Michael Rowe - US grants

The mammalian retinal ganglion cell population comprises a number of functionally distinct groups of neurons giving rise to a number of parallel information channels in the optic nerve which have proven to be of considerable importance in the organization of central visual pathways. Nevertheless, knowledge of the cellular interactions underlying the formation of these channels is largely incomplete. Furthermore, the retina is susceptible to damage from a variety of diseases and systemic disorders, most of which are poorly understood. Knowledge of how retinal neurons interact is essential for a complete understanding of how these diseases affect retinal tissue, and for the development of effective diagnostic as well as therapeutic procedures. This proposal is to do an intracellular analysis of the responses and receptive field properties of ganglion cells and other retinal neurons in the intact eye of the cat. Such as analysis will: (1) allow the synaptic inputs of functionally distinct types of ganglion cell to be identified; (2) allow the complex receptive field properties of non-spiking retinal neurons to be studied under natural optical conditions, and with the same stimuli used to study ganglion cell receptive fields; (3) allow a direct comparison to be made between the response properties of the ganglion cells and those of other retinal neurons to identical visual stimuli; (4) contribute to our understanding of the mechanisms and circuitry underlying the formation of the functionally distinct, parallel information channels which are a major organizational feature of the central visual pathways.

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The mammalian retinal ganglion cell population comprises a number of functionally distinct groups of neuronrther been shown to be anatomically segregated as they course through the optic tract. In cats, a heterogeneous mixture of ganglion cells, often collectively referred to as W-cells, make up about 50% of the total population. Nevertheless, their receptive field properties have not been thoroughly analyzed and are not fully undestood. Consequently, we have littel understanding of their role in visual information processing, and are not yet able to explore the mechanisms underlying their response characteristics. Such knowledge is vital, however, in order to fully understand how various retinal perception, and will be important for the development of effective diagnostic and thereapeutic procedures. This proposal is to do a thorough and quantitative analysis of he receptive field components of W-cells in the cat retina in vivo, using the method of spatial frequency analysis. Specifically, these experiments will: (1) identify and characterize the receptive field components of retinal W-cells in terms which will allow direct comparisons with X- and Y-cells; (2) make it possible to analyze the complex visual behavior of these cells in terms of interactions amng well defined receptive field components; (3) provide a basis for understanding the role of W-cells in visual information processing and visual perception; (4) provide a basis for exploring the cellular and synaptic mechanisms underlying receptive field formation in W-cells.

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In spite of several decades of intensive study, many prominent features of the physiology of visual cortex have not been fully elucidated. Among these are 1) the precise mapping of different retinal ganglion cell classes onto the diversity of cortical areas, layers and cell types, and 2) the mechanisms by which retinal signals are converge onto cortical cells so as to produce emergent properties such as orientation selectivity. In this proposal, we present a new method which permits direct exploration of these and other issues. We plan to record simultaneously from cortical cells and retinal ganglion cells with overlapping receptive fields, and by means of cross-correlating their spike trains, to identify the specific retinal inputs to cortical cells. By systematically mapping multiple retinal inputs to single cortical cells, we can test hypotheses about the contributions that these inputs make to cortical cell receptive field structure and properties. We can also compare the spatial and temporal tuning characteristics of cortical cells with that of their inputs, and can identify the contributions that X, Y, and W cells make to the functional attributes of cortical areas 17, 18, and 19 and their constituent cell types. These results will greatly expand our understanding of information processing in the visual system, and will establish a foundation upon which to understand the functions of intrinsic cortical circuits.

DESCRIPTION (provided by applicant): Over the past 40 years, considerable progress has been made in understanding mechanisms of vestibular function. One major advance has been the recognition that vestibular primary afferents are structurally and physiologically heterogeneous; unfortunately, the functional significance of this diversity remains unclear. A central issue is the fate of afferent signals when they reach the CNS: how do different afferents modulate the activity of central vestibular neurons, and how do these effects depend on the nature of the stimulus? I propose to address this question through simultaneous extracellular recordings from (1) single vestibular nucleus neurons and (2) their eighth nerve afferents in an in vitro preparation of the turtle brainstem. Dynamic afferent stimulation will be provided by sinusoidally modulated currents delivered to the posterior canal. This approach will allow me to: 1) quantify the contribution of individual vestibular afferents to the discharge of secondary neurons; 2) quantify patterns of convergence of vestibular afferents with different functional properties onto individual secondary neurons; 3) quantify the dynamics of signal transmission across the synapse and any changes that occur as a function of stimulus properties. This R21 application seeks funding to establish the feasibility of my dual recording preparation and to conduct pilot studies on synaptic transmission at the first central vestibular synapse. Once these aims are accomplished I will be positioned to pursue my long-term objective: to learn how synaptic transmission between afferents and vestibular nucleus neurons varies as a function of afferent type and the nature of the afferent stimulus.

Recent models of rifting in the Southwest United States have suggested that the mantle beneath the North American Plate has undergone hydration, potentially from shallow subduction of the Farallon Plate beneath the North American Plate from ~80-40 million years ago. The addition of water and other volatile elements (chlorine, sulfur, fluorine) to the continental mantle (lithosphere) may have a profound influence on volcanism and tectonic processes. Water (along with volatile and fluid-mobile trace elements) added to the mantle reduces the melting temperature, allowing magmas to be generated at lower temperatures. Additionally, hydration of the mantle weakens the lithosphere, potentially allowing for a greater extent of rifting. Despite the clear significance of hydration of the mantle, direct constraints on the amount of water in the lithosphere or the source(s) of this water are few. The primary focus of this research therefore is to measure volatile abundances in basaltic lavas to determine the extent to which volatiles have been added to the continental lithosphere. This study will concentrate on the Rio Grande Rift in New Mexico- the extent of rifting varies from N-S making this an ideal location to test for a correlation between hydration of the lithosphere and the extent of rifting and volcanism.

Because magmas degas upon eruption on the Earth's surface, precise measurements of volatile abundances can be problematic. In order to address this dilemma, melt inclusions, small parcels of magma trapped within minerals during crystallization and prior to degassing, will be analyzed to provide constraints on the volatile content of primitive basaltic magmas. Primitive lavas will be collected for this study from N-S and E-W transects along and across the Rio Grande Rift to adequately compare volatile concentrations to the extent of rifting and to look for lateral variations in the degree of mantle hydration. Additionally, lavas of varying ages will be examined to address potential temporal variations in the hydration of the lithosphere and potential transition from lithospheric to asthenospheric mantle melting. Despite prior evidence of enrichment in fluid-mobile trace elements (e.g., high Ba/Nb and Sr/Nd), the source of the enrichment, either in the mantle or the crust, has long been debated. In this new approach, the combination of fluid-mobile trace elements (characteristic of subduction) and volatile concentrations from melt inclusions with whole rock isotope (Sr-Nd-Pb) and trace element analysis will allow us to distinguish potential crustal and mantle components, a significant obstacle to positively identifying mantle hydration. Analytical techniques for melt inclusions have greatly benefited from advancement in microbeam technology. Major elements and volatiles (S, Cl, and F) will be analyzed by electron microprobe at Oregon State University while trace element abundances will be measured by ion microprobe at Arizona State University. Whole isotope analyses will be conducted using the new TIMS facility at University of Texas at Austin resulting in collaborative research at several institutions. Broader impacts of this research include training of undergraduate students in petrologic techniques and the continued development of early career scientists.

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (06) Enabling Technologies and specific Challenge Topic 06- DA-102 Tool Development for the Neurosciences. Nervous systems create behaviors as a result of the concerted activity of networks of interconnected neurons, analogous to the way that companies often design new products as the result of concerted activity of multiple small groups of workers. Understanding how these networks function of course requires knowing how the neurons that make them up are interconnected and what the activity of the network's neurons is, just as understanding how a group of humans functions requires knowing who talks to whom and what is being said. However, individual neurons also have intrinsic active properties that make them respond to identical input in neuron-specific ways. These differences in intrinsic active properties are analogous to differences in human personality and have analogous results: a person's response to a given input, e.g., a statement, will differ depending on the person's overall personality and the mood she or he is in at the moment. It is thus impossible to understand how neural networks function without knowing the intrinsic active properties of the network's neurons. These properties result from the concerted activity of electrical currents in the individual neurons;neurons with different intrinsic active properties having different complements of electrical currents. One way to define neuron intrinsic active properties would thus be to describe all these membrane currents, which would allow computer modeling to predict neuron intrinsic active properties and neuron response to input on the basis of those properties. Unfortunately, present experimental techniques do not allow measuring all a neuron's membrane conductances in an individual-neuron-by-individual neuron manner. This application proposes an alternative approach for characterizing neuron intrinsic active properties, and identifying a neuron's complete set membrane currents, individual-neuron-by-individual neuron. The key idea is that measuring the response of individual neurons to experimental perturbation (in the proposed research, to the injection of electrical current) allows neuron intrinsic properties to be described in great detail. What specific input is used does not matter provided the input is complicated enough that it mimics the full range of input that a neuron will ever receive, and thus elicits the full range of responses that a neuron will ever produce. It is therefore proposed to use random perturbation sequences, as random input contains the most information per time of any sequence. Another hypothesis is that, if the perturbation is complicated enough, only one set of neuron membrane currents would be able to reproduce the observed neuron responses. This technique would thus allow building models of neurons on the membrane current level on an individual-neuron- by-individual neuron basis from every neuron recorded from. These ideas have been tested on a preliminary level using computer models of neurons and experiments in a particularly experimentally-advantageous and well-investigated system, the pyloric neural network of the lobster. However, this early work has not addressed an issue of particular importance to this submission: whether complicated perturbation can distinguish between neurons in control saline and under the influence of substances such as modulatory neurotransmitters (and drugs of abuse;see Relevance, below) that change a neuron's membrane current make-up and thus its intrinsic active properties. They have also not been tested in less well-understood systems or in vertebrate nervous systems. This application proposes to address these lacks by further work in the pyloric network, in sensory and behavior-generating neurons in the crab, and in two types of sensory neurons in a vertebrate. Demonstration that these techniques can distinguish between neurons on the basis of their intrinsic active properties, distinguish between unmodulated (control) neurons and modulated neurons, and build accurate, current-based neuron models in both control and modulated states, in all these systems (in all cases key model predictions will be tested experimentally) would be strong evidence that these ideas and techniques are generally applicable across nervous systems. PUBLIC HEALTH RELEVANCE: Neuron intrinsic active properties are undoubtedly important in many aspects of nervous system plasticity, including learning and memory. Most important in the present context is that psychoactive drugs likely exert some of their effects by changing neuron intrinsic active properties. The proposed physiological and modeling techniques, if validated as suggested here, would provide a new method for measuring the effects of psychoactive drugs and the normal function of the neural networks these drugs affect. The data could suggest novel treatment approaches for drug addiction and drug-induced nervous system damage.

DESCRIPTION (provided by applicant): The 2003 New Freedom Commission on Mental Health report stated that mental health care must be transformed to promote recovery, both in the sense of the outcome of reduced or eradicated signs and symptoms of mental illness and in the sense of the process of living a full life in the community life even if individuals continue to experience signs and symptoms of serious mental illness. Some research involving persons with enduring mental illnesses, however, suggests that many people with serious mental illnesses, while residing in their communities, have not achieved a sense of belonging or acceptance as members of it. In our research, we have described such limited community participation as "program citizenship," involving high dependence on mental health staff and systems for social contact and support. Full citizenship, we have argued, involves a strong connection to the rights, responsibilities, roles, and resources that society makes available to its members, and to supportive interpersonal relationships in one's community. Yet does supporting the rights, responsibilities, valued roles, material resources, and social relationships of people with serious mental illnesses involve anything different than what is involved in supporting those same five R's among adults in general, or among adults who have experienced other significant life disruptions? Using a combination of qualitative and quantitative research methods, we propose to address this question through two specific research aims. First, we will study the perspectives and processes involved in claiming, or reclaiming, one's citizenship for persons whose life trajectories have been disrupted by a serious mental illness, a serious physical illness, military service, or incarceration, and for those who have not experienced these disruptions. Second, we will develop and pilot a measure assessing those elements of citizenship identified as being especially relevant to persons with mental illness. Following successful completion of this research we plan to validate our citizenship measure, determine its convergent and divergent validity in relation to measures of related constructs, and design, implement, and evaluate an experimental intervention to support and enhance the citizenship of people with serious mental illnesses. PUBLIC HEALTH RELEVANCE: Development of a measure of citizenship may lead to development of interventions aimed at facilitating the achievement of citizenship and increased community inclusion of people with serious mental illnesses. Thus the proposed exploratory study is a relevant public mental health goal, one that is related to the New Freedom Commission's vision of a full life in the community for people with psychiatric disabilities. This goal, in fact, has been, along with development of effective community-based treatments, integral to the National Institute of Mental Health's key role in the community mental health movement that began more than forty years ago.

The release and movement of magmatic volatile components, including water, carbon dioxide, sulfur, and chlorine, exert significant control on the conditions of volcanic eruptions and on the transport and deposition of potential ore metals. Many of the parameters critical for understanding these processes are invisible to direct observations because they occur up to several kilometers beneath the surface of the Earth. Researchers have suggested that other trace elements both in the magma and in crystals forming within it may be used as a proxy for interpreting volatile behavior in magma and fluids. However many of the basic variables which describe how these elements are incorporated into crystals are unknown or are in question.

This study builds off observations about enrichment in different trace elements analyzed in crystals from the recent eruption (2004) of Mount St. Helens by 1) conducting hydrothermal experiments at various conditions to try to better constrain many of these questionable variables and 2) expand on the work at Mount St. Helens to look for similar elemental variations at other volcanoes, including Mt. Pinatubo, Philippines; Augustine volcano, Alaska; and Mt. Guardia, Lipari. Specifically, this work will focus on an experimental and analytical study of the elements, Li, Cu, Zn, Pb, W, and Mo. These elements are of particular interest as prior studies have suggested they are likely to be transported by volatiles (such as water, CO2, etc). The experimental results will be integrated with observations from multiple volcanic centers to fully understand the origins of these element enrichments and how this relates to the movement of volatiles in silicic magma systems and how volatile transfer influences processes of eruption and mineral deposit formation.

Historical experience tells us that volcanic eruptions can directly cause short-term (few years) global climate perturbations through the release of gases to the atmosphere. What is less clear is the capacity for very large eruptions to produce catastrophic and/or long-lasting climate change. Such eruptions lie outside recorded human experience but their products are evident in the geologic record. Among this class of events are the gigantic piles of frozen lava flows that make up continental flood basalt regions. Individual flood lava eruptions may be hundreds of times bigger than the largest historically-erupted lavas, with, potentially, proportionately severe effects on climate. The youngest and best-studied continental flood basalt province is the Columbia River Basalts (CRB), which formed around 16 million years ago and now cover about 200,000 square kilometers of the Pacific Northwest region of the United States. Previous studies of gas release associated with the eruption of these lavas have focused on late flows that post-date the main outpouring of basalt. This project employs a new approach that targets glassy volcanic ash found in the areas around the volcanic vents, rather than the equivalent crystallized, 'stony' lavas themselves. The glasses, and the crystals that they hold, preserve a higher fidelity record of eruption outgassing than do the lavas, allowing estimates of atmospheric pollution caused by the most intense phase of CRB activity. These estimates will constitute 'ground truth' that can help constrain, for instance, models for regional and global climate disturbance at the time of eruption.

Before now, studies of degassing from CRB have focused on the porphyritic Wanapum lavas (6% of the whole CRB), which post-date the peak activity of flood volcanism represented by the Grande Ronde lavas (70% of the whole CRB). The principle barrier to study of the Grande Ronde has been a perception that they are aphyric, i.e. they do not contain melt inclusion-bearing 'phenocrysts' (crystals that grew in the magma prior to eruption). Melt inclusions in crystals preserve the original gas content of the magma (chiefly H2O, CO2, S species) that can then be compared with fully degassed groundmass basalt to gain an estimate of gas loss. However, study of naturally water-quenched basaltic glasses from the vent areas of Grande Ronde lava flows shows that they do indeed contain melt inclusion-bearing phenocrysts, small, but nonetheless amenable to analysis by microbeam methods. Additionally, some of the glassy ash fragments have been quenched prior to degassing and can also be analyzed to gain an estimate of gas loss. The data will be used to estimate fluxes of S, H2O and CO2 to the atmosphere from CRB activity. This in turn will provide constraints on the potential of the CRB for cooling (due to S pollution of the atmosphere) vs. warming (due to CO2 release to the atmosphere) the Miocene climate, both of which hypotheses have been advanced by previous workers, but in both cases supported by little data. A further area of study is afforded by the fact that the glasses preserve a broader range of overall chemical compositions than do the equivalent lavas, potentially providing new insights into the ultimate origins of the flood basalt magmas.

? DESCRIPTION (provided by applicant): People with mental illness very often live in poverty as they can find it difficult to earn money from employment and often have to rely on social security benefits, which provide only a very low level of income. Living on a very low income means that they struggle to meet their basic needs, to pursue a fulfilling social life, and to maintain good physical health. Anxiety about money can exacerbate existing mental health problems. This project seeks to develop and test an intervention based in a community mental health center to help clients who are living on very low incomes to manage their money as well as possible, so that they are better able to cover their monthly expenses, feel less stressed about their finances, and can think about planning for a more stable financial future. Currently people with mental illness who have money problems receive very little support. Like many people living on low-incomes, many people with mental illness do not have access to the services essential for managing money, such as bank accounts, ATM cards, direct debit, ways to save, and short and long term loans. People who do not have access to these services can find it very difficult to manage money well, and may be taken advantage of by costly non-bank providers such as check cashers, pawnshops or payday lenders. Some people with mental illness who receive social security benefits but are deemed by a doctor to be incapable of managing their money, are assigned a `representative payee'. The payee receives their income, pays their major bills, and disburses the remainder to their clients. While this is helpful for som, the service is not available to everyone, and most people with mental illness prefer to retain control of their own income, if possible. This project will develop supports for people with mental illness that enable them to retain control of their own incomes, working within a citizenship-oriented approach to mental health care, which promotes recovery through linking people with mental illness to the rights, responsibilities, roles, resources and relationships necessary to achieve full membership in society. The specific aims of the project are to: train clinicians and peer staff so that they are able to integrate discussion of financial issues and concerns into thei work with clients; provide on-site services including financial counseling, peer support groups, help with opening a bank account, and a savings club, and; develop a `financial health' model which can be replicated by other providers of mental health services. We hypothesize that the supports we provide will result in clients becoming more financially healthy, and experiencing less stress related to their money problems.