Primary cilia: a novel signaling gateway to neural circuit modulation
Active Project Grant Awarded Last action
- Award ID
- RF1MH132710
- Recipient
-
University Of North Carolina At Chapel Hill UEI D3LHU66KBLD5
- Awarding agency
-
National Institute of Mental Health
National Institutes of Health, Department of Health and Human Services
- Obligated
- $2,189,936
Award facts
- Assistance listing
- 93.310 Trans-NIH Research Support
- Completion date 88% complete
- Funding agency
- Office of the Director National Institutes of Health, Department of Health and Human Services
- Place of performance
- Chapel Hill, NC 27599, USA
Award details come from USAspending.gov.
Description
- Abstract
- Primary cilium, a microtubule based antennae-like organelle, is present in every cortical neuron, and when defective, leads to ciliopathies. A distinguishing feature of ciliopathies is defective neural circuit formation and function. Disrupted construction and function of neural circuits in ciliopathies lead to disorders such as autism, intellectual disabilities, mood disorders, obesity, and epilepsy, thus implying a role for primary cilia in neuronal function and circuit dynamics. Primary cilia signaling may serve as a nonsynaptic signaling mechanism through which environmental signals can shape and refine neuronal circuits in health and disease. Nonetheless, how primary cilia signaling sculpts neuronal circuit dynamics and whether primary cilia can be CO-opted as a therapeutic conduit to mend neural circuit malfunctions remain enigmatic. We aim to resolve this challenge by defining the signaling mechanisms that are utilized by primary cilia to enable appropriate neuronal functions necessary for the emergence and maintenance of functional neural circuits in the brain. We will make this goal attainable by leveraging the latest advances in optogenetic and chemogenetic interrogation of signaling emanating from primary cilia, mapping neuronal ciliary receptome, profiling ciliary connectome within human cerebral cortical circuitry, live imaging cilia driven neuronal activity and transcriptional changes during neural circuit plasticity in living animals, and modeling human ciliopathies in brain organoids with the aim of rescuing circuit malfunctions using primary cilia as a tool. Collectively, this work will reveal how primary cilia activity is transformed into changes in neuronal circuit function and the pathways that must be successfully engaged to harness this insight in the service of ameliorating neural circuit disorders. These outcomes will offer a transformative opportunity to define new cellular principles of neural circuit formation and function and will open up new therapeutic avenues of neural circuit correction.
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| President And Fellows Of Harvard College | $393,824 | |
| Max Planck Florida Corp | $810,600 |
Quick answers
Who received award RF1MH132710?
RF1MH132710 was awarded to University Of North Carolina At Chapel Hill by National Institute of Mental Health (National Institutes of Health) on August 19, 2022.
How much is award RF1MH132710 worth?
$2,189,936 has been obligated on RF1MH132710.
Which agency awarded RF1MH132710?
National Institute of Mental Health (National Institutes of Health) awarded RF1MH132710, with funding from Office of the Director (National Institutes of Health).
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