Cooperative Agreements

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.

ABSTRACT Perceptual decision-making is a fundamental cognitive ability that is vital to healthy, daily functioning and is impaired in many diseases. Although many brain regions are known to be involved, there is no clear brain-wide model of how perceptual decisions are formed and executed and the underlying circuit mechanisms are still largely unknown.

Classical conditioning has been studied in many different animal models, and even in humans. However, the larval zebrafish with its transparent brain offers a unique opportunity to observe large scale changes in synaptic structure that accompany this form of learning. Accordingly, we have developed a novel paradigm for visualizing synaptic changes that occur during classical conditioning in larval zebrafish. Using this paradigm we have observed striking region-specific changes in the distributions of synapses that drive the rewiring of neural circuits that mediate threat responses.

Abstract: Attachment powerfully shapes our development and remains a primary driver of health and well-being in adulthood; disruption of attachments is highly traumatic. While affiliation, defined as general positive social interactions, is shared widely among mammals, attachment, or selective affiliation as a result of a bond, is far rarer and of primary relevance to humans. While affiliation has been studied in a number of contexts, how the neural circuitry that underlies affiliation ultimately contributes to adult attachment remains largely unknown.

Project Summary This proposal explores an emergent computational framework for understanding the neural population codes that support flexible, context-dependent behavior. The current state of the field is based on two competing views. According to the circuits view, fixed behaviors arise from specific anatomically or genetically defined cell populations that serve specific functions. Alternatively, the network computation view instead holds that neural activity provides mixed representations of task variables and can be understood only based on the joint activation of many neurons.