We 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.
You can help! If you notice any innacuracies, please
sign in and mark grants as correct or incorrect matches.
Sign in to see low-probability grants and correct any errors in linkage between grants and researchers.
High-probability grants
According to our matching algorithm, Amanda M. Willard is the likely recipient of the following grants.
| Years |
Recipients |
Code |
Title / Keywords |
Matching
score |
| 2016 — 2018 |
Willard, Amanda M |
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.). |
Investigation of Progressive Behavioral Deficits and Circuit Dysfunction in the Striatum During Gradual Dopamine Depletion @ Carnegie-Mellon University
? DESCRIPTION (provided by applicant): Parkinson's disease (PD) is a debilitating movement disorder that results from the gradual loss of dopaminergic innervation of the striatum. Our goal is to study the synaptic function of circuits in the striatum under conditions of progressively decreasing levels of dopamine by utilizing a modified 6-hydroxydopamine animal model of PD. This modified model involves gradually depleting dopamine over 1-2 months, instead of the traditional 2-3 days. The focus of our investigation of synaptic function will be within the striatum, which acts as the main input nucleus of the basal ganglia. Activity within the striatum i modulated by dopamine, and thus, when dopamine is depleted; the striatum falls into a state of dysfunction. This causes an imbalance between the two output pathways of the striatum that have opposing effects on movement: output from the motor depressing `indirect' pathway is too strong, while output from the motor facilitating `direct' pathway is too weak. We know from previous studies of acutely dopamine depleted animals that optogenetically increasing direct pathway activity restores movement in a mouse model of PD, suggesting that circuit dysfunction in the striatum plays a causal role in the expression of motor deficits. However, we know very little about the progression of circuit dysfunction, or compensatory plasticity leading up to the appearance of motor impairments, an understanding that may be critical to halting disease progression before it becomes irreversible. Thus, the short-term objective of this proposal is to utilize a gradual depletion paradigm to study how neural circuits in the striatum, a primary state of brain dysfunction in PD, adapt to progressive dopamine loss. In Aim 1, we will determine how long-term depression at excitatory synapses changes as a function of progressive dopamine loss. These experiments will determine whether this loss of long-term depression correlates with the onset of motor symptoms. In Aim 2, we will evaluate the innervation of fast-spiking interneurons onto direct and indirect pathway medium spiny neurons as a function of progressive dopamine loss. Together we hope that these results will provide insights into the progression of synaptic dysfunction in the striatum during progressive dopamine and in turn, aid in correlating synaptic dysfunction to motor deficits in disease. The long-term goal is to be able to selectively target and intervene at a certain level of dopamine depletion to prevent further circuit dysfunction that would otherwise lead to more severe motor impairment in the progression of PD.
|
1 |