For the first time, cell cilia are found to be crucial to the 'motivation' of movement

The study was conducted on a mouse model of the disorder called Bardet-Biedl syndrome, and applied one of five proteins that regulate dopamine signaling, called dopamine receptors body 1

"Dopamine receptor 1 needs something to get in and out of neuronal cilia, which is necessary for proper signaling," said the study's lead author Kirk Mykytyn, associate professor of biochemistry and pharmacology at The Ohio State University School of Medicine

The research was published in the Journal of Neuroscience

Bardet-Biedl syndrome (BBS) is a human disorder known as ciliopathies, caused by ciliary dysfunction on a range of cell types, and is characterized by defects in multiple organ systems, adult blindness, obesity and intellectual disability

While the syndrome involves ciliary dysfunction throughout the body, Mykytyn's lab studied the neural components of BBS to determine the role of primary cilia in the brain

"These appendages are present in almost every cell type in the body and are ubiquitous in the brain," he said.

Mykytyn previously found that in a mouse model of Bardet-Biedl syndrome, loss of the BBS protein blocks the movement of specific types of receptors between primary cilia

In this work, the researchers engineered mice whose dopamine receptor 1-expressing neurons lack the BBS protein, or a mechanism required for cilia development

"This tendency to reduce activity and obesity is consistent with a reduction in dopamine receptor 1 signaling," Mykytyn said

"We know that animals with BBS become obese, which appears to be due to overeating

Study co-lead author Candice Askwith's electrophysiology lab, associate professor of neuroscience at Ohio State University, determined that the neurons retained their excitability -- further evidence that the reduced receptor signaling did not significantly damage neuronal circuits, resulting in behavioral outcomes in mice

"The idea that cilia are novel targets for modifying dopamine-dependent neuronal signaling and motivated behavior is very exciting,

In addition to providing a potential explanation for Bardet-Biedl syndrome in obesity, the findings suggest that primary cilia in the brain play a key role in the proper signaling of the dopaminergic system, which helps regulate motor control, motivation, and , reward and cognitive function

Toneisha Stubbs, Andrew Koemeter-Cox, James I.