutually exclusive and incompatible with each other.

Fluidic Microdrives for Minimally Invasive Implantation and Actuation of Flexible Neural Electrodes Abstract Flexible microelectrodes that match the mechanical properties of the brain promise to increase the quality and longevity of neural recordings by reducing chronic inflammatory reactions; however, these microelectrodes are traditionally difficult to implant without causing acute damage.

Project Summary Neuromodulators play an important role in our life by dynamically adapting the brain to an ever-changing environment. By simultaneously activating multiple receptor classes that are distributed amongst distinct components of neural circuits, neuromodulators can effectively rewire the brain in a reversible manner. However, the involvement of specific neuromodulators in distinct cognitive processes has been difficult to establish.

Project Summary: Decoding the electrical and chemical signals in neural circuits is essential to understand the communication between different brain regions and how these neural networks give rise to a particular function at the level of the whole organism. Therefore, recording or modulating neural activity with high spatiotemporal resolution is necessary. Ideally it is desired to achieve this noninvasively for long-term translation of these technologies to behaving animals and eventually to humans.

A major focus of modern neuroscience is understanding the role of neuromodulators in neural circuit function and development, in behavior, and their dysfunction in neurological disease. Neural circuit research has been revolutionized by powerful new optical techniques. Here we propose to use new near-infrared optical nanosensor technology to image dopamine. As a proof of principle, we will use this sensor to monitor dopamine release under physiological conditions in both the developing and adult retinas.

Rigneault Project Abstract DEEPHIPPO DEEPHIPPO: Ultra‐thin lensless endoscope for the visualization of deep hippocampus neuronal functional activity. Principal investigator: Hervé Rigneault Host Institution: Aix‐Marseille University, Marseille, France Project duration : 24 months Project Abstract DEEPHIPPO breaks the experimental limitations of in vivo two‐photon calcium imaging in the deep brain where multiphoton (2photon and 3photon) microscopy is impossible.

Project Summary The ability to trigger neural activity with high resolution millimeters to centimeters deep in tissue remains an elusive goal in neuroscience research. Current research relies on using invasive electrodes, optogenetics, or pharmacological stimulation. None of these technologies, however, is capable of providing large-scale neural stimulation with high spatial resolution. In this project, we propose to combine piezoelectric barium titanate nanoparticles with ultrasound excitation to trigger neural activity.