VCU’s Aliza Ehrlich receives $3 million to study link between opioids and unexplored neuron structure

By Madeline Reinsel

A new five-year, $3 million grant from the National Institute on Drug Abuse will fund Aliza Ehrlich, Ph.D., as she investigates how opioid receptors on our brain’s neurons interact with a little-known neuronal structure called the primary cilium.

“We know it’s a really critical place for specialized signaling during development, but we have no idea what it does for opioid signaling and for pain relief,” said Ehrlich, an assistant professor in Virginia Commonwealth University’s School of Life Sciences and Sustainability in the College of Humanities and Sciences. Ehrlich will carry out the research alongside colleagues from the University of California, San Francisco and Stanford University.

Neurons, the nerve cells that transmit signals in our brains and throughout our bodies, have receptors on their surfaces called G-protein coupled receptors. When someone takes an opioid like morphine, specific receptors called mu-opioid receptors are activated. That causes neuronal signaling to quiet down, leading to pain relief. However, people can develop a tolerance and an addiction to opioids, which can also cause euphoria and respiratory depression at higher doses.

In her previous research, Ehrlich found that opioid receptors tend to accumulate in the primary cilium, an antenna-like protrusion on the surface of the neuron. But when she first made that discovery, Ehrlich had never even heard of the primary cilium.

“One day, I was looking under the microscope at a fluorescently tagged receptor. And I noticed that the receptor was in this little compartment sticking off of the cell body on the neuron,” said Ehrlich, who was then a postdoctoral researcher at McGill University in Montreal, Canada.

With this grant, Ehrlich plans to study when and why those receptors cluster in the primary cilium, and whether neurons will still react to opioids if their primary cilia are removed.

“What we'll be doing is essentially either blocking the opioid receptor from entering the primary cilium or removing the primary cilium from neurons that are activated by opioids, and comparing to normal unaltered neurons,” she said. “Then we’ll look at what happens to opioid signaling inside the neuron, and just as important, what happens to how the neuron actually behaves: does it still go quiet – become inhibited – when opioids are present, or does removing the cilium change that response?”

By understanding the role of the primary cilium when opioids are present, Ehrlich ultimately aims to learn how this largely overlooked structure shapes our body’s relationship with opioids – from how we respond to them to how we build tolerance or dependence.

“The grant is designed to study this aspect of opioid signaling and determine whether or not it contributes to a specific type of function like neuronal firing,” she said. “Which could go on to translate to how it changes our overall behavior.”