Biology subjects

Ruther, P.

Publications and source records attributed to Ruther, P..

9 recordsLinked to original sources

bioRxiv2026

Multichannel optical cochlear implants enable spectrally distinct auditory activity

When hearing fails, cochlear implants (CIs) restore auditory perception. Yet, coding of spectral information remains a bottleneck because each electrode broadly activates the auditory nerve. As light can be more conveniently confined, optical (o)CIs present an alternative. Here, we combined expression of the potent channelrhodopsin ChReef in spiral ganglion neurons (SGNs) with oCIs comprising 5-10 green LEDs in gerbils. This combination enabled systematic comparison of encoding intensity and spectral information by individual oCI channels to acoustic and electrical stimulation within a translationally feasible energy range. Recordings from the inferior colliculus (ICC) showed that ChReef aligned SGN light sensitivity with LED radiant fluxes: ICC activity had thresholds <200 nJ and reached a maximum equivalent to that achieved with 51 dB SPL pure tones. Multichannel oCIs enabled tonotopically ordered, spectrally distinct stimulation that more closely resembled acoustic stimulation than did electrical stimulation. Some LEDs elicited multiple spectral peaks at higher intensities. Linear discriminant analysis of ICC activity indicated improved channel discriminability for optical over electrical stimulation. In summary, ,micro-joule oCI-stimulation achieves improved spectral resolution over state-of-the-art electrical stimulation.

neuroscience↗

bioRxiv2026

Friend, not Foe: Lowered Tissue Reactivity to Long-Term Polyimide Implants

One of the biggest challenges for neurotechnology is the design of devices that are tolerated well by brain tissue, without sacrificing functionality and implantability. This study examined which design choices mitigate tissue damage and improve longevity, by varying probe features implanted in the cerebral cortex of mice. We report on a systematic, quantitative analysis of neuronal and inflammation markers across cortical depth. We implanted a total of 103 stiff silicon or flexible polyimide probes in 32 mice, varying their thicknesses and widths, which were either attached to the skull or not. A new, automated workflow to quantify immunohistochemical data examines: 1) the tissue loss caused by the implant, 2) the cortical neuronal density, and 3) the immune response expressed by astrocytic and microglial reaction. Flexible polyimide probes exhibited a clear advantage, with fewer lesions and weaker immune responses than stiff silicon probes. Furthermore, we observed a weaker influence of the shank cross-section. A cortical depth profile of immune reactivity revealed focal reactions at the device entry points in the superficial cortex and at the cortex-white matter boundary. This study gives important insights on optimizing device design parameters as well as surgical insights for improved tissue integration of intracortical electrode arrays.

bioengineering↗

bioRxiv2021

Intracortical probe arrays with silicon backbone and microelectrodes on thin polyimide wings enable long-term stable recordings in vivo

ObjectiveRecording and stimulating neuronal activity across different brain regions requires interfacing at multiple sites using dedicated tools while tissue reactions at the recording sites often prevent their successful long-term application. This implies the technological challenge of developing complex probe geometries while keeping the overall footprint minimal, and of selecting materials compatible with neural tissue. While the potential of soft materials in reducing tissue response is uncontested, the implantation of these materials is often limited to reliably target neuronal structures across large brain volumes. ApproachWe report on the development of a new multi-electrode array exploiting the advantages of soft and stiff materials by combining 7-m-thin polyimide wings carrying platinum electrodes with a silicon backbone enabling a safe probe implantation. The probe fabrication applies microsystems technologies in combination with a temporal wafer fixation method for rear side processing, i.e., grinding and deep reactive ion etching, of slender probe shanks and electrode wings. The wing-type neural probes are chronically implanted into the entorhinal-hippocampal formation in the mouse for in vivo recordings of freely behaving animals. Main resultsProbes comprising the novel wing-type electrodes have been realized and characterized in view of their electrical performance and insertion capability. Chronic electrophysiological in vivo recordings of the entorhinal-hippocampal network in the mouse of up to 104 days demonstrated a stable yield of channels containing identifiable multi-unit and single-unit activity outperforming probes with electrodes residing on a Si backbone. SignificanceThe innovative fabrication process using a process compatible, temporary wafer bonding allowed to realize new Michigan style probe arrays. The wing-type probe design enables a precise probe insertion into brain tissue and long-term stable recordings of unit activity due to the application of a stable backbone and 7-m-thin probe wings provoking locally a minimal tissue response and protruding from the glial scare of the backbone.

neuroscience↗

bioRxiv2021

Multifunctional optrode for opsin delivery, optical stimulation, and electrophysiological recordings in freely moving rats

ObjectiveOptogenetics involves delivery of light-sensitive opsins to the target brain region, as well as introduction of optical and electrical devices to manipulate and record neural activity, respectively, from the targeted neural population. Combining these functionalities in a single implantable device is of great importance for a precise investigation of neural networks while minimizing tissue damage. ApproachWe report on the development, characterization, and in vivo validation of 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 silicon probe comprises an 11-m-wide fluidic channel and 32 recording electrodes (diameter 30 m) on a tapered probe shank with a length, thickness, and maximum width of 7.5 mm, 50 m, and 150 m, respectively. The size and position of fluidic channels, electrodes, and optical fiber can be precisely tuned according to the in vivo application. Main resultsWith a total system weight of 0.97 g, our multifunctional optrode is suitable for chronic in vivo experiments requiring simultaneous drug delivery, optical stimulation, and neural recording. We demonstrate the utility of our device in optogenetics by injecting a viral vector carrying a ChR2-construct in the prefrontal cortex and subsequent photostimulation of the transfected neurons while recording neural activity from both the target and adjacent regions in a freely moving rat. Additionally, we demonstrate a pharmacological application of our device by injecting GABA antagonist bicuculline in an anesthetized rat brain and simultaneously recording the electrophysiological response. SignificanceOur triple-modality device enables a single-step optogenetic surgery. In comparison to conventional multi-step surgeries, our approach achieves higher spatial specificity while minimizing tissue damage. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=154 SRC="FIGDIR/small/441836v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@11fa19org.highwire.dtl.DTLVardef@3ab5b6org.highwire.dtl.DTLVardef@6fe1b2org.highwire.dtl.DTLVardef@14a7bb3_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2021

Neocortical rhythm entrainment by parvalbumin-positive interneurons across cortical layers

Neocortical interneurons provide inhibition responsible for organizing neuronal activity into brain oscillations that subserve cognitive functions such as memory, attention or prediction. However, little is known about the interneuronal contribution to the entrainment of neocortical oscillations within and across different cortical layers. Here, using layer-specific optogenetic stimulations with micro-Light-Emitting Diode ({micro}LED) arrays, directed toward parvalbumin-expressing (PV) interneurons in non-anesthetized awake mice, we found that supragranular layer stimulations of PV neurons were most efficient at entraining supragranular local field potential (LFP) oscillations at gamma frequencies ({gamma}: 25 - 80 Hz), whereas infragranular layer stimulation of PV neurons better entrained the LFP at delta ({delta}: 2 - 5 Hz) and theta ({theta}: 6 - 10 Hz) frequencies. At the level of neuronal action potential activity, we observed that supragranular neurons better followed the imposed PV stimulation rhythm than their infragranular counterparts at most frequencies when the stimulation was delivered in their respective layer. Moreover, the neuronal entrainment evoked by local stimulation could propagate across layers, though with a lesser impact when the stimulation occurs in deep layers, suggesting an orientation-selective propagation. These results establish a layer-based framework for oscillation to entrain the primary somatosensory cortex in awake conditions.

neuroscience↗

bioRxiv2021

Multichannel optogenetics combined with laminar recordings for ultra-controlled neuronal interrogation

Simultaneous large-scale recordings and optogenetic interventions hold the promise to decipher the fast-paced and multifaceted dialogue between neurons that sustains brain function. Here we developed unprecedentedly thin, cell-sized Lambertian side-emitting optical fibers and combined them with silicon probes to achieve high quality recordings and ultrafast multichannel optogenetic inhibition in freely moving animals. Our new framework paves the way for large-scale photo tagging and controlled interrogation of rapid neuronal communication in any combination of brain areas. HighlightsTo combine large-scale recordings with optical perturbation we have developed a number of new techniques such as thin optical side-emitting fibers, a fiber matrix connector for thin fibers, an electro-optical commutator for multiple thin fibers, an active patch cord, a flexible fiber bundle ribbon cable, and a modular multi-optrode implantation holder.

neuroscience↗

bioRxiv2020

Recording site placement on planar silicon-based probes affects neural signal quality: edge sites enhance acute recording performance

ObjectiveMultisite, silicon-based probes are widely used tools to record the electrical activity of neuronal populations. Several physical features of these devices (e.g. shank thickness, tip geometry) are designed to improve their recording performance. Here, our goal was to investigate whether the position of recording sites on the silicon shank might affect the quality of the recorded neural signal in acute experiments. ApproachNeural recordings obtained with five different types of high-density, single-shank, planar silicon probes from anesthetized rats were analyzed. Wideband data were filtered (500 - 5000 Hz) to extract spiking activity, then various quantitative properties (e.g. amplitude distribution of the filtered potential, single unit yield) of the recorded cortical and thalamic activity were compared between sites located at different positions of the silicon shank, focusing particularly on edge and center sites. Main resultsEdge sites outperformed center sites: mean values of the examined properties of the spiking activity were in most cases higher for edge sites (~94%, 33/35) and a large fraction of these differences were also statistically significant (~45%, 15/33) with effect sizes ranging from small to large. Although the single unit yield was similar between site positions, the difference in signal quality was remarkable in the range corresponding to high-amplitude spikes. Furthermore, the advantage of edge sites slightly decreased for probes having a narrower shank. SignificanceThe better signal quality on edge sites might be the result of the reduced shielding effect of the silicon shank providing a larger field of view for edge sites to detect spikes, or the less tissue damage caused near the edges of the shank. Our results might aid the design of novel neural implants in enhancing their recording performance by identifying more efficient recording site placements.

neuroscience↗

bioRxiv2020

Hearing restoration by a low-weight power-efficient multichannel optogenetic cochlear implant system

In case of deafness, electrical cochlear implants (eCIs) bypass dysfunctional or lost hair cells by direct stimulation of the auditory nerve. However, spectral selectivity of eCI sound coding is low as the wide current spread from each electrode activates large sets of neurons along the tonotopic axis. As light can be better confined in space, optical cochlear implants (oCIs) promise to overcome this shortcoming of eCIs. This requires appropriate sound processing and control of multiple microscale emitters. Here, we describe the development, characterisation, and application of a preclinical low-weight and wireless LED-based multichannel oCI system for hearing restoration and its companion to its sister eCI system. The head-worn oCI system enabled deafened rats to perform a locomotion task in response to acoustic stimulation proving the concept of multichannel optogenetic hearing restoration in rodents.

neuroscience↗

bioRxiv2018

Why not record from every channel with a CMOS scanning probe?

It is an uninformative truism to state that the brain operates at multiple spatial and temporal scales, each with each own set of emergent phenomena. More worthy of attention is the point that our current understanding of it cannot clearly indicate which of these phenomenological scales are the significant contributors to the brains function and primary output (i.e. behaviour). Apart from the sheer complexity of the problem, a major contributing factor to this state of affairs is the lack of instrumentation that can simultaneously address these multiple scales without causing function altering damages to the underlying tissue. One important facet of this problem is that standard neural recording devices normally require one output connection per electrode. This limits the number of electrodes that can fit along the thin shafts of implantable probes generating a limiting balance between density and spread. Sharing a single output connection between multiple electrodes relaxes this constraint and permits designs of ultra-high density probes. Here we report the design and in-vivo validation of such a device, a complementary metal-oxide-semiconductor (CMOS) scanning probe with 1344 electrodes; the outcome of the European research project NeuroSeeker. We show that this design targets both local and global spatial scales by allowing the simultaneous recording of more than 1000 neurons spanning 7 functional regions with a single shaft. The neurons show similar recording longevity and signal to noise ratio to passive probes of comparable size and no adverse effects in awake or anesthetized animals. Addressing the data management of this device we also present novel visualization and monitoring methods. Using the probe with freely moving animals we show how accessing a number of cortical and subcortical brain regions offers a novel perspective on how the brain operates around salient behavioural events. Finally, we compare this probe with lower density, non CMOS designs (which have to adhere to the one electrode per output line rule). We show that an increase in density results in capturing neural firing patterns, undetectable by lower density devices, which correlate to self-similar structures inherent in complex naturalistic behaviour. To help design electrode configurations for future, even higher density, CMOS probes, recordings from many different brain regions were obtained with an ultra-dense passive probe.

neuroscience↗