1998 — 2010 |
Krauzlis, Richard J |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Coordination of Voluntary Eye Movements @ Salk Institute For Biological Studies
DESCRIPTION: (Adapted From The Applicant's Abstract) The long-range goal is to understand how the neural mechanisms for pursuit and saccadic eye movements operate in health and in various human disease states and how these mechanisms are related to visual perception. Recently, we have obtained behavioral and electrophysiological data indicating that there is functional overlap between the neural mechanisms for pursuit and saccades. The objective of this application is to investigate the nature and degree of this functional overlap In particular, we will determine how the rostral superior colliculus and one of its primary targets, the paramedian pontine reticular formation, participate in the control of pursuit, as well as saccades. This proposal tests two main hypotheses. First, that some neurons in the rostral superior colliculus encode the retinal locations of possible targets, rather than specific commands for eye movements. Second, that the decision to make a saccade or pursuit or no eye movement occurs downstream. The project will address the following three questions: (1) What types of information are encoded by neurons in the rostral superior colliculus that could be used to guide both pursuit and saccades? (2) Is activity in the rostral colliculus selective for the location of the target or the type of eye movement that the subject makes? (3) Could activity in the paramedian pontine reticular formation provide part of the command for pursuit or determine which type of eye movement is made? At the completion of this research, we expect to understand how activity in the rostral superior colliculus is related to the mechanisms of both target and eye movement selection, and to have a preliminary understanding of how activity in the paramedian pontine reticular formation contributes to the control of pursuit. These studies are a step toward understanding how the brain coordinates the components of voluntary movements and how it establishes and regulates the line between visual processing and movement selection. These studies will therefore help refine clinical descriptions of the oculomotor system that are used to diagnose eye movement disorders in humans.
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0.922 |
2011 — 2012 |
Callaway, Edward M (co-PI) [⬀] Krauzlis, Richard J Reynolds, John H [⬀] |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Optogenetic Tools to Selectively Activate Projection Neurons in Awake Primate @ Salk Institute For Biological Studies
DESCRIPTION (provided by applicant): Our understanding of the neural mechanisms underlying action, perception and cognition has been limited by the lack of tools to modulate the activity of specific neural circuits in the awake, behaving animal. This technical hurdle has, in turn, limited our understanding of devastating disorders of the nervous system that result from dysfunction of neural circuits. The proposed research addresses this challenge by developing a new set of optogenetic techniques that will make it possible to selectively manipulate the activity of projection neurons with precise temporal control in the brain of the behaving non-human primate. We plan to inject viral vectors, specifically designed to be taken up by axon terminals, into the brain in order to get projection neurons to express the light-sensitive channels channelrhodopsin-2 and archaerhodopsin-3. We will then be able to selectively activate or inactivate projection neurons using light introduced into the brain with specially designed optitrodes. Our proposal focuses on projections from primary visual cortex (V1) to the superficial layers of the superior colliculus and V1 neurons projecting to the secondary visual area (V2), taking advantage of the well- defined retinotopic maps in these regions, and using physiological, behavioral, and histological methods to measure our ability to selectively manipulate the activity of projection neurons. The results of these studies are likely to have a large impact, because the tools and techniques developed in this research program will have wide applicability for those studying the relationships between functional neural networks in the CNS and primate behavior. They will also provide important tests of the feasibility of optical and virus-based methods as possible therapeutic approaches in CNS disorders. PUBLIC HEALTH RELEVANCE: Understanding the functional role of particular neural connections is crucial for unraveling the etiology of neuropsychological disorders such as neglect, Balint's syndrome, visual agnosia, schizophrenia, ADHD and autism. The goal of this project is to establish new techniques for selectively manipulating the activity of projection neurons in the behaving non-human primate under precise temporal control using combinations of physiological, molecular, and genetic methods. The results from our studies will demonstrate powerful new tools for studying the functional relationships between neural networks and primate behavior, and provide important tests of the feasibility of optical and virus-based methods as possible therapeutic approaches in CNS disorders.
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0.922 |