Optogenetics for Parkinson's Research - Dr Conor Underwood

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Dr. Conor Underwood shares his expertise in neuromodulation, and why the Optogenetics Biopotential Telemeter was the right choice for his research on Parkinson’s Disease. This video is part one of our three-part interview with Dr. Underwood about his experiences.

Research Overview

Dr. Conor Underwood works in neuromodulation. This field of neuroscience aims to develop new therapies for neurological conditions using technologies that alter nerve activity and improve symptoms. Currently, his work investigates the abnormal activity of the thalamus in Parkinsonian rats.

Underwood’s focus is “looking at neuron network function in Parkinson's disease, seeing how it's dysfunctional and seeing how we can stimulate different areas in the brain - or different neurons in the brain - to restore neuronal network function and improve symptoms.”

His current research questions revolve around whether stimulation of the thalamus restores lost motor control in model animals of Parkinson’s.

“...we're stimulating neurons in the thalamus that might be important for both sleep and movement. So we hope that by stimulating neurons in the thalamus, we can improve both movement function and sleep disturbances.”

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Optogenetic vs. Electrical Stimulation

Although deep brain stimulation via electrical current has been a successful therapy for Parkinson’s Disease since the early 2000s, in Dr. Underwood’s opinion,   electrical stimulation is really quite crude.” Specifically, this is due to the non-selective stimulation of brain areas. Electrical stimulation affects both excitatory and inhibitory neurons, and the axons of neurons passing through this stimulation field from other areas of the brain. The side effects experienced with electrical stimulation can be attributed to this non-selective stimulation of different cell types.

We are using optogenetics because, firstly, this is the way the field is going.”

Instead, Underwood uses optogenetic stimulation. Optogenetics is cell-type specific, taking advantage of light-gated ion channels expressed in the brain through a viral vector, and under the control of a cell-specific promoter. For Dr. Underwood’s research, it was important to stimulate excitatory glutamatergic cells in the thalamus specifically. In this area of the brain “excitatory cells are thought to have an active role in facilitating movement, whereas the inhibitory cells in this region are thought to suppress movement.”

“In the past, we’ve used a CaM kinase II promoter, which at least in the thalamus is expressed exclusively in glutamatergic cells.”

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Tethered Telemeter Dilemna 

Prior to Dr. Underwood’s research, his lab had established preliminary data to support the stimulation of the thalamus as a therapeutic mechanism for Parkinson’s Disease.

“Going into this study, the lab had published a paper where they'd stimulated thalamus cells in Parkinsonian rats for a few minutes and found improvements in forelimb function. That's great, but ultimately they've only stimulated for two minutes - and for a therapy to be effective, it needs to be effective for months to years in patients.

To get the data they needed, Dr. Underwood’s lab needed a solution that could provide chronic stimulation for months at a time, without restricting animal movement or behavior. Many of the behavioral tests in this study required a large amount of animal handling, which would not be achievable with a tethered stimulation system.

Dr. Underwood knew that a tethered system would be impractical for chronic recording. “...you really can't do [this experiment] with a conventional tethered system, where you connect an animal to a Benchtop LED with a tether, simply because the animal will remove that tether.”

“My understanding is there are a few other technologies on the market that can provide wireless optogenetic stimulation, but they do so via a battery that's implanted on the head and it's not rechargeable. So for us, that really wasn't an option because we really wanted to stimulate for weeks to months.

Early Adopter of the Kaha Optogenetics Telemeter

We really had a need for an implantable system that could give us continuous stimulation reliably.

Dr. Underwood’s lab was one of the first research groups to test our Kaha Sciences Optogenetics Biopotential Telemeter. For Dr. Underwood, the Optogenetics Telemeter filled a gap in the market, providing the wireless, continuous stimulation and data collection he needed for a pre-clinical study. The capacity to provide stimulation with a rechargeable telemeter isabsolutely essential for researchers doing pre-clinical work,” particularly “with the view of taking that to larger animals and patients subsequently.”

“Our experience with the Kaha telemeters is they provide really reliable stimulation. Once stimulation is up and running and you've recovered the animal from surgery... Once you turn the stimulator on, it will stay on as long as you want and will provide continuous stimulation until you turn it off.

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Dr. Conor Underwood is a Postdoctoral Research Fellow at the University of Otago (UoO) in Dunedin. As a passionate early-career researcher, Conor investigates the brain circuitry which controls voluntary and involuntary muscle movements. His recent studies investigate akinesia in Parkinson's Disease, and whether optogenetic stimulation of the thalamus can restore motor function.

Hear more about how Dr. Conor Underwood's research uses the Optogenetics Telemeter: