Monitor Neural Activity

How are complex behaviors that require the coordination of multiple muscle systems produced? How does the brain suddenly turn them “on”? Vocalizations are seemingly simple, yet to occur, ~100 muscles must be coordinated, such as those for articulation (laryngeal and tongue) and breathing. Moreover, vocalizations must seamlessly integrate with or perhaps even override the breathing rhythm. Innate vocalizations occur in multiple behavioral contexts, like mating, and are presumed to be initiated by a gatekeeper, the periaqueductal gray (PAG).

This proposal will investigate neural circuits driving negative phototaxis in an emerging model for neural circuit analysis: larvae of the primitive chordate Ciona. Ciona larvae have a number of features that make them ideally suited for this project. They are small and transparent, and have only 177 CNS neurons. Moreover, putative circuits for phototaxis have been identified from the Ciona connectome. Negative phototaxis in Ciona larvae consists of two phases.

Project Summary Primary motor cortex (M1) and the locus ceruleus (LC) both contribute in essential ways to the generation of purposive movements – with M1 and its pyramidal tract (PT) neurons involved in action planning and execution, the and LC and its noradrenergic axonal projections involved in aspects relating to arousal and attention. The cellular- and circuit-level mechanisms by which these two major brain systems communicate and interact are not well understood.

Cognitive decline begins in early stages of Parkinson’s disease (PD) and progresses to dementia in 75% of people with PD after ten years. Dopaminergic medication and deep brain stimulation (DBS) provide long-term improvement of cardinal motor symptoms in PD, but cognitive decline remains largely unaddressed and untreated, despite a long window for potential intervention before dementia occurs.

SUMMARY Motivation: In the US, almost 800’000 people have a stroke every year. Unfortunately, despite intense physio- therapy stroke survivors retain permanent arm motor deficits, some complete hemiparesis.

Project Summary/Abstract Neurological and psychiatric disorders affect millions of people in the United States and worldwide, and produce a third of all health care costs. Recent research has produced encouraging evidence that adaptive neuromodulation can induce nervous system plasticity that produces long-lasting improvements in certain neurological disorders such as stroke.

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 neural circuits of animals, including humans, are the combined product of adaptation by natural selection and the evolutionary history of a species. Distinguishing which features of neural circuits represent fundamental principles of circuit design versus the quirks of a particular model species requires comparative approaches. Features of neural circuit design and architecture that have evolved independently multiple times in distantly related species indicate elements of optimal solutions to solving a particular behavioral or cognitive problem.