Abstract
In vivo pharmacology and optogenetics hold tremendous promise for dissection of neural circuits, cellular signaling, and manipulating neurophysiological systems in awake, behaving animals. Existing neural interface technologies, such as metal cannulas connected to external drug supplies for pharmacological infusions and tethered fiber optics for optogenetics, are not ideal for minimally invasive, untethered studies on freely behaving animals. Here, we introduce wireless optofluidic neural probes that combine ultrathin, soft microfluidic drug delivery with cellular-scale inorganic light-emitting diode (μ-ILED) arrays. These probes are orders of magnitude smaller than cannulas and allow wireless, programmed spatiotemporal control of fluid delivery and photostimulation. We demonstrate these devices in freely moving animals to modify gene expression, deliver peptide ligands, and provide concurrent photostimulation with antagonist drug delivery to manipulate mesoaccumbens reward-related behavior. The minimally invasive operation of these probes forecasts utility in other organ systems and species, with potential for broad application in biomedical science, engineering, and medicine.
Original language | English (US) |
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Pages (from-to) | 662-674 |
Number of pages | 13 |
Journal | Cell |
Volume | 162 |
Issue number | 3 |
DOIs | |
State | Published - Aug 1 2015 |
Funding
This material is based on work supported by the EUREKA NIDA R01DA037152 (M.R.B.), NIMH F31 MH101956 (J.G.M.), and NIDA K99DA038725 (to R.A.). We thank the Bruchas laboratory and the laboratory of Dr. Robert W. Gereau IV, in particular Tayler Sheahan and Dr. Judith Golden (Washington University) for helpful discussion. We thank Dr. Karl Deisseroth (Stanford University) for the channelrhodopsin-2 (H134), Dr. Garret Stuber (UNC) for the TH-IRES-Cre mice, the WUSTL Hope Center Viral Vector Core for viral packaging, and the WUSTL Pain Center for use of the rotarod and running wheels. All biomedical aspects of the device work were supported by a National Security Science and Engineering Faculty Fellowship of Energy (J.A.R.). The LED development was enabled by funding from the US Department of Energy, Division of Materials Sciences under award number DE-FG02-07ER46471 (J.A.R.), the NIH Common Fund NINDS R01NS081707 (J.A.R. and M.R.B.), and through the Materials Research Laboratory and Center for Microanalysis of Materials ( DE-FG02-07ER46453 ) (J.A.R.).
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology