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High-probability grants
According to our matching algorithm, Christopher Ford is the likely recipient of the following grants.
Years |
Recipients |
Code |
Title / Keywords |
Matching score |
2020 — 2021 |
Ford, Christopher Peter |
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. |
Regulation of Striatal Acetylcholine Transmission by Choinergic Interneurons @ University of Colorado Denver
Project Summary The striatum is central to motivated behaviors and goal-directed actions. Neuromodulation by acetylcholine (ACh) plays a major role in regulating striatal circuits and resulting behaviors. ACh levels within the striatum are the highest in the CNS. Cholinergic transmission is involved in multiple basal ganglia based functions including the control of voluntary movement, motor and associative learning, as well as reward. Dysfunctions in acetylcholine (ACh) signaling in the striatum are associated with a variety of neurological movement disorders including Parkinson?s disease, Huntington?s disease, and dystonia. Identifying how these dysfunctions occur is limited by a lack of understanding of the basic mechanisms of cholinergic transmission. While both nicotinic and muscarinic receptors are expressed in the striatum, ACh does not directly evoke post-synaptic events at most synapses that can be detected with conventional electrophysiological approaches. Instead cholinergic receptors modulate striatal inputs or indirectly alter the excitability of post-synaptic neurons through multistep intracellular cascades. This proposal will examine the dynamics of ACh at muscarinic synapses using the viral expression of GIRK channels that was developed in the last funding period. The dynamics of ACh will be compared in control and disease states following loss of dopamine. The proposed studies are expected to be significant in that they have to potential to determine specific mechanisms that regulate cholinergic transmission and identify the dysregulations that occur in an animal model of Parkinson?s disease.
|
0.958 |
2021 |
Ford, Christopher Peter |
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. |
Encoding Dopamine Signals in the Mesolimbic System @ University of Colorado Denver
Project Summary Alterations in the dopamine system underlie a variety of psychiatric disorders including drug addiction. In order to understand how these alterations arise, it is necessary to first understand the basic mechanisms that regulate how dopamine mediates transmission. One of the key brain regions where many drugs of abuse, including cocaine, mediate their rewarding and reinforcing properties is within the nucleus accumbens and dorsal striatum. Despite a wealth of literature examining the interaction between cocaine and the dopamine system in striatal circuits and an understanding of the cellular and molecular singling pathways of dopamine receptors, relatively little is known in regards to how the synaptic release of dopamine leads to the activation of post-synaptic receptors, where those receptors are located and how cocaine alters transmission and the synaptic activation of dopamine receptors. To address this, the current proposal will use a novel approach to examine the location and synaptic activation of D2 receptors and GABAA receptors in medium spiny neurons of the dorsal striatum and nucleus accumbens. By simultaneously imaging D2-receptors while electrophysiologically measuring their synaptic activation by dopamine the application will determine how D2-receptors encode nigrostriatal and mesolimbic dopamine signals. Additionally, the proposal aims to examine if the synaptic corelease of GABA and dopamine are differentially regulated and how cocaine exposure alters receptor synaptic activation. These experiments will test the central hypothesis that striatal dopamine transmission occurs in a point-to-point synaptic manner. The significance of this work will be to determine how dopamine receptors across striatal regions encode dopamine release and how this is altered following exposure to drugs of abuse. The proposed studies are expected to be significant in that insights in to the specific mechanisms that regulate dopamine transmission, GABA co-transmission and how they are altered by exposure to cocaine are expected to directly lead to testable hypothesis regarding the dysregulations in this system that occur as a result of chronic drug abuse and addiction.
|
0.958 |