Theory & Data Analysis Tools

Abstract Optical recordings of activity are critical to probe neural systems because they provide high-resolution, non-invasive measurements, ranging from single neurons to entire populations in intact nervous systems, and are readily combined with genetic methods to provide cell type-specific recordings. Nevertheless, the limited penetration depth, spatial scale and temporal resolution remain major challenges for optical imaging. Cellular- resolution imaging in scattering brains is typically achieved with multiphoton microscopy (MPM).

Abstract: Single-photon (1P) epifluorescence miniaturized microscopy coupled with genetically encoded calcium sensors has allowed investigators to record the activity of large populations of identified neurons over days to weeks in freely behaving animals, answering fundamental questions in neuroscience. Our group's efforts with the UCLA Miniscope Project have allowed over 600 labs to build and use over 2500 open-source miniaturized microscopes with expanded capabilities at a small fraction of the cost of those offered by commercial versions, thus democratizing access.

PROJECT SUMMARY Understanding how information is processed in the mammalian neocortex has been a longstanding question in neuroscience. While the action potential is the fundamental bit of information, how these spikes encode representations and drive behavior remains unclear. In order to adequately address this problem, it has become apparent that experiments are needed in which activity from large numbers of neurons can be measured in a detailed and comprehensive manner across multiple timescales. Direct measurements of action potentials have primarily been achieved by electrophysiology.

The goal of this project is to provide the building blocks for an independent research program focused on the mechanisms by which neural networks incorporate multisensory cues into episodic memories. Discrimination of different contexts composed of distinct constellations of multisensory cues is a hallmark of both episodic memory and spatial navigation, two functions ascribed to the mammalian hippocampus.

Project Summary Electrical microstimulation has become a mainstay of fundamental neuroscience exploration and an increasingly prevalent clinical therapy. Despite the growing prevalence of neuromodulation therapies, the fundamental physiological and mechanistic properties driving the beneficial effect for the patient are poorly understood. This R01 application aims to greatly improve our understanding of how different non-neuronal cells (myeloid lineage, oligodendrocyte progenitor lineage, and vascular smooth muscle cells) respond and contribute to the electrical stimulation response.

Project Abstract The application of electric stimulation (ES) to the brain has been widely used to perturb the physiological and pathological dynamics of neuronal circuits, with established applications including therapeutic interventions for neurological disorders such as epilepsy, dementia, and Parkinson’s disease. However, the biophysical mechanisms underlying ES in the brain remain unclear. There is still a lack of understanding about where, when, and how to apply ES to brain circuits in vivo.

Project Summary Intracranial electrical brain stimulation (EBS) remains a central method in the clinic as well as for research in several animal model systems. However, little is actually known about the ensembles of neurons activated by typical and clinical intracranial EBS protocols. These stimulation protocols often require a trial-and-error learning period (during and after invasive neurosurgery) to determine what stimulation parameters are effective, if any at all are effective.

Abstract: Our goal is to develop a cellular level understanding of how transcranial magnetic stimulation (TMS) may activate neurons in the human cerebellum (Cb) using (i) electrophysiological measurements in an in vitro turtle Cb, (ii) computational modeling of the induced electric (E) fields in the tissue and (iii) an MEG-EEG-TMS human saccade study. Since the local microanatomy and electrophysiology of the Cb are evolutionarily conserved from reptiles to man, it is likely that the fundamental neural dynamics will generalize.

Project Summary Transcranial current stimulation (TCS) creates small electrical fields in the brain through electrodes placed on the scalp. As a method for neuromodulation, TCS carries with it many practical benefits: it is portable (battery- operated), inexpensive, and easily deployable in the clinic and at home.

Cell Type and Circuit Mechanisms of Non-Invasive Brain Stimulation by Sensory Entrainment Patterned sensory stimulation (PSS) is a non-invasive technique for manipulating brain activity and states, typically employing periodic light flicker or auditory tones presented at regular intervals.