Biology subjects

Berg, R. W.

Publications and source records attributed to Berg, R. W..

16 recordsLinked to original sources

bioRxiv2026

Spinal rotational dynamics orchestrate locomotor recovery

Locomotion is one of the most essential functions of the nervous system, yet the principles that generate it and how it might be restored after spinal cord injury remain unresolved. Walking is possible even after complete spinal cord injury and a traditional assumption is that this activity emerges from modular flexor-extensor transitions driven by somatosensory feedback. To test this assumption, we recorded bilateral motor unit activity from sixteen flexor/extensor hindlimb muscles in awake cats walking on a treadmill. We found that spinal motor populations operate according to a fundamentally different principle. Rather than alternating between flexion and extension, population activity continuously rotated through all phases of the locomotor cycle within a low-dimensional neural manifold. This rotational organisation persisted after complete spinal cord injury, revealing the preservation of a cyclic attractor despite substantial alterations in motor outputs. Computational modeling further indicated that locomotor activity was more consistent with an autonomous regime than with somatosensory-driven control. These findings suggest that locomotor recovery after complete spinal cord injury reflects the preservation of an intrinsic spinal attractor and that somatosensory feedback contributes to, rather than generates, the locomotor rhythm. More broadly, they establish rotational population dynamics as a fundamental principle of spinal locomotor recovery.

neuroscience↗

bioRxiv2026

Cue-guided performance is disrupted during pedunculotegmental-induced motor arrest

Optogenetic stimulation of the rostral pedunculotegmental nucleus (PTg) induces global motor arrest, but it remains unclear whether this is merely a suppression of motor activity or a broader disruption of brain processes required to guide action. We developed a visuospatial cue task for rats, to test if sensory information presented during PTg-induced arrest can guide later responses. Here, we show that optogenetic stimulation during cue presentation reduces accuracy to chance level. By moving stimulation to only before or only after the cue, we found that performance was only affected when stimulation and cue presentation overlapped, that rats recover cue-guided behavior almost immediately at the end of stimulation, and that stimulation does not appear to abolish responses based on cue information acquired before arrest. These findings indicate that stimulation of the rostral PTg does not only pause motor output but transiently disrupts the ability to process and use cue information effectively.

neuroscience↗

bioRxiv2025

Neural manifolds that orchestrate walking and stopping

Walking, stopping and maintaining posture are essential motor behaviors, yet the underlying neural processes remain poorly understood. Here, we investigate neural activity behind locomotion and its walk-to-stop transition. Based on a new theory of the lumbar spinal cord1, 2 we propose and predict that spinal population activity contains limit cycle dynamics to drive walking and fixed-point attractors for stopping. To test these predictions we record neural activity in lumbar cord of freely moving rats using Neuropixels probes3. To control stopping, we stimulate a brainstem nucleus, known to induce motor arrest4-7. We find: During locomotion, the population activity of lumbar spinal neurons exhibits rotational dynamics8-10. These dynamics unfold within a low-dimensional locomotor manifold11, 12, a looping set of trajectories that serves as the repeating signature of locomotion, that also behaves as a limit-cycle attractor. Shortly before stopping, the neural state rapidly changes from the locomotor manifold to a postural fixed point attractor. When kicking the state out of the fixed point using perturbations it shifts to a nearby albeit different fixed point. Repeated stoppings form a local quasi-continuum of fixed points representing various poses - i.e. a postural manifold. These observations are in agreement with our theory, which further indicates the mechanistic roles for subpopulations of spinal interneurons for controlling walking and stopping. Besides explaining the data, our theory makes further predictions to be tested in future experiments.

neuroscience↗

bioRxiv2024

Soft biocompatible polymer optical fiber tapers for implantable neural devices

Optical fibers are between the most common implantable devices for delivering light in the nervous system for optogenetics and infrared neural stimulation applications. Tapered optical fibers, in particular, can offer homogeneous light delivery to a large volume and spatially resolved illumination compared to standard flat-cleaved fibers while being minimally invasive. However, the use of tapers for neural applications has up to now been limited to silica optical fibers, whose large Youngs modulus can cause detrimental foreign body response in chronic settings. Here, we present the fabrication and optimization of tapered fiber implants based on polymer optical fibers (POFs). After numerically determining the optimal materials and taper geometry, we fabricated two types of POFs by thermal fiber drawing. The fabrication of the taper was achieved by chemical etching of the fibers, for which several solvents previously reported in literature have been tested. The influence of different parameters on the etching process and on the quality of the obtained tapers was also investigated. The large illumination volume of the produced high-quality taper-based implants was finally tested in vitro in a brain phantom.

neuroscience↗

bioRxiv2024

Lifting the degeneracy of optical fiber neural interfaces for optogenetics and electrophysiology by using axialtrodes

Modulating and recording neuronal activity are essential for probing brain function and developing therapies for neurological disorders. However, conventional flat-end optical fibers--widely used for deep brain access-- interact with neural tissue only at their distal tip, limiting spatial resolution across brain layers. To overcome this constraint, we introduce the microfluidic axialtrode: a soft, multimodal neural interface created by controllably angle-cleaving a thermally drawn, multimaterial optical fiber integrated with multiple metal electrodes and microfluidic channels. We demonstrate in vivo that this design enables spatially distributed optogenetics, multisite electrophysiological recording, and targeted drug delivery along the fibers axis, allowing simultaneous interaction with multiple neuronal layers. The axial configuration increases the functional interface with brain tissue, while the soft polymer construction and reduced cross-sectional footprint significantly suppress the inflammatory response compared to conventional silica fibers. Integration with a 3D-printed scaffold, fabricated from FDA-approved biocompatible resin, provides mechanical stability and compatibility with standard experimental hardware. The monolithic integration of these features positions the axialtrode as a scalable and versatile platform for next-generation neural interfacing.

neuroscience↗

bioRxiv2024

Spatial and network principles behind neural generation of locomotion

Generation of locomotion is a fundamental function of the spinal cord, yet the underlying principles remain unclear. In particular, the relationship between neuronal cell types, networks and functions has been difficult to establish1,2. Here, we propose principles by which functions arise primarily from spatial features of the cord. First, we suggest that projections of distinct cell types constitute an asymmetrical "Mexican hat" topology, i.e. local excitation and surrounding inhibition with dissimilar length of projection along the rostro-caudal axis. Second, this projection topology constitutes the mechanism of rhythm- and pattern generation of mammalian locomotion. Third, the role of segregation of cell types in the transversal plane is for descending fibers to find appropriate targets. Modulation of these targets allows control of motor activity by adjusting the symmetry of the projection topology. We extract these principles via a model of the mouse spinal cord, where networks are constructed by probabilistic sampling of synaptic connections from cell-specific projection patterns, which are based on previous studies3, 4. The cell-type distributions are derived from single-cell RNA sequencing combined with spatial transcriptomics5. We find that essential aspects of locomotion are readily reproduced and controlled without requiring parameter optimization, and several experimental observations can now be explained mechanistically. Further, two main features are predicted: propagating bumps of neural activity during rhythmical activity and formation of static bumps during arrest and posture. Besides linking cell types, structure and function, we propose our approach as a new theoretical framework for motor control.

neuroscience↗

bioRxiv2024

In vivo evaluation of thermally drawn biodegradable optical fibers as brain neural interfaces

Optical fiber technology has a critical role in modern neuroscience towards understanding the complex neuronal dynamics within the nervous system. In this study, we manufactured amorphous thermally drawn poly D, L-lactic acid (PDLLA) optical fibers in different diameters. These fibers were then implanted into the lateral posterior (LP) region of the mouse brain for 4 months, allowing us to assess their degradation characteristics. The gradual dissolution of the implanted PDLLA optical fibers in the brain was confirmed by optical microscope and scanning electron microscopy (SEM), molecular weight measurements, and light transmission spectroscopy. The results indicate that the degradation rate was mainly pronounced during the first week. Degradation after 4 months resulted in the formation of micropores on the surface of the implanted fiber within the gray matter region of the brain. Moreover, the current PDLLA optical fiber implant offers efficient light transmission in the short-wavelength near-infrared (SW-NIR) range. SW-NIR enables deeper tissue penetration and reduced light scattering, making it ideal for optogenetics and functional imaging with therapeutic potential in neurological disorders. We believe that the provided PDLLA optical fiber in this study constitutes a promising candidate for the development of next-generation biocompatible, soft, and biodegradable bi-directional neural interfaces

bioengineering↗

bioRxiv2024

Mid-infrared photoacoustic brain imaging enabled by cascaded gas-filled hollow-core fiber lasers

SignificanceExtending the photoacoustic microscopy (PAM) into the mid-infrared (MIR) molecular fingerprint region constitutes a promising route towards label-free imaging of biological molecular structures. Realizing this objective requires a high-energy nano-second MIR laser source. However, existing MIR laser technologies are limited to either low pulse energy or free-space structure which is sensitive to environmental conditions. Fiber lasers are promising technologies for PAM for their potential of offering both high pulse energy and robust performance against environmental conditions. However, MIR high energy fiber laser has not yet been used for PAM because it is still at the infant research stage. AimWe aim to employ the emerging gas-filled anti-resonant hollow-core fiber (ARHCF) laser technology for MIR-PAM for the purpose of imaging myelin-rich regions in a mouse brain. ApproachThis laser source is developed with a [~]2.75 J high-pulse-energy nano-second laser at 3.4 m, targeting the main absorption band of myelin sheaths, the primary chemical component of axons in the central nervous system. The laser mechanism relies on two-orders gas-induced vibrational stimulated Raman scattering (SRS) for nonlinear wavelength conversion, starting from a 1060 nm pump laser to 1409 nm through the 1st order Stokes generation in the nitrogen-filled 1st stage ARHCF, then, from 1409 nm to 3.4 m through the 2nd stage hydrogen-filled ARHCF. ResultsThe developed Raman laser was used for the first time for transmission-mode MIR-PAM of mouse brain regions containing rich myelin structures. ConclusionsThis work pioneers the potential use of high-energy and nano-second gas-filled ARHCF laser source to MIR-PAM, with a first attempt to report this kind of fiber laser source for PAM of lipid-rich myelin regions in a mouse brain. The proposed ARHCF laser technology is also expected to generate high-energy pulses at the ultraviolet (UV) region, which can significantly improve the lateral resolution of the PAM.

neuroscience↗

bioRxiv2023

In vivo multi-site electrophysiology enabled by flexible optrodes towards bi-directional spinal cord interrogation

Optical neural interfaces combining optogenetics and electrophysiology have been demonstrated as powerful tools for distinguishing the causal roles of neural circuits in the nervous system. Functional optrodes for multipoint stimulation and recording have already been demonstrated in the brain. However, soft and flexible multimodal optrodes for the purpose of probing the spinal cord have remained undeveloped. Here, we present the design and fabrication of a novel optrode for multi-site optical stimulation and electrical recording in the spinal cord by combining optical fiber drawing of polymer material, laser micromachining, and integration of tungsten microelectrodes in a monolithic fiber-based structure. The results from space-resolved scattering measurements, electrochemical impedance spectroscopy, and an acute in vivo electrophysiology experiment in an anesthetized rodent suggest this probe as a potential novel interface, which can serve as a part of therapeutic strategies against neurological conditions and injury in the spinal cord.

neuroscience↗

bioRxiv2023

Arrest of movement induced by Pedunculopontine-stimulation obstructs hippocampal theta rhythm

Complete movement arrest has recently been reported to be induced in rodents by optogenetic stimulation of a subpopulation within the pedunculopontine nucleus (PPN). This evoked arrest appears conspicuously similar to freezing behavior often seen as a fear response in prey animals but could also be akin to the freezing of gait, which is a symptom of Parkinsons disease. This introduces two perspectives on the functional roles of this sub-region: A hub for orchestrating fear-related responses or an omnipotent halting mechanism devoid of emotional components. To better understand this phenomenon and its cognitive component, we engage the distinct electrical brain activity, the hippocampal theta rhythm. This rhythm has a well-described contextual association between various aspects of cognition and behavior. It is prominent during locomotor activity in rodents and immobile yet aroused states like behavioral freezing. We recorded the electrical activity in the hippocampus of rats while walking and being arrested by PPN stimulation. A clear obstruction of the ongoing theta activity was associated with the motor arrest. The timescale of movement arrest was less than 200 ms, similar to the obstruction of the theta rhythm. Since, anxiety, fear, and behavioral freezing are associated with hippocampal theta rhythm, which we did not see during PPN stimulation, we suggest the induced motor arrest occurs without an associated emotional component.

neuroscience↗

bioRxiv2022

Opsin-free optical neuromodulation and electrophysiology enabled by a soft monolithic infrared multifunctional neural interface

Controlling neuronal activity with high spatial resolution using multifunctional and minimally invasive neural interfaces constitutes an important step towards developments in neuroscience and novel treatments for brain diseases. While infrared neuromodulation is an emerging technology for controlling the neuronal circuitry, it lacks soft implantable monolithic interfaces capable of simultaneously delivering light and recording electrical signals from the brain while being mechanically brain-compatible. Here, we have developed a soft fibre-based device based on high-performance thermoplastics which are >100-fold softer than silica glass. The presented fibre-implant is capable of safely neuromodulating the brain activity in localized cortical domains by delivering infrared laser pulses in the 2 m spectral region while recording electrophysiological signals. Action and local field potentials were recorded in vivo in adult rats while immunohistochemical analysis of the tissue indicated limited microglia and monocytes response introduced by the fibre and the infrared pulses. We expect our devices to further enhance infrared neuromodulation as a versatile approach for fundamental research and clinically translatable therapeutic interventions.

neuroscience↗

bioRxiv2021

Movement is governed by rotational population dynamics in spinal motor networks

Although the generation of movements is a fundamental function of the nervous system, the underlying neural principles remain unclear. Since flexor- and extensor-muscles alternate during rhythmic movements like walking, it is often assumed that the responsible neural circuitry is similarly displaying alternating activity. Here, we present ensemble-recordings of neurons in the lumbar spinal cord that indicate that, rather than alternating, the population is performing a low-dimensional "rotation" in neural space, in which the neural activity is cycling through all phases continuously during the rhythmic behavior. The radius of rotation correlates with the intended muscle force and a perturbation of the low-dimensional trajectory can modify the motor behavior. Since existing models of spinal motor control offer an inadequate explanation of rotation, we propose a new theory of neural generation of movements from which this and other unresolved issues, such as speed regulation, force control, and multi-functionalism, are readily explained.

neuroscience↗

bioRxiv2020

What are the gray and white matter volumes of the human spinal cord?

The gray matter of the spinal cord is the seat of somata of various types of neurons devoted to the sensory and motor function of the limbs and trunk. The volume of the spinal gray matter is an indicator of the local neuronal processing and this can decrease due to atrophy associated with degenerative diseases and injury. Nevertheless, the absolute volume of the human spinal cord has rarely been reported, if ever. Here, we use high-resolution magnetic resonance imaging, with a cross-sectional resolution of 50 x 50m2, to estimate the total gray and white matter volume of two post mortem human spinal cords. Segregation of gray and white matter was accomplished using deep learning image segmentation. The gray and white matter volumes were found to be 2.87 and 11.33 ml, respectively for a female and 3.55 and 19.33 ml, respectively for a male. The gray and white matter profiles along the vertebral axis were found to be strikingly similar and the volumes of the cervical, thoracic and lumbosacral sections were almost equal. NEW AND NOTEWORTHYHere, we combine high field MRI (9.4T) and deep learning for a post-mortem reconstruction of the gray and white matter in a human spinal cord. We report a minuscule total volume of the gray matter of 2.87 ml for a female and 3.55 ml for a male. The gray matter volumes are unexpectedly small. For comparison, these volumes correspond approximately to the distal digital of the little finger.

neuroscience↗

bioRxiv2020

Vasculature-staining with lipophilic dyes in tissue-cleared brains assessed by deep learning

Visualization of the vasculature in three dimensions (3D) has become attractive, particularly in stroke models. 3D-reconstruction is aided by tissue-clearing, where the transparency allows imaging of fluorescent probes in deeper structures. The vasculature is commonly stained by fluorescent lipophilic dyes that are incorporated into the wall during transcardial perfusion. Nevertheless, tissue clearing involves extracting the light-scattering lipids, and hence also the lipid-appended dyes. The wash-out likely depends on dye and its aldehyde-fixability. Fixation secures cross-linking to proteins and hence retainment in the tissue. However, the compatibility of various types of dyes is largely unknown. We tested and compared 9 different dyes for vasculature staining and tolerance to lipid clearing, which was quantified using deep learning image segmentation. Among the dyes, we found a subset that is both cost-effective and compatible with tissue lipid clearing. We suggest these dyes will provide a valuable tool for future investigations. HighlightsO_LISize, alkyl-chains and aldehyde-fixable groups improve dye retention and performance. C_LIO_LICost-effective dyes in specific liposomes result in optimal vessel staining. C_LIO_LISP-DiIC18 is compatible with CLARITY and BrainFilm and advantageous for most studies. C_LIO_LIWe recommend, SP-DiI and R18, cost-effective dyes, for vessel-painting with CLARITY. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=103 SRC="FIGDIR/small/099705v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@2f7eborg.highwire.dtl.DTLVardef@e272a4org.highwire.dtl.DTLVardef@d48a29org.highwire.dtl.DTLVardef@1ba9781_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2018

Decoupling of timescales reveals sparse convergent CPG network in the adult spinal cord

During the generation of rhythmic movements, most spinal neurons receive an oscillatory synaptic drive. The neuronal architecture underlying this drive is unknown, and the corresponding network size and sparseness have not yet been addressed. If the input originates from a small central pattern generator (CPG) with dense divergent connectivity, it will induce correlated input to all receiving neurons, while sparse convergent wiring will induce a weak correlation, if any. Here, we use pairwise recordings of spinal neurons to measure synaptic correlations and thus infer the wiring architecture qualitatively. A strong correlation on a slow timescale implies functional relatedness and a common source, which will also cause correlation on fast timescale due to shared synaptic connections. However, we consistently find marginal coupling between slow and fast correlations regardless of neuronal identity. This suggests either sparse convergent connectivity or a CPG network with recurrent inhibition that actively decorrelates common input.

neuroscience↗

bioRxiv2017

Advances And Perspectives In Tissue Clearing Using CLARITY

CLARITY is a tissue clearing method, which enables immunostaining and imaging of large volumes for 3Dreconstruction. The method was initially time-consuming, expensive and relied on electrophoresis to remove lipids to make the tissue transparent. Since then several improvements and simplifications have emerged, such as passive clearing (PACT) and methods to improve tissue staining. Here, we review advances and compare current applications with the aim of highlighting needed improvements as well as aiding selection of the specific protocol for use in future investigations.

neuroscience↗