. Significance: Light-sheet fluorescence microscopy (LSFM) is a powerful technique for high-speed volumetric functional imaging. However, in typical light-sheet microscopes, the illumination and collection optics impose significant constraints upon the imaging of non-transparent brain tissues. We demonstrate that these constraints can be surmounted using a new class of implantable photonic neural probes. Aim: Mass manufacturable, silicon-based light-sheet photonic neural probes can generate planar patterned illumination at arbitrary depths in brain tissues without any additional micro-optic components. Approach: We develop implantable photonic neural probes that generate light sheets in tissue. The probes were fabricated in a photonics foundry on 200-mm-diameter silicon wafers. The light sheets were characterized in fluorescein and in free space. The probe-enabled imaging approach was tested in fixed, in vitro , and in vivo mouse brain tissues. Imaging tests were also performed using fluorescent beads suspended in agarose. Results: The probes had 5 to 10 addressable sheets and average sheet thicknesses for propagation distances up to in free space. Imaging areas were as large as in brain tissue. Image contrast was enhanced relative to epifluorescence microscopy. Conclusions: The neural probes can lead to new variants of LSFM for deep brain imaging and experiments in freely moving animals.

Implantable silicon neural probes with integrated nanophotonic waveguides can deliver patterned dynamic illumination into brain tissue at depth. Here, we introduce neural probes with integrated optical phased arrays and demonstrate optical beam steering in vitro. Beam formation in brain tissue was simulated and characterized. The probes were used for optogenetic stimulation and calcium imaging.

15Most existing multi-compartment, mammalian neuron models are built from rodent data. However, 16 our increasing knowledge of differences between human and rodent neurons suggests that, to 17 understand the cellular basis of human brain function, we should build models from human data. 18 Here, we present the first full spiking, multi-compartment model of a human layer 5 cortical 19 pyramidal neuron. Model development balanced prioritizing current clamp data from the neuron 20 providing the model's morphology, while also ensuring the model's generalizability via preservation 21 of spiking properties observed in a secondary population of neurons, by "cycling" between these 22 data sets. The model was successfully validated against electrophysiological data not used in 23 model development, including experimentally observed subthreshold resonance characteristics. 24 Our model highlights kinetic differences in the h-current across species, with the unique 25 relationship between the model and experimental data allowing for a detailed investigation of the 26 relationship between the h-current and subthreshold resonance. 27 28 30 (Womelsdorf et al., 2014) within the six-layered neocortex stems from invasive and in vitro studies 31 in rodents and non-human primates. Whether or not such principles can be extended to human 32 neocortex remains speculative at best. Despite the significant transcriptomic convergence of 33 human and mouse neurons (Hodge et al., 2019), significant differences between human and rodent 34 cell-type properties exist. In vitro studies have identified differences between mouse and human 35 neurons in morphology (Mohan et al., 2015), dendritic integration (Beaulieu-Laroche et al., 2018; 36 Eyal et al., 2016), synaptic properties (Verhoog et al., 2013), and collective dynamics (McGinn and 37 Valiante, 2014; Molnár et al., 2008; Florez et al., 2013). However, less explored are the active 38 1 of 36 Manuscript submitted to eLife membrane properties of human cortical neurons, which together with their passive and synaptic 39 properties underlie oscillations which are of likely physiological relevance (Akam and Kullmann, 40 2014; Womelsdorf et al., 2014; Fries, 2005; Anastassiou et al., 2011; Hanslmayr et al., 2019; Vaz 41 et al., 2019). 42 Recently it has been shown that increased expression of hyperpolarization activated cation chan-43 nels (h-channels) contribute to the observed subthreshold resonance in supragranular layer human 44 pyramidal cells not seen in their rodent counterparts (Kalmbach et al., 2018). Such differential 45 expression of h-channels also appears to be present between superficial and deep layer neurons 46 of human cortex, with layer 5 (L5) pyramidal cells demonstrating a larger sag voltage mediated 47 65 et al., 2013; Beaulieu-Laroche et al., 2018) leads to two important questions for computational 66neuroscientists: in what settings is it appropriate to utilize rodent neuron models to glean insights 67 into the human brain, and when such approximations are u...

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