Biology subjects

Fiath, R.

Publications and source records attributed to Fiath, R..

10 recordsLinked to original sources

bioRxiv2026

Polymer-based flexible multi-shank probes for simultaneous intracortical microstimulation and two-photon calcium imaging

Intracortical microstimulation is an essential tool for basic neuroscience and sensory restoration, yet the spatiotemporal effects of advanced multielectrode stimulation strategies on cortical networks remain poorly understood. This study presents a versatile experimental platform featuring polymer-based, flexible multi-shank electrode arrays integrated with a custom high-density neurostimulator. The polyimide penetrating probes contain densely spaced iridium oxide microelectrodes on thin, flexible shanks with sharp tips designed to minimize mechanical mismatch, tissue damage, and brain dimpling. The system was validated in transgenic GCaMP6 mice through simultaneous two-photon calcium imaging and electrical stimulation in layer 2/3 of the visual cortex. Monopolar stimulation reliably evoked robust, parameter-dependent neuronal activation, with neuronal recruitment increasing as a function of current intensity and pulse duration. Bipolar stimulation produced activation patterns distinct from monopolar stimulation, with neuronal responses that were more spatially confined when bipolar electrodes were positioned in close proximity. Furthermore, static current steering--implemented by varying the current ratio between the selected electrode pair--successfully shifted the centroid of activated neuronal populations, enabling fine spatial control over the site of activation. The developed platform provides a flexible framework for investigating local neuronal responses to complex electrical stimulation paradigms, facilitating the development of neural prostheses with higher spatial precision.

neuroscience↗

bioRxiv2025

Focal infrared stimulation modulates somatosensory cortical activity in mice: evidence for TRPV1 ion channel involvement

Infrared neural stimulation (INS) is a promising approach for minimally invasive modulation of neuronal activity, yet its cellular and molecular mechanisms in the intact brain remain incompletely understood. Here, we investigated focal INS in the somatosensory cortex of anesthetized mice using high-density Neuropixels recordings combined with histological analysis. Continuous-wave and pulsed (500 Hz) infrared illumination elicited robust modulation of cortical activity, with approximately half of recorded neurons exhibiting either increased or suppressed firing. The modulatory effects of stimulation were comparable across cortical layers and neuron types. While both stimulation modes were effective, continuous-wave stimulation typically produced stronger changes in firing rates and network dynamics than pulsed illumination. To explore molecular contributions, we compared responses in wild-type and TRPV1 knockout mice. Neuronal responses to INS were significantly reduced in knockout animals, indicating a key role for TRPV1 channels. We also observed layer- and neuron-type-specific differences in firing rate modulation between wild-type and knockout animals. Histological analysis confirmed that TRPV1-expressing neurons are distributed throughout cortical layers, supporting their involvement in the observed responses. These findings provide direct evidence that TRPV1 contributes to INS-evoked cortical activity and advance our understanding of the mechanisms underlying infrared neuromodulation. This work lays a foundation for the future use of infrared light as a precise and minimally invasive tool for cortical circuit manipulation.

neuroscience↗

bioRxiv2025

Local infrared stimulation modulates spontaneous cortical slow wave dynamics in anesthetized rats

Cortical slow waves are hallmark oscillations of deep sleep and certain anesthetic conditions, yet the neurobiological mechanisms controlling their dynamics remain incompletely understood. Here, we investigated the effects of local near-infrared (NIR) stimulation on slow-wave activity in ketamine/xylazine-anesthetized rats. Using a silicon-based multimodal optrode, we simultaneously delivered NIR light and recorded local field potentials (LFPs) and multi-unit activity (MUA) across cortical layers in the primary somatosensory (S1Tr) and parietal association (PtA) cortices. NIR stimulation induced local tissue heating, resulting in reproducible and reversible changes in the properties of slow waves. Specifically, up-state durations were shortened, down-states prolonged, and MUA amplitudes during up-states increased, with steeper slopes at state transitions, indicative of enhanced neuronal synchronization. LFP amplitude and spectral changes varied across cortical regions: PtA exhibited increased slow wave (0.5 - 2 Hz) and high delta (2 - 4 Hz) band activity, while S1Tr showed a trend toward reduction. Our findings demonstrate that local infrared stimulation can reliably modulate cortical slow-wave dynamics, likely through temperature-mediated changes in neuronal excitability. This approach provides a minimally invasive method for precise, local manipulation of cortical network activity and offers new insights into the biophysical regulation of slow oscillations.

neuroscience↗

bioRxiv2025

Optimal inter-electrode distances for maximizing single unit yield per electrode in neural recordings

State-of-the-art high-density multielectrode arrays enable the recording of simultaneous spiking activity from hundreds of neurons. Although significant efforts have been dedicated to enhancing neural recording devices and developing more efficient sorting algorithms, there has been relatively less focus on the allocation of microelectrodes--a factor that undeniably affects spike sorting effectiveness and ultimately the total number of detected neurons. Here, we systematically examined the relationship between optimal electrode spacing and spike sorting efficiency by creating virtual sparser layouts from high-density recordings through spatial downsampling. We assessed spike sorting performance by comparing the quantity of well-isolated single units per electrode in sparse configurations across various brain regions (neocortex and thalamus) and species (rat, mouse, and human). Enabling the theoretical estimation of optimal electrode arrangements, we complement experimental results with a geometrical modeling framework. Contrary to the general assumption that higher electrode density inherently leads to more efficient sorting, both our theoretical and experimental results reveal a clear optimum for electrode spacing specific to species and regions. We demonstrate that carefully choosing optimal electrode distances could yield a total of 1.7 to 3 times increase in spike sorting efficiency. These findings emphasize the necessity of species- and region-specific microelectrode design optimization.

neuroscience↗

bioRxiv2024

TRPV3 channel activity helps cortical neurons stay active during fever

Fever raises body temperature (Tb) from [~]37 {degrees}C to beyond 38.4 {degrees}C to combat pathogens. While generally well tolerated below 40 {degrees}C, in rare cases fever can abnormally elevate neural activity and induce seizures in neurotypical children aged 2-5 years. This study investigates the mechanisms by which neuronal activity is maintained and stabilized during exposure to fever-range temperatures. Recordings of layer (L)4-evoked spiking in L2/3 pyramidal neurons (PNs) of mouse somatosensory cortex revealed four outcomes as temperature increased from 30{degrees}C to 36 {degrees}C and 39 {degrees}C (fever-range): neurons remained inactive, stayed active, ceased activity, or initiated activity. Roughly equal proportions of neurons ceased or initiated spiking, making the subset of "STAY" PNs, those that remain active across temperatures, crucial for maintaining stable cortical output. STAY PNs were more prevalent at younger postnatal ages. Their firing stability was supported by a distinct ion channel composition, including the thermosensitive channel TRPV3, which enables continued spiking by adjusting depolarization to meet spike threshold. Intracellular blockade of TRPV3, but not TRPV4, significantly reduced the proportion of STAY PNs and suppressed spiking at 39 {degrees}C. Moreover, in Trpv3-/-mice, temperature increases to 39 {degrees}C reduced both spiking and postsynaptic potential amplitude, and these mice exhibited a delayed seizure onset. Together, these findings suggest that TRPV3 contributes to the preservation of cortical activity during fever.

neuroscience↗

bioRxiv2023

DREDge: robust motion correction for high-density extracellular recordings across species

High-density microelectrode arrays (MEAs) have opened new possibilities for systems neuroscience in human and non-human animals, but brain tissue motion relative to the array poses a challenge for downstream analyses, particularly in human recordings. We introduce DREDge (Decentralized Registration of Electrophysiology Data), a robust algorithm which is well suited for the registration of noisy, nonstationary extracellular electrophysiology recordings. In addition to estimating motion from spikes in the action potential (AP) frequency band, DREDge enables automated tracking of motion at high temporal resolution in the local field potential (LFP) frequency band. In human intraoperative recordings, which often feature fast (period <1s) motion, DREDge correction in the LFP band enabled reliable recovery of evoked potentials, and significantly reduced single-unit spike shape variability and spike sorting error. Applying DREDge to recordings made during deep probe insertions in nonhuman primates demonstrated the possibility of tracking probe motion of centimeters across several brain regions while simultaneously mapping single unit electrophysiological features. DREDge reliably delivered improved motion correction in acute mouse recordings, especially in those made with an recent ultra-high density probe. We also implemented a procedure for applying DREDge to recordings made across tens of days in chronic implantations in mice, reliably yielding stable motion tracking despite changes in neural activity across experimental sessions. Together, these advances enable automated, scalable registration of electrophysiological data across multiple species, probe types, and drift cases, providing a stable foundation for downstream scientific analyses of these rich datasets.

neuroscience↗

bioRxiv2023

Propagating population activity patterns during spontaneous slow waves in the thalamus of rodents

Slow waves (SWs) represent the most prominent electrophysiological events in the thalamocortical system under anesthesia and during deep sleep. Recent studies have revealed that SWs have complex spatiotemporal dynamics and propagate across neocortical regions. However, it is still unclear whether neuronal activity in the thalamus exhibits similar propagation properties during SWs. Here, we report propagating population activity in the thalamus of ketamine/xylazine-anesthetized rats and mice visualized by high-density silicon probe recordings. In both rodent species, propagation of spontaneous thalamic activity during up-states was most frequently observed in dorsal thalamic nuclei such as the higher order posterior (Po), lateral posterior (LP) or laterodorsal (LD) nuclei. The preferred direction of thalamic activity spreading was along the dorsoventral axis, with over half of the up-states exhibiting a gradual propagation in the ventral-to-dorsal direction. Furthermore, simultaneous neocortical and thalamic recordings demonstrated that there is a weak but noticeable interrelation between propagation patterns observed during cortical up-states and those displayed by thalamic population activity. In addition, using chronically implanted silicon probes, we detected propagating activity patterns in the thalamus of naturally sleeping rats during slow-wave sleep. However, in comparison to propagating up-states observed under anesthesia, these propagating patterns were characterized by a reduced rate of occurrence and a faster propagation speed. Our findings suggest that the propagation of spontaneous population activity is an intrinsic property of the thalamocortical network during synchronized brain states such as deep sleep or anesthesia. Additionally, our data implies that the neocortex may have partial control over the formation of propagation patterns within the dorsal thalamus.

neuroscience↗

bioRxiv2021

Huygens synchronization of medial septal pacemaker neurons generates hippocampal theta oscillation

Episodic learning and memory retrieval are critically dependent on a hippocampal 4-12 Hz oscillatory clock signal, the theta oscillation. This clock is largely externally paced, by a network of GABAergic neurons in the medial septum (MS). Theoretical studies suggested a range of hypotheses how this network may achieve theta synchrony; however, experimental evidence is still lacking. By recording multiple single MS neurons and hippocampal local field potential oscillations simultaneously, with both acute and chronically implanted silicon probes, we show that MS pacemaker units oscillate at individual frequencies within the theta range in rodents. Synchronization of MS neuron frequencies, accompanied by an elevation of firing rates, was found to parallel hippocampal theta formation in multiple rodent model systems. This suggests a general mechanism for theta synchronization, akin to the synchronization of weakly coupled pendulum clocks observed by Huygens in the 17th century. We optogenetically identified the MS pacemaker units as parvalbumin-expressing GABAergic neurons, while the previously enigmatic MS glutamatergic neurons were mostly theta-activated non-rhythmic cells. Our data were consistent with a network model of partially connected single-compartment inhibitory pacemaker neurons, in which synchronization and de-synchronization in the frequency domain upon waxing and waning tonic excitatory drive was sufficient to toggle MS network output between theta and non-theta states. These results provide experimental and theoretical support to a frequency-synchronization mechanism for pacing hippocampal theta, which may serve as an inspirational prototype for the countless examples of synchronization processes in the central nervous system from Nematoda to Anthropoda to Chordate and Vertebrate phyla.

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↗

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↗