Biology subjects

Ohl, F. W.

Publications and source records attributed to Ohl, F. W..

11 recordsLinked to original sources

bioRxiv2026

Performance-impacting brain state maladaptation driving disease progression in early mouse and human neuroinflammation

The neuronal mechanisms driving progression in neuroinflammatory disorders from early relapse-remitting phases to later neurodegenerative phases remain largely elusive. Functional brain state shifts towards hyperactivity, persisting beyond relapses, represent an early maladaptive response. Here, in remission stage of an experimental autoimmune encephalitis (EAE) mouse model of RRMS, we identified a reduced excitability upon optogenetic stimulation in the brain stem, the area of active disease, while in the cortex a persistent cortical neuronal hyperactivity and synaptic remodeling emerged, accompanied with an increase of markers of early apoptosis. In contrast, hippocampal circuits, which undergo a functional state shift without hyperactivity, do not show increased apoptosis. Visual cortical networks showed a deterioration of the accuracy of encoding visual information and a decrease in the behavioural visual discrimination ability in mice. In RRMS patients in remission, we identified a reduced visual colour discrimination, indicating both the presence and the clinical relevance of early brain state maladaptation that may contribute to progression independent from relapse activity (PIRA). SummaryIn a RRMS model and in patients, impaired visual processing was reported, indicating brain state maladaptations, associated with persistent cortical hyperactivity, brain stem hypoactivity, synaptic remodeling, and apoptosis. These maladaptations might contribute to relapse-independent disease progression through sustained network dysfunction.

neuroscience↗

bioRxiv2024

Tonotopy is not preserved in a descending stage of auditory cortex

Previous studies based on layer specificity suggest that ascending signals from the thalamus to the sensory neocortex preserve spatially organized information, but it remains unknown whether sensory information descending from sensory neocortex to the thalamus also maintains such spatial organization pattern. By focusing on projection specificity, we mapped the tone response properties of two groups of cortical neurons in the primary auditory cortex (A1), based on the relationship between their specific connections to other regions and their function in ascending (thalamocortical recipient, TR neurons) or descending (corticothalamic, CT neurons) auditory information. A clear tonotopic gradient was observed among TR neurons, but not CT neurons. Additionally, CT neurons exhibited markedly higher heterogeneity in their frequency tuning and had broader bandwidth than TR neurons. These results reveal that the information flow descending from A1 to the thalamus via CT neurons is not arrange tonotopically, suggesting that the descending information flow possibly contributes to higher-order feedback processing of diverse auditory inputs.

neuroscience↗

bioRxiv2022

Overcoming the Reproducibility Crisis - Results of the first Community Survey of the German National Research Data Infrastructure for Neuroscience.

The lack of reproducibility of research results is a serious problem - known as "the reproducibility crisis". The German National Research Data Infrastructure (NFDI) initiative implemented by the German Research Foundation (DFG) aims to help overcoming this crisis by developing sustainable solutions for research data management (RDM). NFDI comprises domain specific consortia across all science disciplines. In the field of neuroscience, NFDI Neuroscience (NFDI-Neuro) contributes to the strengthening of systematic and standardized RDM in its research communities. NFDI-Neuro conducted a comprehensive survey amongst the neuroscience community to determine the current needs, challenges, and opinions with respect to RDM. The outcomes of this survey are presented here. The German neuroscience community perceives barriers with respect to RDM and data sharing mainly linked to (1) lack of data and metadata standards, (2) lack of community adopted provenance tracking methods, 3) lack of a privacy preserving research infrastructure for sensitive data (4) lack of RDM literacy and (5) lack of required time and resources for proper RDM. NFDI-Neuro aims to systematically address these barriers by leading and contributing to the development of standards, tools, and infrastructure and by providing training, education, and support, as well as additional resources for RDM to its research community. The RDM work of NFDI-Neuro is conducted in close collaboration with its partner EBRAINS AISBL, the coordinating entity of the EU Flagship Human Brain Project, and its Research Infrastructure (RI) EBRAINS with more than 5000 registered users and developers from more than 70 countries of all continents. While NFDI-Neuro aims to address the German national needs, it closely aligns with the international community and the topics of the Digital Europe Program and EU Data Spaces. Significance StatementA comprehensive survey amongst the neuroscience community in Germany determined the current needs, challenges, and opinions with respect to standardized research data management (RDM) to overcome the reproducibility crisis. Significant deficits were pointed out concerning the perceived lack of standards for data and metadata, lack of provenance tracking and versioning of data, lack of protected digital research infrastructure for sensitive data and the lack of education and resources for proper RDM. Yet, at the same time, an overwhelming majority of community members indicated that they would be willing to share their data with other researchers and are interested to increase their RDM skills. Thus, the survey results suggest that training, the provision of standards, tools, infrastructure and additional resources for RDM holds the potential to significantly facilitate reproducible research in neuroscience.

neuroscience↗

bioRxiv2022

Inhibiting presynaptic calcium channel mobility in the auditory cortex suppresses synchronized input processing

The emergent coherent population activity from thousands of stochastic neurons in the brain is believed to constitute a key neuronal mechanism for salient processing of external stimuli and its link to internal states like attention and perception. In the sensory cortex, functional cell assemblies are formed by recurrent excitation and inhibitory influences. The stochastic dynamics of each cell involved is largely orchestrated by presynaptic CAV2.1 voltage-gated calcium channels (VGCCs). Cav2.1 VGCCs initiate the release of neurotransmitters from the presynaptic compartment and are therefore able to add variability into synaptic transmission which can be partly explained by their mobile organization around docked vesicles. To investigate the relevance of Cav2.1 channel surface mobility for the input processing in the primary auditory cortex (A1) in vivo, we make use of a new optogenetic system which allows us to acutely cross-link Cav2.1 VGCCs via a photo-cross-linkable cryptochrome mutant, CRY2olig. In order to map neuronal activity across all cortical layers of the A1, we performed laminar current-source density (CSD) recordings with varying auditory stimulus sets in transgenic mice with a citrine tag on the N-terminus of the VGCCs. Clustering VGCCs suppresses overall sensory-evoked population activity, particularly when stimuli lead to a highly synchronized distribution of synaptic inputs. Our findings reveal the importance of membrane dynamics of presynaptic calcium channels for sensory encoding by dynamically adjusting network activity across a wide range of synaptic input strength. Statement of SignificanceVoltage Gated Calcium Channel (VGCC) mobility plays an important role in neuronal firing dynamics. Failure of these channels to function or be regulated has been linked to migraine and ataxia. We here link the microscopic process of VGCC mobility to the mesoscopic population dynamics as a mechanism to regulate and appropriately amplify synaptic inputs of different strengths to the mouse primary auditory cortex. We also demonstrate a novel and effective technique with which VGCC function can be further explored in meso- or macroscopic scales and with behaving subjects. We believe that this is of importance to the broader scientific community in aspects of non-linear scaling in the brain, potential translational applications, and basic research on cortical mechanisms of physiological function.

neuroscience↗

bioRxiv2021

Thalamocortical and intracortical contributions to stimulus-evoked and oscillatory activity in rodent primary auditory cortex

Intracortical, horizontal connections seem ideally suited to contribute to cortical processing by spreading information across cortical space and coordinating activity between distant cortical sites. In sensory systems experiments have implicated horizontal connections in the generation of receptive fields and have in turn led to computational models of receptive field generation that rely on the contribution of horizontal connections. Testing the contribution of horizontal connections at the mesoscopic level has been difficult due to the lack of a suitable method to observe the activity of intracortical horizontal connections. Here, we develop such a method based on the analysis of the relative residues of the cortical laminar current source density reconstructions. In the auditory cortex of Mongolian gerbils, the method is then tested by manipulating the contribution of horizontal connections by surgical dissection. Our results indicate that intracortical horizontal connections contribute to the frequency-tuning of mesoscopic cortical patches. Futhermore, we dissociated a type of cortical gamma oscillation based on horizontal connections between mesoscopic patches from gamma oscillations locally generated within mesoscopic patches. The data further imply that global and local coordination of activity during sensory stimulation occur in a low and high gamma frequency band, respectively. Taken together the present data demonstrate that intracortical horizontal connections play an important role in generating cortical feature tuning and coordinate neuronal oscillations across cortex.

neuroscience↗

bioRxiv2020

TetrODrive: An open-source microdrive for combined electrophysiology and optophysiology

ObjectiveIn tetrode recordings, the cell types of the recorded units are difficult to determine based on electrophysiological characteristics alone. Optotagging, the use of optogenetic stimulation at the tip of electrodes to elicit spikes from genetically identified cells, is a method to overcome this challenge. However, recording from many different cells requires advancing electrodes and light sources slowly through the brain with a microdrive. Existing designs suffer from a number of drawbacks, such as limited stability and precision, high cost, complex assembly, or excessive size and weight. ApproachWe designed TetrODrive as a microdrive that can be 3D printed on an inexpensive desktop resin printer and has minimal parts, assembly time, and cost. The microdrive can be assembled in 15 minutes and the price for all materials, including the 3D printer, is lower than a single commercial microdrive. To maximize recording stability, we mechanically decoupled the drive mechanism from the electrical and optical connectors. Main resultsThe developed microdrive is small and light enough to be carried effortlessly by a mouse. It provides high signal-to-noise ratio recordings from optotagged units, even across recording sessions. Owing to its moveable optical fiber, our microdrive can also be used for fiber photometry. We evaluated our microdrive by recording single units and calcium signals in the ventral tegmental area (VTA) of mice and confirmed cell identity via optotagging. Thereby we found units not following the classical reward prediction error model. SignificanceTetrODrive is a tiny, lightweight, and affordable microdrive for optophysiology in mice. Its open design, price, and built-in characteristics can significantly expand the use of microdrives in mice.

neuroscience↗

bioRxiv2020

Acute and long-term circuit-level effects in the auditory cortex after sound trauma

Harmful environmental sounds are a prevailing source for chronic hearing impairments, including noise induced hearing loss, hyperacusis, or tinnitus. How these symptoms are related to pathophysiological damage to the sensory receptor epithelia and its effects along the auditory pathway, such as functional reorganizations in the auditory cortex (ACx), have been documented in numerous studies. An open question concerns the temporal evolution of maladaptive changes after damage and their manifestation in the balance between afferent thalamocortical input and corticocortical input to the ACx. To address this, we investigated the loci of plastic reorganizations across the tonotopic axis of the auditory cortex of male Mongolian gerbils (Meriones unguiculatus) acutely after a sound trauma and after several weeks. We used a laminar residual current-source density analysis to dissociate adaptations of intracolumnar input and horizontally relayed corticocortical input to synaptic populations across cortical layers in ACx. A pure tone-based sound trauma caused acute changes of subcortical inputs and corticocortical inputs at all tonotopic regions, particularly showing a broad elimination of tone-evoked inputs at tonotopic regions with a pre-trauma best frequency between 2-8 kHz. At other cortical sites, the overall columnar activity acutely decreased, while relative contributions of lateral corticocortical inputs increased. After 4-6 weeks, cortical activity to the altered sensory inputs showed a general increase of local thalamocortical input reaching levels higher than before the trauma. Hence, our results suggest a detailed mechanism for overcompensation of altered frequency input in the auditory cortex that relies on a changing balancing of thalamocortical and intracortical input and is confined to the spectral neighborhood of the trauma frequency. Significance statementHarmful noise exposure is a major anthropogenic cause of hearing disorders and is becoming an ever-increasing burden for human health and society. Damage to the sensory epithelia elicited by harmful sounds can subsequently lead to chronic hearing loss, hyperacusis or tinnitus. We still lack an understanding of the pathophysiological plastic processes and their evolution, particularly at the circuit level of the auditory cortex (ACx), which is fundamentally involved in auditory perception. We demonstrate that plastic changes in ACx after noise induced hearing loss (NIHL) occur over several weeks, and that changes in intracortical functional connectivity compensate the acute effects in the deafferentiated subcortical inputs. Such long-term changes may underlie the temporal evolution of hearing impairments or phantom sounds after NIHL.

neuroscience↗

bioRxiv2019

Task rule and choice are reflected by layer-specific processing in rodent auditory cortical microcircuits

The primary auditory cortex (A1) is an essential node in the integrative brain network that encodes the behavioral relevance of acoustic stimuli, predictions, and auditory-guided decision making. Previous studies have revealed task-related information being present at both the single-unit and population activity. However, its realization with respect to the cortical microcircuitry is less well understood. In this study, we used chronic, laminar current source density (CSD) analysis from the A1 of behaving Mongolian gerbils (Meriones unguiculatus) in order to characterize layer-specific, spatiotemporal synaptic population activity. Animals were trained to first detect and subsequently to discriminate two pure tone frequencies in consecutive training phases in a Go/NoGo shuttle-box task. We demonstrate that not only sensory but also task- and choice-related information is represented in the mesoscopic neuronal population code distributed across cortical layers. Based on a single-trial analysis using generalized linear-mixed effect models (GLMM), we found infragranular layers to be involved in auditory-guided action initiation during tone detection. Supragranular layers, particularly, are involved in the coding of choice options during tone discrimination. Further, we found that the overall columnar synaptic network activity represents the accuracy of the opted choice. Our study thereby suggests a multiplexed representation of stimulus features in dependence of the task, action selection, and the behavioral options of the animal in preparation of correct choices. The findings expand our understanding of how individual layers contribute to the integrative circuit of the A1 in order to code task-relevant information and guide sensory-based decision making.

neuroscience↗

bioRxiv2019

Ketamine anesthesia induces gain enhancement via recurrent excitation in granular input layers of the auditory cortex

The N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine, is commonly used as an anesthetic agent and has more recently gained attention as an antidepressant. Ketamine has been linked to increased stimulus-locked excitability, inhibition of interneurons, and modulation of intrinsic neuronal oscillations. However, the functional network mechanisms are still elusive. A better understanding of these anesthetic network effects may improve upon previous interpretations of seminal studies conducted under anesthesia and have widespread relevance for neuroscience with awake and anesthetized subjects as well as in medicine. Here, we investigated the effects of anesthetic doses of ketamine (15mg kg-1/h i.p.) on the network activity after pure tone stimulation within the auditory cortex of male Mongolian gerbils (Meriones unguiculatus). We used laminar current source density (CSD) analysis and subsequent layer-specific continuous wavelet analysis to investigate spatiotemporal response dynamics on cortical columnar processing in awake and ketamine-anesthetized animals. We found thalamocortical input processing within granular layers III/IV to be significantly increased under ketamine. This effect on early thalamocortical input processing was not due to changes in cross-trial phase coherence. Rather, the layer-dependent gain enhancement under ketamine was attributed to a broadband increase in amplitude reflecting an increase in recurrent excitation. The time-frequency analysis is further indicative of a prolonged period of stimulus-induced excitation possibly due to a reduced coupling of excitation and inhibition in granular input circuits--in line with the common hypothesis of cortical disinhibition via NMDA-mediated suppression of GABAergic interneurons.\n\nStatement of significanceKetamine is a common anesthetic agent and is known to alter excitability and neuronal synchronicity in the cortex. We reveal here that anesthetic doses of ketamine increase recurrent excitation of thalamic input in the granular layers of the auditory cortex of Mongolian gerbils. This leads to a layer-specific gain enhancement of the time-locked response to external stimuli. Analysis of tone-evoked amplitudes and cross-trial variability of cortical current sources and sinks indicate a mechanism of cortical disinhibition via NMDA-mediated suppression of GABAergic interneurons. Our findings might help to understand the functional mechanisms of the clinical effects of ketamine promoting the development of new therapeutic agents with lower side effects.

neuroscience↗

bioRxiv2019

Electrochemical Roughening and Carbon Nanotube Coating of Tetrodes for Chronic Single-Unit Recording

Recording from single neurons in the brain for long periods of time has been a central goal in both basic neuroscience and translational neurology, in order to understand mechanisms underlying brain processes such as learning and to understand the pathogenesis of neurodynamic disease states 1. Recent advances in materials engineering, digital signal acquisition, and analysis algorithms have brought us closer to achieving this goal, and the possibility has gathered much public attention 2,3. However, it remains a challenge to record from the same units for weeks to months. Here, we record many high-quality tetrode neuronal signals reliably over long periods of time in both deep and superficial areas of the brain. We achieve this by combining electrochemical roughening and carbon nanotube coating of a flexible platinum/iridium substrate, with materials, packaging, and insertion optimized to minimize tip movement with brain pulsation. This \"Magdeburger\" probe enables recordings with long-term signal stability and high signal-to-noise ratio at a reasonable cost in both rodent brains and in substantially larger primate brains. Robust tetrode tracking of identified neurons over longer time periods, in multiple independently targeted areas of the brain, will allow fundamental advances in the study of cognitive learning, aging, and pathogenesis, and opens new possibilities for brain interfaces in humans.

bioengineering↗

bioRxiv2019

The VTA modulates a frequency-specific gain of thalamocortical inputs in infragranular layers of the gerbil auditory cortex

BackgroundReward associations during auditory learning induce cortical plasticity in the primary auditory cortex. A prominent source of such influence is the ventral tegmental area (VTA), which conveys a dopaminergic teaching signal to the primary auditory cortex. It is currently unknown, however, how the VTA circuitry thereby influences cortical frequency information processing and spectral integration. In this study, we therefore investigated the temporal effects of direct optogenetic stimulation of the VTA onto spectral integration in the auditory cortex on a synaptic circuit level by current-source-density analysis in anesthetized Mongolian gerbils.\n\nResultsWhile auditory lemniscal input predominantly terminates in the granular input layers III/IV, we found that VTA-mediated modulation of spectral processing is relayed by a different circuit, namely enhanced thalamic inputs to the infragranular layers Vb/VIa. Activation of this circuit yields a frequency-specific gain amplification of local sensory input and enhances corticocortical information transfer, especially in supragranular layers I/II. This effects further persisted over more than 30 minutes after VTA stimulation.\n\nConclusionsAltogether, we demonstrate that the VTA exhibits a long-lasting influence on sensory cortical processing via infragranular layers transcending the signaling of a mere reward-prediction error. Our findings thereby demonstrate a cellular and circuit substrate for the influence of reinforcement-evaluating brain systems on sensory processing in the auditory cortex.

neuroscience↗