2006 — 2007 |
Pratt, Kara Geo |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
Developmental Regulation of Neural Circuit Properties
[unreadable] DESCRIPTION (provided by applicant): The input-output function of a neuron is defined by the combined expression of synaptic and intrinsic properties. These properties are not static and many forms of plasticity involve coordinated changes in both synaptic strength and intrinsic excitability. However, the way in which a neuron co-regulates these properties is not well-understood. This project aims to define the underlying relationship between a neuron's intrinsic and synaptic properties, focusing on the retino-tectal circuit of the tadpole, where postsynaptic tectal neurons receive direct input from retinal ganglion cells. A series of whole-cell electrophysiological recordings will be carried put in order to characterize the relationship between intrinsic and synaptic properties expressed in individual neurons. Aim 1 characterizes how synaptic and intrinsic properties of the tectal neurons change throughout development of the retino-tectal circuit. Aim 2 explores how specifically altering either an intrinsic or synaptic property during development may alter (1) the input-output function of the neuron, (2) circuit formation. Aim 3 addresses how modulation may regulate intrinsic and synaptic properties and, ultimately, circuit function. Dysregulation of these processes may ultimately lead to pathological states such as epilepsy. [unreadable] [unreadable]
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0.966 |
2017 — 2019 |
Pratt, Kara Geo |
P20Activity Code Description: To support planning for new programs, expansion or modification of existing resources, and feasibility studies to explore various approaches to the development of interdisciplinary programs that offer potential solutions to problems of special significance to the mission of the NIH. These exploratory studies may lead to specialized or comprehensive centers. |
Project 2: the Role of Presenilin in a Developing Visual Circuit
Abstract The way a neural circuit functions is largely determined by how it is built. This project aims to elucidate the role of presenilin (PS) in a developing visual system. Although discovered, and named, in the context of Alzheimer's disease, we now know this molecule carries out a multitude of functions that may be important during development. As the catalytic component of ?-secretase, PS has substrates that are involved in neurogenesis, neural differentiation, axon guidance, and synapse formation. This suggests that PS is an important and global molecule for proper neural circuit development. The role of this molecule in neural circuit development and function, however, has not been determined, and is the main objective of this proposal. To provide comprehensive and detailed information about the role of this molecule throughout all stages of nervous system development, we will use Xenopus tadpole visual system as our model. This classic model is especially well-suited to carry out a comprehensive study of PS because it is the only vertebrate model that allows for all stages of neural development to be studied, at the cell, circuit, and behavioral levels, in vivo. To test the role of PS in the development of the tadpole visual system, PS function will be inhibited pharmacologically or genetically, at different key stages of development, and a series of assays to test visual system function at the behavioral, circuit, and cellular level will be carried out. To assess visual system function at the behavioral level, visually guided avoidance behaviors will be assessed using a moving dot assay. To study the effect of altered PS function at the circuit level, light of different intensities is projected onto the retina and the resulting electrical responses of single tectal neurons (neurons that comprise the optic tectum, the visual center of the amphibian brain), recorded. To quantify effects at the cellular level, a series of electrophysiological recordings that are designed to measure many aspects of cellular electrophysiological properties, will be carried out. Several substrates of PS are known to be involved in axon guidance, and proper circuit function requires that axons make it to exact appropriate targets. Our model system is an excellent model to study long distance guidance of axons: retinal ganglion cells in the eye project their axons from the eye to the brain, cross the midline at the optic chiasm, and terminate in the contralateral tectum. To test the role of PS in the process, axons of the retinal ganglion cells in the eye will be imaged, in vivo, and control axons compared to axons in which PS function has been inhibited at various key stages of their journey. Deficits identified in visual system function will continue to be monitored later, in more mature tadpoles and froglets, to determine if deficits occurring during development manifest later in the more mature circuit. Combined, this work will provide a comprehensive and detailed characterization of the role of PS in the development and function of a neural circuit, from the cell to behavioral levels, and add insight about molecular mechanisms that coordinate and regulate proper neural circuit development.
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1 |
2022 — 2025 |
Pratt, Kara |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Development and Function of the Xenopus Tadpole Retinotegmental Projection
New-born neurons (brain cells) have the amazing ability to self-assemble into circuits – groups of functionally connected neurons. These circuits give rise to our perceptions, thoughts, emotions, and behaviors. Understanding how neurons self-assemble into circuits is an important aim in the field of neuroscience, and it is the overall aim of this project. This would be difficult to study in mammals with their billions of neurons, complex circuits, and variable behaviors. This project studies a more experimentally tractable circuit: the developing visual system of the African Clawed Frog (Xenopus) tadpole. Previous studies on the tadpole visual system have focused on the retinotectal projection, a circuit consisting of the synapse between the retinal ganglion cells (RGCs) in the eye and the optic tectum, a major visual processing center on the dorsal (top) surface of the amphibian midbrain. In preparatory work for the current project, we characterized a second projection between the retinal ganglion cells from the Xenopus eye and the ventral (bottom) midbrain called the retinotegmental projection. Preliminary data indicate that these two projections are built differently and carry out different functions within the visual system. The goal of this project is to provide a detailed description of the development and function of the retinotegmental projection. Overall, this work will contribute important new insights about how neural circuits form and carry out specific functions. Educational and broader impact activities for this project include teaching a “Vision and Art” course for non-science undergraduates, and an upper-level developmental science lab course in which students design and carry out experiments to determine how environmental factors impact the developing Xenopus embryo. <br/><br/>How neurons self-assemble into circuits that give rise to behaviors is a fundamental question in neuroscience. For decades, the Xenopus tadpole retinotectal projection – the synapse between the retinal ganglion cells (RGCs) in the eye and the midbrain optic tectum – has served as a popular model to study this question. But the retinotectal projection is only one of several components of the vertebrate visual system. Our recent work shows that color-dependent phototaxis in tadpoles does not require the optic tectum, but does require the tegmentum, a region of the midbrain that lies ventral to the optic tectum. We also found several color-tuned neuronal populations in the tegmentum. Through additional anatomical and electrophysiological studies, we identified a retinotegmental projection, a direct projection from the RGCs to the midbrain tegmental neurons. This projection appears to lack the developmental plasticity displayed by the retinotectal projection, suggesting a more hard-wired circuit. A highly conserved retinotegmental projection, termed the accessory optic system (AOS), has been described across a wide range of adult vertebrates, from frogs to humans. It is associated with optomotor and optokinetic responses – reflexive body and eye movements, respectively, that stabilize vision as the organism moves through space. It is likely that the retinotegmental projection we are studying in the tadpole is, at least in part, the AOS. Through a combination of electrophysiology-based approaches and circuit tracing, this work will provide a detailed description of the development and differentiation of the Xenopus tadpole retinotegmental projection and its role in processing visual stimuli.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
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0.915 |