A flexible nanoelectrode net to investigate sub-cellular integration at the cortical surface

Interdisciplinary Areas: Engineering and Healthcare/Medicine/Biology, Micro-, Nano-, and Quantum Engineering

Project Description

Neurons deep in the cerebral cortex extend their dendrites vertically into the most superficial layer where they integrate extensive input from diverse brain regions. These layer 5 apical dendrites exhibit a myriad of regenerative events [1-3] (E.g.: NMDA, Calcium, Sodium spikes), and are believed to be fundamental to the overall input-output-gain of the neuron [1]. However, the spatio-temporal dynamics of dendritic activity, and the overall relationship between dendritic and somatic gain in vivo remains unknown. The small size the dendrites (<1 µm in diameter) and their location (<100 µm from the surface) precludes conventional whole-cell electrophysiology – the current gold-standard; while alternative approaches, such as calcium imaging, lack temporal resolution. Here, we aim to map the electrical dynamics of these apical dendrites in the somatosensory cortex of awake, behaving mice using a flexible vertical nanoelectronic platform (20-40 um in height and 200-500 nm tip diameter). Our custom, fabricated array (64-128 vertical silicon nanoelectrodes) placed on the surface of the brain will penetrate <60 µm deep and form a tight electrical seal with dendritic branches. Readout will be accomplished through heavily multiplexed low noise CMOS amplifiers. This project will combine intracellular and nanoelectrode recordings [4], two-photon calcium imaging [5], optogenetic activation, spike sorting, and high-speed imaging to understand how dendritic integration shapes cortical output during active sensation [6].

Start Date

May 2019 

Postdoc Qualifications

The ideal candidate will have a PhD in electrical engineering, biomedical engineering, biophysics, neuroscience or other related fields. Other relevant background and interests include, but are not limited to, experience with mouse physiology, electrophysiology, two-photon imaging, microfabrication and integrated electronics. The successful candidate will work in a multi-disciplinary environment and have deep interest in dissecting the mechanisms of neural circuitry, be an excellent communicator, and work collaboratively.

Co-advisors

Prof. Krishna Jayant (BME)

Prof. Scott Pluta (Biology)

References

1. Murayama, M.; et al., Nature 2009, 457, (7233), 1137-1141.

2. Schiller, J.; et al., Nature 2000, 404, (6775), 285

3. Stuart, G. J.; Spruston, N. Nature neuroscience 2015, 18, (12), 1713-1721
 
4. Jayant, K.; et al, Cell Reports (in press) 
 
5. Jayant, K.; et al., Nature Nanotechnology 2017, 12, 335–342, 
 
6. Pluta S.R.; et al., Neuron 2017, 94, (6), 1220-1233