TY - JOUR
T1 - In situ electrochemical generation of nitric oxide for neuronal modulation
AU - Park, Jimin
AU - Jin, Kyoungsuk
AU - Sahasrabudhe, Atharva
AU - Chiang, Po Han
AU - Maalouf, Joseph H.
AU - Koehler, Florian
AU - Rosenfeld, Dekel
AU - Rao, Siyuan
AU - Tanaka, Tomo
AU - Khudiyev, Tural
AU - Schiffer, Zachary J.
AU - Fink, Yoel
AU - Yizhar, Ofer
AU - Manthiram, Karthish
AU - Anikeeva, Polina
N1 - Funding Information:
We thank D. Kim and F. Zhang for the generous gifts of the plasmids and cell lines. This work was funded in part by the National Institute of Neurological Disorders and Stroke (5R01NS086804) and the National Institutes of Health (NIH) BRAIN Initiative (1R01MH111872). This work made use of the MIT MRSEC Shared Experimental Facilities under award number DMR-14-19807 from the National Science Foundation (NSF). Funding for this research was also provided by the Department of Chemical Engineering at MIT. J.P. is a recipient of a scholarship from the Kwanjeong Educational Foundation. J.H.M. and Z.J.S. are supported by NSF Graduate Research Fellowships under grant number 1122374. T.T. was supported by the NEC Corporation. S.R. acknowledges funding support from the NIH Pathway to Independence Award (National Institute of Mental Health 1K99MH120279-01) and a grant from the Simons Foundation to the Simons Center for the Social Brain at MIT.
Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - Understanding the function of nitric oxide, a lipophilic messenger in physiological processes across nervous, cardiovascular and immune systems, is currently impeded by the dearth of tools to deliver this gaseous molecule in situ to specific cells. To address this need, we have developed iron sulfide nanoclusters that catalyse nitric oxide generation from benign sodium nitrite in the presence of modest electric fields. Locally generated nitric oxide activates the nitric oxide-sensitive cation channel, transient receptor potential vanilloid family member 1 (TRPV1), and the latency of TRPV1-mediated Ca2+ responses can be controlled by varying the applied voltage. Integrating these electrocatalytic nanoclusters with multimaterial fibres allows nitric oxide-mediated neuronal interrogation in vivo. The in situ generation of nitric oxide in the ventral tegmental area with the electrocatalytic fibres evoked neuronal excitation in the targeted brain region and its excitatory projections. This nitric oxide generation platform may advance mechanistic studies of the role of nitric oxide in the nervous system and other organs.
AB - Understanding the function of nitric oxide, a lipophilic messenger in physiological processes across nervous, cardiovascular and immune systems, is currently impeded by the dearth of tools to deliver this gaseous molecule in situ to specific cells. To address this need, we have developed iron sulfide nanoclusters that catalyse nitric oxide generation from benign sodium nitrite in the presence of modest electric fields. Locally generated nitric oxide activates the nitric oxide-sensitive cation channel, transient receptor potential vanilloid family member 1 (TRPV1), and the latency of TRPV1-mediated Ca2+ responses can be controlled by varying the applied voltage. Integrating these electrocatalytic nanoclusters with multimaterial fibres allows nitric oxide-mediated neuronal interrogation in vivo. The in situ generation of nitric oxide in the ventral tegmental area with the electrocatalytic fibres evoked neuronal excitation in the targeted brain region and its excitatory projections. This nitric oxide generation platform may advance mechanistic studies of the role of nitric oxide in the nervous system and other organs.
UR - http://www.scopus.com/inward/record.url?scp=85087014866&partnerID=8YFLogxK
U2 - 10.1038/s41565-020-0701-x
DO - 10.1038/s41565-020-0701-x
M3 - Article
C2 - 32601446
AN - SCOPUS:85087014866
SN - 1748-3387
VL - 15
SP - 690
EP - 697
JO - Nature Nanotechnology
JF - Nature Nanotechnology
IS - 8
ER -