Optogenetic Deconstruction of Deep Brain Stimulation

Abstract:

Deep brain stimulation (DBS) treats motor symptoms of Parkinson’s disease, but mechanisms remain poorly understood and DBS can modulate multiple neural elements. Optogenetics enables cell-type-specific activation, and we re-examined the role of STN neurons in mediating the symptom-relieving effects of DBS using Chronos-GFP expressed selectively in STN local cells in our unilateral 6-OHDA rat model of parkinsonism. Optogenetic stimulation of Chronos-expressing STN cells at 130 Hz reduced pathological circling behavior, in contrast to results with the slower ChR2 opsin. Further, optogenetic DBS of STN with Chronos exhibited a strong dependence on stimulation rates. In addition, optogenetic STN DBS at 130 Hz corrected the bias to use the unimpaired forepaw in forelimb stepping. These results indicate that direct optogenetic stimulation of STN neurons is effective in treating the symptoms of parkinsonism, provided that a sufficiently fast opsin is used. Further, these results highlight that the kinetic properties of opsins can have a strong influence on the effects of optogenetic activation / inhibition.

Seminar Details:

Date:  20 March 2025 (Thursday)

Time: 3:00pm – 4:00pm

Venue: Amphitheatre, Level 2, Duke-NUS

Host:

Asst Prof Alfred Sun

Principal Investigator

Neuroscience & Behavioural Disorders Programme

Duke-NUS

 

All are welcome. No registration is required. Light refreshment will be served after the seminar.