ADVANCED NEUROTECHNOLOGIES FOR BRAIN ACTIVITY MONITORING AND MODULATION

Evolution of silicon-based probes developed for large-scale neuronal recordings

Richárd Fiáth

Research Centre for Natural Sciences, Budapest, Hungary

Abstract: Penetrating neural probes were developed with the intention to record or to modulate the electrical activity of neurons located close to the implanted probe shank. First planar silicon-based devices designed for in vivo experiments contained only a few recording sites on a single shank monitoring the activity of a limited number of neurons, while the current technology used to fabricate state-of-the-art silicon probes allows the placement of over a thousand recording sites on a single or on multiple silicon shanks. This impressive engineering achievement was accomplished by the application of complementary metal-oxide-semiconductor (CMOS) technology which also resulted in a remarkable increase in the spatial resolution of these in vivo recordings. The resulting high-density, high-channel-count measurements usually contain the extracellular electrical activity of hundreds of neurons obtained simultaneously from multiple brain areas. This lecture gives a brief overview of the history of silicon-based neural probes, introduces their main features and highlights the main applications of these tools.

Application of high-density neural probes to explore the complex spatiotemporal dynamics of thalamocortical activity

Csaba Horváth^1,2, Mária Steinbach³, István Ulbert^1,3, Richárd Fiáth^1,3

¹Institute of Cognitive Neuroscience and Psychology, Research Centre for Natural Sciences, Budapest, Hungary 
²János Szentágothai Doctoral School of Neurosciences, Semmelweis University, Budapest, Hungary 
³ Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Budapest, Hungary 

Abstract: The application of recent developments in complementary metal-oxide semiconductor (CMOS) technology in invasive extracellular devices has led to innovative neural probes with an increased channel count and spatial resolution. These novel devices provide an opportunity to capture a much more detailed picture of the complex spatiotemporal dynamics of neuronal activity both at the cellular and network level. To demonstrate this, on the one hand, we present a large, publicly available dataset of extracellularly recorded single neurons (n=7126) obtained with a high-density single-shank silicon-based probe from the neocortex of anesthetized rats. Our preliminary findings indicate that spatial features extracted from the recorded high-resolution spike waveforms might aid a more reliable identification of cortical cell types. On the other hand, we used Neuropixels silicon probes to map thalamic activity of anesthetized rodents to locate propagating patterns of spiking activity during the active states of slow waves and to investigate their spatiotemporal features.

Transparent microECoGs for multimodal neuroimaging

Zs. Lantos^1,2, Á. Szabó^1,2, A. Zátonyi¹, F. Zs. Fedor^1,3,4,  M. Madarász^5,6, V. Danda⁷, B. Rózsa⁵, Z. Fekete¹

¹Research Group for Implantable Microsystems, Faculty of Information Technology and 
Bionics, Pázmány Péter Catholic University, Budapest, Hungary 
²Roska Tamás Doctoral School of Sciences and Technology, Pázmány Péter Catholic University, Budapest, Hungary 
³Microsystems Laboratory, Centre for Energy Research, Budapest, Hungary 
⁴Doctoral School of Chemical Engineering and Material Sciences, University of Pannonia, Veszprém, Hungary 
⁵Laboratory of 3D functional network and dendritic imaging, Institute of Experimental Medicine, Budapest, Hungary 
⁶János Szentágothai PhD Program of Semmelweis University, Budapest, Hungary 
⁷Qualia Labs, Inc.Dallas, TX 75252, USA

Abstract: Multimodal measurements have emerged as both functional and structural observation of  the brain is required to understand the complex mechanism of neuronal ensembles.  Electrophysiology is still used as a gold standard to interrogate brain activity, however, the  advent of new optical characterization tools like optogenetics, calcium imaging, or voltage-  sensitive dye imaging catalyzed the development of transparent neural interfaces that  enable the application of both modalities. This talk will summarize recent results of our  group that relied on the application of transparent microelectrocorticography arrays in  conjuction with intrinsic optical imaging and calcium imaging in anaesthetized and awake  mice and cats. Specifically, optical and electrical performance of polyimide/indium-tin oxide,  Parylene HT/indium-tin-oxide and thiol/ene-acrylate/gold electrodes will be demonstrated  in multimodal neuroimaging experiments. 

Compact optrode for in vivo opsin delivery, optical stimulation  and electrophysiological recordings in freely behaving animals 

Kirti Sharma^1,2,5, Zoë Jäckel^2,3,5, Artur Schneider^2,3, Oliver Paul^1,2,  Ilka Diester^2,3,4, Patrick Ruther^1,2

¹Department of Microsystems Engineering (IMTEK), University of Freiburg, Freiburg, Germany
²Cluster IMBIT/BrainLinks-BrainTools, University of Freiburg, Freiburg, Germany
³Faculty of Biology, Optophysiology, University of Freiburg, Freiburg, Germany
⁴Bernstein Center, University of Freiburg, Freiburg, Germany
⁵Equal contribution

Abstract: We present a multifunctional optrode that combines a silicon-based neural probe with an integrated microfluidic channel, and an optical glass fiber in a compact assembly. The tapered silicon probe has a maximum cross-section of 50 μm × 150 μm, and comprises an 11-μm-wide buried fluidic channel and 32 recording electrodes (diameter 30 μm). We applied the optrode to inject a viral vector carrying a ChR2-construct in the prefrontal cortex and subsequently photostimulated the transduced neurons for up to 9 weeks post-implantation in a freely moving rat. In addition, we simultaneously recorded neural activity from both the target and the adjacent regions. We observed minimal inflammation surrounding the recording shank and the electrophysiological recording quality was stable over time. With a total system weight of 0.97 g, our multifunctional optrode enables precise local injection and high spatial specificity while minimizing tissue damage.  

Funding: The research leading to these results has partly received funding through the DFG-funded Priority Programme SPP 1926 (Next Generation Optogenetics) under Grant Nos. RU 869/5-1 and DI 1908/6-1, the BrainLinks-BrainTools Cluster of Excellence funded by the German Research Foundation (Deutsche Forschungsgemeinschaft (DFG), Grant No. EXC 1086) and the Bernstein Award 2012 (Bundesministerium für Bildung und Forschung (BMBF), No. 01GQ2301). 