Proximal and distal modulation of neural activity by spatially confined optogenetic activation with an integrated high-density probe

Sarah Libbrecht, Luis Hoffman, Marleen Welkenhuysen, Chris Van den Haute, Veerle Baekelandt, Dries Braeken, Sebastian Haesler
Journal of Neurophysiology, 120(1) 149-161, 2018

Optogenetic manipulations are widely used for investigating the contribution of genetically identified cell types to behavior. Simultaneous electrophysiological recordings are less common, although they are critical for characterizing the specific impact of optogenetic manipulations on neural circuits in vivo. This is at least in part because combining photostimulation with large-scale electrophysiological recordings remains technically challenging, which also poses a limitation for performing extracellular identification experiments. Currently available interfaces which guide light of the appropriate wavelength into the brain combined with an electrophysiological modality suffer from various drawbacks such as a bulky size, low spatial resolution, heat dissipation or photovoltaic artifacts. To address these challenges, we have designed and fabricated an integrated ultrathin neural interface with 12 optical outputs and 24 electrodes. We used the device to measure the effect of localized stimulation of pyramidal neurons in the anterior olfactory cortex, a paleocortical structure involved in olfactory processing. Our experiments in adult mice demonstrate that due to its small dimensions, our novel tool causes far less tissue damage than commercially available devices. Moreover, optical stimulation and recording can be performed simultaneously, with no measurable electrical artifact during optical stimulation. Importantly, optical stimulation can be confined to small volumes with approximately single cortical layer thickness. Finally, we find that even highly localized optical stimulation causes inhibition at more distant sites.

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