Search bioRxiv⌕ Search

bioRxiv · 10.1101/2021.11.22.469555

Characterizing the short-latency evoked response to intracortical microstimulation across a multi-electrode array

Abstract

ObjectivePersons with tetraplegia can use brain-machine interfaces to make visually guided reaches with robotic arms. Without somatosensory feedback, these movements will likely be slow and imprecise, like those of persons who retain movement but have lost proprioception. Intracortical microstimulation (ICMS) has promise for providing artificial somatosensory feedback. If ICMS can mimic naturally occurring neural activity, afferent interfaces may be more informative and easier to learn than interfaces that evoke unnaturalistic activity. To develop such biomimetic stimulation patterns, it is important to characterize the responses of neurons to ICMS. ApproachUsing a Utah multi-electrode array, we recorded activity evoked by single pulses, and short (~0.2 s) and long (~4 s) trains of ICMS at a wide range of amplitudes and frequencies. As the electrical artifact caused by ICMS typically prevents recording for many milliseconds, we deployed a custom rapid-recovery amplifier with nonlinear gain to limit signal saturation on the stimulated electrode. Across all electrodes after stimulation, we removed the remaining slow return to baseline with acausal high-pass filtering of time-reversed recordings. With these techniques, we could record ~0.7 ms after stimulation offset even on the stimulated electrode. Main resultsWe recorded likely transsynaptically-evoked activity as early as ~0.7 ms after single pulses of stimulation that was immediately followed by suppressed neural activity lasting 10-150 ms. Instead of this long-lasting inhibition, neurons increased their firing rates for ~100 ms after trains. During long trains, the evoked response on the stimulated electrode decayed rapidly while the response was maintained on non-stimulated channels. SignificanceThe detailed description of the spatial and temporal response to ICMS can be used to better interpret results from experiments that probe circuit connectivity or function of cortical areas. These results can also contribute to the design of stimulation patterns to improve afferent interfaces for artificial sensory feedback.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Sombeck, J., Heye, J., Kumaravelu, K., Goetz, S. M., Peterchev, A. V., Grill, W. M., Bensmaia, S. J., Miller, L. E.. 2021-11-23. Characterizing the short-latency evoked response to intracortical microstimulation across a multi-electrode array. https://doi.org/10.1101/2021.11.22.469555

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

A Mechanistic Account of Dedifferentiation in the Aging Visual System

To uncover the mechanisms of age-related dedifferentiation, we simulated neural degradation in a computational model of the ventral visual stream. Severing connections or adding noise, whether in inferotemporal cortex (IT) or upstream, reduced IT differentiation, indicating that dedifferentiation need not originate locally. Degrading peripheral V1, which preferentially drove place-selective IT neurons, selectively reduced place differentiation, a candidate mechanism for the stronger place dedifferentiation reported in aging.

neuroscience↗

Reusing pipettes in Patch-seq: a foundation for automated multimodal profiling

Patch-seq is a technique for single-cell multimodal characterization. It combines whole-cell electrophysiology, single-cell transcriptomics, and morphological reconstruction in single neurons. Patch-seq morphologies are a critical bridge among cell types, genes, physiology, and large-scale connectivity platforms such as EM connectomes and single-cell-resolution projectomes. However, patch-seq experimental complexity and operator dependence limit throughput. Automation could enable scalable Patch-seq but requires procedural adaptations, including detergent-based pipette cleaning, robotic nucleus extraction and collection. The impact of these automations on Patch-seq quality has not been systematically evaluated. Here, we show that each of these modifications preserves or improves key Patch-seq outcomes. Automated nucleus extraction performs comparably to, or better than, expert manual operation, preserving key RNA and morphological metrics. Detergent-cleaned, reused pipettes supported a viable sealing success rate across multiple cleaning cycles and preserved electrophysiological quality and transcriptomic yield without introducing excess contamination. Sonication effectively allows collection of nuclear material without damaging RNA and supports subsequent pipette cleaning and reuse. Enhanced automated sealing and break-in procedures increased throughput regardless of brain region, cell type or species. Together, these results validate the core procedural adaptations required for automated Patch-seq and establish a foundation for high-throughput, standardized multimodal single-cell characterization.

neuroscience↗

Development of direction selectivity in the Xenopus tadpole optic tectum and midbrain tegmentum

Detecting motion direction is a fundamental function performed by direction selective (DS) neurons. DS neurons in the optic tectum (superior colliculus in mammals) enable the tracking of moving objects. DS neurons of the accessory optic system support reflexive eye / head movements that stabilize gaze during self-motion. By developmental stage 48 (10 days postfertilization), Xenopus tadpoles display visually guided behaviors that require both types of DS neurons. Our previous work has shown that these two regions are not only functionally distinct but also follow different developmental programs. Here we characterized and compared how direction selectivity develops in both visual processing centers. Using in vivo electrophysiological recordings during moving bar visual stimulation, we measured DS synaptic inputs and spiking outputs in both regions across three key developmental stages of the retinotectal projection. Tegmental neurons were direction selective ab initio, and both input and output tuning remained stable across development. Tectal neurons were observed to receive DS inputs early, and their input selectivity also remained stable across development. However, their spiking output grew substantially more DS at the later developmental stage. This was due at least in part to a naturally occurring decrease in intrinsic excitability which preferentially dampened overall spike rates, but especially in response to the non-preferred direction of motion, thereby increasing direction selectivity. These results reveal distinct developmental trajectories in parallel visual pathways. Tegmental direction selectivity is established early and stays stable, whereas tectal output tuning sharpens during development through a decrease in intrinsic excitability.

neuroscience↗