Unmasking neuromodulatory control of locomotion
Active Cooperative Agreement Awarded Last action
- Award ID
- U01NS136458
- Recipient
-
The Washington University UEI L6NFUM28LQM5
- Awarding agency
-
National Institute of Neurological Disorders and Stroke
National Institutes of Health, Department of Health and Human Services
- Obligated
- $3,390,475
Award facts
- Assistance listing
- 93.853 Extramural Research Programs in the Neurosciences and Neurological Disorders
- Completion date 79% complete
- Place of performance
- St. Louis, MO 63110, USA
Award details come from USAspending.gov.
Description
- Abstract
- Neuromodulators including dopamine and serotonin have profound effects on spinal circuits for locomotion. A wealth of pharmacological manipulations has shown that drugs mimicking or blocking these neuromodulators can change the properties of rhythmic motor output in the isolated spinal cord. However, these studies often conflict and cannot capture the normal range of behaviors expressed in vivo. Furthermore, IT is entirely unknown whether neuromodulators are released onto different spinal targets across different behaviors. Finally, neuromodulatory neurons are highly branched, making IT difficult to disambiguate the spinal VS supraspinal consequences of their action. We will leverage new tools for imaging and manipulating neuromodulator signaling, combined with the transparency and accessibility of the young zebrafish, and a quantitative modeling approach, to understand the effects of dopamine and serotonin on genetically defined components of the spinal locomotor circuit in vivo. First, we will measure the activity of neuromodulatory axons during three distinct behaviors, testing whether dopamine and serotonin axons differentially participate in these behaviors. Next, we will quantify neuromodulator release during these behaviors directly, both in the whole spinal cord and in genetically defined populations of neurons with distinct contributions to locomotion. We will then test the significance of descending neuromodulatory influence on spinal circuits by targeted axotomy that will allow disambiguation of the spinal and supraspinal consequences of neuromodulator release. Finally, using newly developed chemogenetic approaches, we will selectively block neuromodulatory receptors in motor neurons and measure the consequences on the three distinct behaviors in freely moving animals. Throughout the project, we will use experimental data to develop both single-segment and multi-segment computational models of neuromodulatory action, and in turn use these models to make testable predictions about circuits and behavior. Together, these experiments will reveal for the first time when and where dopamine and serotonin are acting in the spinal locomotor circuit, and how their actions influence behavior in vivo.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $421,852 | |
| Amendment | $0 | |
| Amendment | $0 | |
| Amendment | $1,517,020 | |
| Original award | $1,451,603 |
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| University Of Utah | $451,340 | |
| University Of Oregon | $227,008 | |
| Duke University | $351,540 | |
| Duke University | $315,381 | |
| University Of Oregon | $296,528 | |
| University Of Utah | $535,826 | |
| The University Of Edinburgh | $280,410 | |
| University Of Oregon | $248,067 | |
| University Of Utah | $420,014 | |
| Duke University | $400,689 |
Quick answers
Who received award U01NS136458?
U01NS136458 was awarded to The Washington University by National Institute of Neurological Disorders and Stroke (National Institutes of Health) on August 16, 2024.
How much is award U01NS136458 worth?
$3,390,475 has been obligated on U01NS136458.
On GovTribe
See this award's full record
- Every transaction and subaward
- The recipient's other awards and teaming partners
- Similar grant awards
- Ask GovTribe AI about this award