Nanoscale electrical and optical neurotechnologies for mapping the sub-cellular neural code

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Bio: Krishna Jayant received his B.Tech degree in electrical engineering from the National Institute of Technology (NIT) Trichy, India in 2005, where as part of his bachelor’s thesis he worked on bio-inspired optimization techniques. After brief research stints at IISc Bangalore (2005-2006), and the University of Bologna (2006-2007), both in the area of microelectronics, he joined Cornell University, Ithaca NY, where he received his M.S/PhD in electrical engineering in 2014 working with Prof. Edwin C. Kan on Bioelectronics. He then joined Columbia University for postdoctoral research training with Profs. Rafael Yuste, Ken Shepard, and Ozgur Sahin in the field of circuit neuroscience, biophysics, and CMOS integrated neurotechnology. Here, he was awarded the prestigious Kavli Post-Doctoral Fellowship for carrying out work at the intersection of nanoscience and neuroscience. As an Assistant Professor of Biomedical Engineering at Purdue, his laboratory focuses on elucidating the biophysical features involved in neural computation and their behavioral relevance using a combination of nano-electrophysiology, optical microscopy, CMOS integrated systems, and modeling. His research is supported by the NIH Trailblazer Award, the HFSP young investigator grant, and the Ralph E. Powe Junior Faculty Enhancement Award.

Abstract: Single neuron computations span multiple scales – from synapse to dendrite to the soma. Mapping single neuron input-output electrical transformations as well as decoding their computational rules remains a central question in neuroscience and a key need for a thorough understanding of both microcircuit function as well as behavioral output. In this talk I will present both published and ongoing work in which we exploit multimodal approaches to address key challenges in the field of single neuron computation. In the first part of my talk, I will describe our work on mapping dendritic spine electrical dynamics. Dendritic spines, characterized by a small head (volume~0.01-0.1μm3) and narrow neck (diameter~0.1μm, length~1μm), are the primary site of excitatory synaptic input in the mammalian brain. Synaptic inputs made onto spines first integrate onto dendrites, and subsequently propagate towards the soma and axon initial segment, where they further integrate with other inputs to determine overall action potential output. Elucidating the electrical properties of spines is thus paramount for understanding the first steps along this signal processing chain. I will describe our work using quantum-dot labeled quartz nanopipettes (15-30 nm diameters) under two-photon visualization for targeted intracellular recordings from spines1 and small pre-synaptic terminals. I will show through detailed experiments that (i) spines receive large EPSPs (25-30mV), and (ii) estimated neck resistances are large enough to influence electrical isolation (mean ~420 M?), and filter synaptic input as it invades the dendrite. I will then briefly describe the theoretical implications of these properties2 and describe key advances in amplifier design that can enable previously unattainable experiments on spines4. I will then describe recent results from my lab using two-photon holography to stimulate spines in 3D to unravel dendritic spine co-operativity across dendrites. In the second part of this talk, I will switch gears and describe a new method in which I combine the flexible property of these nanopipettes with microprisms to enable simultaneous two-photon calcium imaging and targeted intracellular electrophysiology from dendrites in vivo during behavior3. Last, I will give a succinct overview of our recent work at Purdue, including two-photon compatible transparent nanoelectrode arrays for mapping dendritic activity from the surface of the awake-behaving brain. I will conclude by presenting a snapshot of key collaborative projects at Purdue that highlight the integration of nanoscience and neuroscience.

1  Jayant, K. et al. Targeted intracellular voltage recordings from dendritic spines using quantum-dot-coated nanopipettes. Nature Nano, (2017).

2  Thibault Lagache, Krishna Jayant & Rafael Yuste,. Electrodiffusion modelling of spine voltage dynamics. J. Comp. Neurosci, 2019

3  Jayant, K. et al. Flexible nanopipettes for motion-insensitive intracellular electrophysiology in vivo. Cell Reports (2019).

4. Shekar, S., Jayant, K., et al,  A miniaturized multi-clamp CMOS amplifier for intracellular neural recording, Nature Electronics, 2019