Melanie A. Gainey - US grants
Affiliations: | University of California, Berkeley, Berkeley, CA, United States |
Area:
synaptic plasticityWe are testing a new system for linking grants to scientists.
The funding information displayed below comes from the NIH Research Portfolio Online Reporting Tools and the NSF Award Database.The grant data on this page is limited to grants awarded in the United States and is thus partial. It can nonetheless be used to understand how funding patterns influence mentorship networks and vice-versa, which has deep implications on how research is done.
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High-probability grants
According to our matching algorithm, Melanie A. Gainey is the likely recipient of the following grants.| Years | Recipients | Code | Title / Keywords | Matching score |
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| 2009 — 2010 | Gainey, Melanie Ann | F31Activity Code Description: To provide predoctoral individuals with supervised research training in specified health and health-related areas leading toward the research degree (e.g., Ph.D.). |
The Role of Glur2-Dependent Synaptic Scaling in Development and Plasticity @ Brandeis University DESCRIPTION (provided by applicant): Synaptic scaling is thought to be important in maintaining the stability of networks during development and activity-dependent plasticity. Under certain pathological conditions, such as epilepsy, the balance of excitation and inhibition is greatly perturbed, suggesting a lack of homeostatic scaling. Therefore, understanding synaptic scaling is crucial for understanding how neurons transfer information and remain plastic under normal and neuropathological conditions. Synaptic scaling has been observed in rat visual cortex as a result of development and monocular deprivation, suggesting that scaling is important in the activity-dependent refinement of circuits. However, studies have been limited by the inability to selectively block scaling and leave other forms of plasticity intact, and so the precise role of scaling in activity-dependent development and plasticity remains unclear. Scaling can be blocked in single cultured cortical neurons with an RNAi hairpin that targets the AMPA receptor subunit, GluR2, suggesting that GluR2 is critical for expression of scaling. This proposal will determine if GluR2 is also essential for scaling down in response to chronic heightened activity and which domain of the GluR2 subunit is required for its regulatory role in scaling. This proposal will also address whether scaling can be blocked in vivo with a conditional GluR2 knockout mouse model. Being able to block scaling in vivo is critical for elucidating the role of scaling in activity-dependent development. These questions will be persued using whole-cell voltage-clamp recordings of miniature excitatory postsynaptic currents (mEPSCs) in cultured cortical cells and acute slices containing layer 2/3 primary visual cortex. Together, the experiments proposed here will (1) further characterize the molecular regulation of synaptic scaling in cultured cortical cells, (2) develop a paradigm for selectively blocking scaling with high spatial and temporal resolution in vivo, and with this paradigm, (3) describe the role of synaptic scaling in experience-dependent development and plasticity in intact visual cortex. PUBLIC HEALTH RELEVANCE: Synaptic scaling is thought to be important in maintaining the stability of neural networks. Many neurological disorders, such as epilepsy, Rett Syndrome, and autism, are characterized by a perturbation in the balance of excitation and inhibtion, perhaps suggesting a deficit in homeostasic scaling. These studies will examine the mechanism and role of synaptic scaling in the intact nervous system, which may provide insight into the pathological processes that result in these disorders. |
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| 2014 — 2016 | Gainey, Melanie Ann | 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. |
@ University of California Berkeley DESCRIPTION (provided by applicant): How does sensory experience regulate circuit function in the cerebral cortex? This question has been intensively studied in rodent somatosensory (S1) cortex, where whisker experience or deprivation drive plasticity in the whisker receptive field map in layer (L) 2/3, whose basis has been studied at circuit and synaptic levels. Most prior work has focused on excitatory circuits, which undergo classical Hebbian plasticity in response to whisker deprivation. However, recent work shows that experience also drives a rapid reduction in inhibition (disinhibition) in L2/3 following whisker deprivation, which is a major novel step in whisker map plasticity. We do not yet understand the circuit basis for rapid disinhibition, including which projections and synapses are involved, and how disinhibition functionally affects sensory responses in vivo. Here I propose to determine the synaptic and circuit basis of rapid disinhibition within S1. I will use whole-cell neurophysiology and optogenetic techniques to identify whether rapid disinhibition occurs primarily in feed-forward inputs to L2/3, or in L2/3 recurrent circuits, and then to identify the specific synapses whose function is altered by deprivation. These recordings will be performed in transgenic mice with parvalbumin (PV)-positive interneurons fluorescently labeled for efficient targeted recordings. Next, I will determine whether rapid disinhibition produces detectable changes in firing rates or receptive fields of S1 neurons in vivo, using silicon tetrode recordings in anesthetized mice. Finally, I will determine whether feed-forward and recurrent L2/3 circuits in the Fragile X syndrome model mouse, Fmr1 -/-, undergo rapid disinhibition in response to whisker deprivation. These experiments will provide (1) a circuit-level description of which inhibitory circuits in L2/3, (2) and which specific synapses, mediate rapid disinhibiton following whisker deprivation and (3) a description of the spiking correlates of circuit-level disinhibition n the wildtype mouse, and (4) a circuit-level description of rapid disinhibition in the Fmr1 -/- mouse. The results will further our understanding of how the brain responds to changes in sensory input that occur in normal brains during development, injury, and learning and will provide insight on dysregulation in the neurological disorder, Fragile X syndrome. The results will also be relevant to several other neurodevelopmental disorders in which E-I ratio is abnormal, such as epilepsy, autism spectrum disorders, and chronic pain. This proposal will give me valuable optogenetic and electrophysiological training that will build on my previous molecular expertise on plasticity to position me for an independent research career. |
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