Understanding Circuits

PROJECT SUMMARY/ABSTRACT Many animals rely on spatial cognition for daily survival in order to recognize familiar places and process movements through or between locations. A variety of space-encoding cells in the hippocampus are important for spatial behaviors in mammals. However, neural encoding of space remains uncharacterized in other vertebrate taxa, including amphibians, whose simpler brain structure suggests alternative mechanisms of encoding space.

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.

Project Summary: Memory enables animals to acquire, store, and recall knowledge of the world through experience and use this knowledge to maximize reward and avoid danger. Understanding the circuit mechanisms within and between brain regions that underlie the formation and recall of memories is considered one of the great scientific challenges of our time, and has the potential to drastically influence the treatment of memory disorders. The hippocampus is both necessary and sufficient for the formation and recall of episodic memories—memories of experiences placed in time and space.

PROJECT SUMMARY/ABSTRACT When learning in complex, realistic, or even real worlds, we have the benefit of using different strategies adaptively. For most primate brains, adaptive means adjusting as a function of where we are, who we are with, and what things of use are in view or in reach. Learning theories like Complementary Learning Systems (CLS) originally suggested that the hippocampus and neocortical structures contributed distinct computations to represent different kinds of memory.

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.