Biology subjects

Siebner, H.

Publications and source records attributed to Siebner, H..

12 recordsLinked to original sources

bioRxiv2026

Cortical pyramidal tract neurons constrain pathological dopaminergic motor responses

Pyramidal tract (PT) neurons constitute a major cortical output pathway to subcortical structures, yet their contribution to parkinsonian and dyskinetic motor states remains unclear. Here, we show that chemogenetic activation of motor cortical PT neurons selectively confines pathological dopaminergic motor responses. Unilateral PT chemogenetic activation suppressed spontaneous locomotion in healthy mice but did not improve motor deficits following an ipsilateral 6-hydroxydopamine lesion. Instead, it attenuated contraversive rotations provoked by pharmacological D1-receptor stimulation and selectively reduced axial levodopa-induced dyskinesia. Mechanistically, PT stimulation reduced acute D1-mediated c-Fos induction in the dopamine-depleted striatum, without affecting chronic {Delta}FosB accumulation induced by repeated levodopa exposure. These findings identify a functional interaction between cortical PT output and striatal D1-receptor signalling that limits maladaptive motor responses to dopaminergic stimulation. Our results uncover a previously unrecognised cortical mechanism regulating pathological motor behaviour and suggest PT neurons as a potential substrate for circuit-based therapies in Parkinson's disease.

neuroscience↗

bioRxiv2026

Lifestyle modulates riverbed diazotrophy: from abundance and activity to diversity of free-living and biofilm-associated N2 fixers

Despite the critical role that biological N2 fixation plays in controlling primary and secondary production in aquatic ecosystems, freshwater subsurface diazotrophy has received minimal attention. Here, we quantified N2 fixation rates, diazotroph abundance, and diversity in the hyporheic zone across seasons and redox regimes, distinguishing between free-living and biofilm-associated lifestyles. Samples were collected from aerobic and suboxic strata of the Jordan River streambed and incubated in microcosms for 24 h with dissolved 15N2 under ambient conditions. Immunolabeling the nitrogenase enzyme coupled with flow-cytometry revealed that diazotrophs accounted for [≤]9.6 % of total bacterial abundance but were consistently enriched in biofilms. These biofilms supported 377-fold higher N2 fixation rates per-cell than free-living diazotrophs. Confocal laser scanning microscopy captured thicker (several tens of microns) complexes of extracellular polymeric substances (EPS) encasing aerobic biofilms than suboxic, especially during winter. Biofilm-associated communities retained high abundances ([≤]21 %) of facultative and obligate anaerobes in oxic zones. Compared to those in biofilms, the abundance, N2 fixation rates, and diversity of the free-living fraction varied much more across both aerobic and suboxic zones. nifH sequencing unveiled the dominance of Pseudomonadota and Thermodesulfobacteriota across all communities. Overall N2 fixing activity, when converted to volumetric units, was 1.5 x 105-fold greater in the streambed than the overlying water. These findings identify the hyporheic zone as an active hotspot for benthic diazotrophy and intimate the centrality of microbial lifestyle in determining how diazotrophs persist and remain highly active in fluctuating redox and nutrient conditions in the freshwater ecospace.

microbiology↗

bioRxiv2026

Dryland soil rewetting induces strong VOC emissions with potential to form ozone and aerosols

Biogenic volatile organic compounds (VOCs) significantly influence atmospheric chemistry, yet the importance of microbial VOC emissions remains understudied. We investigate petrichor VOC emissions, the characteristic scent following rainfall after prolonged drought, in an aridity gradient across Israel, by simulating soil rewetting events. Rewetting triggered strong VOC fluxes (1-3.5 nmol m-2 s-1 ground area) dominated by sesquiterpenes and benzenoids, with emission patterns linked to climatic regions, soil aridity, and microbial community composition. Petrichor consisted of a complex bouquet of 58 VOCs, and the initial VOC burst resembled the CO2 pulse of the Birch effect. Petrichor emissions showed ozone and secondary organic aerosol formation potentials comparable in magnitude to those estimated for anthropogenic VOC sources in Israel. Despite compositional differences, emissions were of similar magnitudes across the aridity gradient. Given that drylands cover nearly half of Earths terrestrial surface and are expanding, these episodic microbial VOC emissions may represent a significant, previously overlooked source of reactive carbon with potential implications for regional and global atmospheric chemistry.

microbiology↗

bioRxiv2026

No group-level changes in corticospinal excitability following low-intensity theta-burst ultrasound stimulation of the primary motor hand area.

BackgroundLow-intensity transcranial ultrasound stimulation (TUS) is a novel non-invasive brain-stimulation technique offering high spatial precision and depth penetrance. Theta burst TUS (tbTUS), featuring a temporal theta burst stimulation pattern, has been reported to facilitate corticomotor excitability, when applied to the human primary motor hand area (M1-HAND). However, replication attempts have yielded inconsistent results. MethodsFifteen healthy human participants underwent neuronavigated tbTUS targeting the left M1-HAND in the anterior wall of the precentral sulcus, as well as anterior and posterior active control sites. The three tbTUS conditions were applied in counterbalanced order on separate days. Corticospinal excitability was assessed via motor evoked potentials (MEPs) recorded before and 5, 15, 30, and 60 minutes after tbTUS, and analyzed using an rmANOVA. ResultsNone of the tbTUS conditions produced consistent group-level changes in MEP amplitude at any time point. Both intra- and inter-subject variability were high, and individual MEP changes following precentral tbTUS did not correlate with changes after control-site stimulation. ConclusionsWe did not observe reliable modulatory effects of neuronavigated tbTUS on corticospinal excitability. Methodological and hardware differences may account for discrepancies across studies. Our findings align with recent reports questioning the robustness of tbTUS-induced facilitation.

neuroscience↗

bioRxiv2025

Not two sides of the same coin: Divergent effects of motor state on corticospinal and cortical responses to TMS of motor cortex

BackgroundTranscranial magnetic stimulation (TMS) of the motor cortex can elicit motor evoked potentials (MEPs) in target muscles, reflecting corticospinal excitability. MEP amplitudes increase with TMS intensity and can be facilitated by tonic muscle pre-activation. Since conventional transcranial evoked potentials (TEPs) also grow with increasing TMS intensity, cortical and corticospinal responses are often considered two facets of the same process. If this were true, changes in physiological motor state should modulate TEPs and MEPs in a similar manner. MethodsTo compare the state-dependency of cortical and corticospinal responses to single-pulse TMS, we simultaneously recorded TEPs and MEPs in 16 healthy young adults during relaxation and isometric contraction of the right first dorsal interosseous (FDI) muscle. For each condition, 100 biphasic TMS pulses were delivered to the left primary motor hand area at five different intensities centered around the resting motor threshold. ResultsTEP and MEP amplitudes increased with stimulation intensity. As predicted, tonic muscle contraction consistently facilitated MEP. On the contrary, muscle contraction attenuated two key peaks of the TEP (N15 and N100). The state-dependent effects of corticospinal and cortical responses were not correlated. DiscussionBoth TEPs and MEPs are reliably modulated by motor state, yet they differ in direction and their magnitudes do not scale with each other. These findings challenge the assumption that cortical and corticospinal responses are two aspects of the same process. MEP facilitation during contraction likely reflects increased spinal excitability, whereas TEP attenuation may reflect reduced responsiveness of cortico-cortical or cortico-subcortical networks.

neuroscience↗

bioRxiv2024

Heterotrophic diazotrophy along a river to lake continuum: lifestyle and contribution to N2 fixation

Heterotrophic diazotrophs are potentially important agents in freshwater ecosystems, yet they remain poorly understood. This study elucidates the contribution of freshwater heterotrophic diazotrophs as free-living or aggregate-associated cells to total N2 fixation along the continuum from the Jordan River to Lake Kinneret, Israel. Heterotrophic diazotrophs accounted for 25%-56% of the total diazotrophs and commonly found as free-living cells or attached to aggregates in the river. N2 fixation by heterotrophic diazotrophs associated with aggregates varied along the river, while accounting for ~50% of N2 fixation in the lake. Non-cyanobacterial diazotrophs dominated the free-living fraction in the river, and cyanobacteria were mostly identified in the lake. The diversity of free-living diazotrophs was sensitive to environmental changes, as the aggregates have likely provided a protected micro-environment. The results reveal the dynamic lifestyle of heterotrophic diazotrophs along a river-lake continuum and highlight their contribution to total N2 fixation and primary production. TeaserFreshwater heterotrophic diazotrophs are more ubiquitous than previously thought, can be found as free-living cells or associated with aggregates, and significantly contribute to primary production.

microbiology↗

bioRxiv2024

Head And Shoulders - The Impact Of An Extended Head Model On The Simulation And Optimization Of Transcranial Electric Stimulation

Electric field calculations are increasingly used for dose characterization of transcranial electrical stimulation (tES), but existing open-source head models are inaccurate for extracephalic montages that include electrodes placed on the neck or shoulder. We introduce the "Ernie Extended" model, an MRI- and CT-derived open-source head model extending to the upper shoulder region. Simulations of extracephalic tES targeting the cerebellum and supplementary motor area show significant differences in electric fields when using Ernie Extended compared to the non-extended Ernie model. Additionally, we propose an electrode layout that complements the electroencephalography 10- 20 system with extracephalic electrode positions. We demonstrate the use of this layout for optimizing multi-electrode tES montages for cerebellar stimulation, enhancing focality and reducing off-target stimulation, particularly of the spinal cord. Our results highlight the practical value of the Ernie Extended model for accurately characterizing doses produced by extracephalic tES montages and when targeting more caudal brain regions.

neuroscience↗

bioRxiv2022

Quantification of Aquatic Unicellular Diazotrophs by Immunolabeled Flow Cytometry

Quantifying the number of aquatic diazotrophs is highly challenging and relies mainly on microscopical approaches and/or molecular tools that are based on nif genes. However, it is still challenging to count diazotrophs, especially the unicellular fraction, despite their significant contribution to the aquatic nitrogen cycle. In this study a new method was developed to quantify unicellular diazotrophs by immunolabeling the nitrogenase enzyme followed by identification and quantification via flow cytometry. The new quantification method was initially developed using a diazotrophic monoculture (Vibrio natriegens) and verified by various auxiliary approaches. It was found that only 15-20% of the total number of V. natriegens cells have synthesized the nitrogenase enzyme, even though the media was anaerobic, and N limited. This approach was further tested in samples from marine and freshwater environments. It was found that the ratio of diazotrophs to total bacteria was 0.1% in the Mediterranean Sea, while 4.7% along the Jordan River. In contrast, the specific N2 fixation per unicellular diazotrophs was highest in the Mediterranean Sea (88 attomole N cell-1 d-1) while the total N2 fixation rates were lowest in the lake and the river (0.2 nmole N L-1 d-1). Overall, we expect that this direct quantification approach will provide new insights on the number and contribution of unicellular diazotrophs to total N2 fixation in marine and freshwater environments under various conditions.

microbiology↗

bioRxiv2021

The response of desert biocrust bacterial communities to hydration-desiccation cycles

Rain events in arid environments are highly unpredictable, interspersing extended periods of drought. Therefore, following changes in desert soil bacterial communities during hydration-desiccation cycles in the field, was seldom attempted. Here, we assessed rain-mediated dynamics of active community in the Negev Desert biological soil crust (biocrust), and evaluated the changes in bacterial composition, potential function, and photosynthetic activity. We predicted that increased biocrust moisture would resuscitate the phototrophs, while desiccation would inhibit their activity. Our results show that hydration increased chlorophyll content, resuscitated the biocrust Cyanobacteria, and induced potential phototrophic functions. However, decrease in the soil water content did not immediately decrease the phototrophs activity, though chlorophyll levels decreased. Moreover, while the Cyanobacteria relative abundance significantly increased, Actinobacteria, the former dominant taxa, significantly decreased in abundance. We propose that, following a rain event biocrust moisture significantly decreased, almost to drought levels, yet the response of the active bacterial community lagged, in contrast to topsoil. Possible explanations to the described rain-mediated bacteria dynamics are discussed.

microbiology↗

bioRxiv2020

Beneficial effects of cerebellar tDCS on motor learning are associated with altered putamen-cerebellar connectivity: a simultaneous tDCS-fMRI study

Non-invasive transcranial stimulation of cerebellum and primary motor cortex (M1) has been shown to enhance motor learning. However, the mechanisms by which stimulation improves learning remain largely unknown. Here, we sought to shed light on the neural correlates of transcranial direct current stimulation (tDCS) during motor learning by simultaneously recording functional magnetic resonance imaging (fMRI). We found that right cerebellar tDCS, but not left M1 tDCS, led to enhanced sequence learning in the serial reaction time task. Performance was also improved following cerebellar tDCS compared to sham in a sequence production task, reflecting superior training effects persisting into the post-training period. These behavioral effects were accompanied by increased learning-specific activity in right M1, left cerebellum lobule VI, left inferior frontal gyrus and right inferior parietal lobule during cerebellar tDCS compared to sham. Despite the lack of group-level changes comparing left M1 tDCS to sham, activity increase in right M1, supplementary motor area, and bilateral superior frontal cortex, under M1 tDCS, was associated with better sequence performance. This suggests that lack of group effects in M1 tDCS relate to inter-individual variability in learning-related activation patterns. We further investigated how tDCS modulates effective connectivity in the cortico-striato-cerebellar learning network. Using dynamic causal modelling, we found altered connectivity patterns during both M1 and cerebellar tDCS when compared to sham. Specifically, during cerebellar tDCS, negative modulation of a connection from putamen to cerebellum was decreased for sequence learning only, effectively leading to decreased inhibition of the cerebellum. These results show specific effects of cerebellar tDCS on functional activity and connectivity in the motor learning network and may facilitate the optimization of motor rehabilitation involving cerebellar non-invasive stimulation.

neuroscience↗

bioRxiv2019

Regional glia-related metabolite levels are higher at older age and scale negatively with visuo-spatial working memory: A cross-sectional proton MR spectroscopy study at 7 tesla on normal cognitive ageing

Proton MR spectroscopy (1H-MRS) has been used to assess regional neurochemical brain changes during normal ageing, but results have varied. Exploiting the increased sensitivity at ultra-high field strength, we performed 1H-MRS in 60 healthy volunteers to asses age-related differences in neuron- and glia-related metabolite levels and their relation to cognitive ageing. Gender was balanced and participants were assigned to a younger, middle and older group according to their age, ranging from 18 to 79 years. They underwent 1H-MRS of anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), hippocampus and thalamus and performed a visuo-spatial working memory task outside the scanner. Multivariate ANCOVA revealed a significant overall effect of age group on metabolite levels in all brain regions of interest. Considering specific metabolites, elevated levels of glia-related metabolites in older age groups were observed in all brain regions. For the neuron-related metabolites, differences among age groups were only observed in two regions. We found higher levels of total N-acetyl aspartate in hippocampus for the older than the middle group, and lower levels of glutamate in DLPFC in the older than the younger group. Working memory performance correlated negatively with levels of glia-related metabolites for total creatine and total choline in ACC and myo-inositol in hippocampus and thalamus, but not with neuron-related metabolites. Together, the results show that age effects on glia-related metabolites scale with cognitive ageing in multiple brain regions. We conclude that 1H-MRS-derived glia-related markers may be of value in longitudinal studies of brain ageing. Significance statementNeurochemical ageing is an integral component of age-related cognitive decline. Proton MR spectroscopy (1H-MRS) studies of in vivo neurochemical changes across the lifespan have, however, yielded inconclusive results. Due to the higher spectral resolution and sensitivity, 7 tesla 1H-MRS has potential to improve consistency of the results. Here we apply this technique to demonstrate that glia-related metabolites are elevated in older age in anterior cingulate cortex, hippocampus and thalamus with a novel link to cognitive ageing of visuo-spatial working memory. This study is the first to investigate normal ageing in these brain regions using 7 tesla 1H-MRS and the results indicate that glia-related metabolites could be of value in longitudinal studies of cognitive ageing.

neuroscience↗

bioRxiv2018

Reward signalling in brainstem nuclei under glycemic flux

Phasic dopamine release from mid-brain dopaminergic neurons signals errors of reward prediction (RPE). If reward maximisation is to maintain homeostasis, then the value of primary rewards should be coupled to the homeostatic errors they remediate. This leads to the prediction that RPE signals should be configured as a function of homeostatic state and thus, diminish with the attenuation of homeostatic error. To test this hypothesis, we collected a large volume of functional MRI data from five human volunteers on four separate days. After fasting for 12 hours, subjects consumed preloads that differed in glucose concentration. Participants then underwent a Pavlovian cue-conditioning paradigm in which the colour of a fixation-cross was stochastically associated with the delivery of water or glucose via a gustometer. This design afforded computation of RPE separately for better- and worse-than expected outcomes during ascending and descending trajectories of physiological serum glucose fluctuations. In the parabrachial nuclei, variations in regional activity coding positive RPEs scaled positively with serum glucose for ascending and descending glucose levels. The ventral tegmental area and substantia nigra became more sensitive to negative RPEs when glucose levels were ascending. Together, the results show that RPE signals in key brainstem structures are modulated by homeostatic trajectories of naturally occurring glycemic flux, revealing a tight interplay between homeostatic state and the neural encoding of primary reward in the human brain.

neuroscience↗