Krishna Jayant, Michael Wenzel, Yuki Bando, Jorndan P Hamm, Nicola Mandriota, Jake H Rabinowitz, Ilan Jen-La Plante, Jonathan S Owen, Ozgur Sahin, Kenneth L Shepard, and Rafael Yuste. Flexible Nanopipettes for Minimally Invasive Intracellular Electrophysiology In Vivo. Cell Reports January 2, 2019, DOI:

Intracellular recordingsin vivoremains the best tech-nique to link single-neuron electrical properties tonetwork function. Yet existing methods are limitedin accuracy, throughput, and duration, primarily viawashout, membrane damage, and movement-induced failure. Here, we introduce flexible quartznanopipettes (inner diameters of 10–25 nm andspring constant of ~0.08 N/m) as nanoscale analogsof traditional glass microelectrodes. Nanopipettesenable stable intracellular recordings (seal resis-tances of 500 to ~800 MΩ,5 to ~10 cells/nanopip-ette, and duration of ~1 hr) in anaesthetized andawake head-restrained mice, exhibit minimal diffu-sional flux, and facilitate precise recording and stim-ulation. When combined with quantum-dot labelsand microprisms, nanopipettes enable two-photontargeted electrophysiology from both somata anddendrites, and even paired recordings from neigh-boring neurons, while permitting simultaneous popu-lation imaging across cortical layers. We demon-strate the versatility of this method by recordingfrom parvalbumin-positive (Pv) interneurons whileimaging seizure propagation, and we find that Pv de-polarization block coincides with epileptic spread.Flexible nanopipettes present a simple method toprocure stable intracellular recordingsin vivo.