Biology subjects

Strasburger, H.

Publications and source records attributed to Strasburger, H..

4 recordsLinked to original sources

bioRxiv2023

A comparative analysis of microglial inducible Cre lines

Cre/LoxP technology has revolutionized genetic studies and allowed for spatial and temporal control of gene expression in specific cell types. The field of microglial biology has particularly benefited from this technology as microglia have historically been difficult to transduce with virus or electroporation methods for gene delivery. Here, we interrogate four of the most widely available microglial inducible Cre lines. We demonstrate varying degrees of recombination efficiency and spontaneous recombination, depending on the Cre line and loxP distance. We also establish best practice guidelines and protocols to measure recombination efficiency in microglia, which could be extended to other cell types. There is increasing evidence that microglia are key regulators of neural circuit structure and function. Microglia are also major drivers of a broad range of neurological diseases. Thus, reliable manipulation of their function in vivo is of utmost importance. Identifying caveats and benefits of all tools and implementing the most rigorous protocols are crucial to the growth of the field of microglial biology and the development of microglia-based therapeutics.

neuroscience↗

bioRxiv2021

Spectral dependency of the human pupillary light reflex. Influences of pre-adaptation and chronotype.

Non-visual photoreceptors (ipRGCs) and rods both exert a strong influence on the human pupil, yet pupil models regularly use cone-derived sensitivity as their basis. This inconsistency is further exacerbated by the fact that circadian effects can modulate the wavelength sensitivity. We assessed the pupillary reaction to monochromatic light stimuli in the mesopic range. Pupil size for eighty-three healthy participants with normal color vision was measured in nine experimental protocols with varying series of continuous or discontinuous light stimuli under Ganzfeld conditions, presented after 90 seconds of dark adaptation. One hundred and fifty series of stimulation were conducted across three experiments, and were analyzed for wavelength-dependency on the pupillary constriction amplitude (PCA), conditional on experimental settings and individual traits. Traits were surveyed by questionnaire; color vision was tested by Ishihara plates or the Lanthony D15 test. Data were analyzed with generalized additive mixed models (GAMM). The pupillary constriction amplitude response is consistent with L+M-cone derived sensitivity when the series of light stimuli is continuous, i.e., is not interrupted by periods of darkness, but not otherwise. The results also show that a mesopic illuminance weighing led to an overall best prediction of pupillary constriction compared to other types of illuminance measures. IpRGC influence on PCA is not readily apparent from the results. When we explored the interaction of chronotype and time of day on the wavelength dependency, differences consistent with ipRGC influence became apparent. The models indicate that subjects of differing chronotype show a heightened or lowered sensitivity to short wavelengths, depending on their time of preference. IpRGC influence is also seen in the post-illumination pupil reflex if the prior light-stimulus duration is one second. However, shorter wavelengths than expected become more important if the light-stimulus duration is fifteen or thirty seconds. The influence of sex on PCA was present, but showed no interaction with wavelength. Our results help to define the conditions, under which the different wavelength sensitivities in literature hold up for monochromatic light settings. The chronotype effect might signify a mechanism for strengthening the individuals chronotype, but demands replication in a controlled study.

physiology↗

bioRxiv2019

On the cortical mapping function -- visual space, cortical space, and crowding

The retino-cortical visual pathway is retinotopically organized: Neighbourhood relationships on the retina are preserved in the mapping to the cortex. Size relationships in that mapping are also highly regular: The size of a patch in the visual field that maps onto a cortical patch of fixed size follows, along any radius and in a wide range, simply a linear function with retinal eccentricity. As a consequence, and under simplifying assumptions, the mapping of retinal to cortical locations follows a logarithmic function along that radius. While this has already been shown by Fischer (1973), the link between the linear function - which describes the local behaviour by the cortical magnification factor M - and the logarithmic location function for the global behaviour, has never been made fully explicit. The present paper provides such a link as a set of ready-to-use equations using Levi and Kleins E2 nomenclature, and examples for their validity and applicability in the retinotopic mapping literature are discussed. The equations allow estimating M in the retinotopic centre and values thus derived from the literature are provided. A new structural parameter, d2, is proposed to characterize the cortical map, as a cortical counterpart to E2, and typical values for it are given. One pitfall is discussed and spelt out as a set of equations, namely the common myth that a pure logarithmic function will give an adequate map: The popular omission of a constant term renders the equations ill defined in, and around, the retinotopic centre. The correct equations are finally extended to describe the cortical map of Boumas law on visual crowding. The result contradicts recent suggestions that critical crowding distance corresponds to a constant cortical distance.

neuroscience↗

bioRxiv2018

Oligodendrocyte Precursor Cells Are Co-Opted by the Immune System to Cross-Present Antigen and Mediate Cytotoxicity

Oligodendrocyte precursor cells (OPCs) are abundant in the adult CNS and can be recruited to form new oligodendrocytes and myelin in response to injury or disease. However, in multiple sclerosis (MS), oligodendrocyte regeneration and remyelination are often incomplete, suggesting that recruitment and maturation of OPCs is impaired. MS and the rodent model experimental autoimmune encephalomyelitis (EAE) are characterized by infiltration of activated T-cells into the CNS. To investigate the mechanisms by which this neuroinflammatory process influences OPC mobilization, we performed in vivo fate tracing in an inflammatory demyelinating animal model. Results of our studies showed that the OPC differentiation and myelin production are inhibited by either adoptive transfer of CNS infiltrating cytokine producing effector T-cells or CNS production of interferon gamma (IFN{gamma}), using an astrocyte specific IFN{gamma} transgene model. In both systems, IFN{gamma} changes the profile of OPCs by inducing functional expression of the immunoproteasome and upregulation of MHC class I. OPCs exposed to IFN{gamma} are shown to cross present exogenous antigen to cytotoxic CD8 T-cells, which then produce proteases and FasL that results in subsequent caspase 3/7 activation and OPC death, both in vitro and in vivo. Cross presentation by OPCs is dependent on the cytosolic processing pathway and can be inhibited by small molecules targeting MHC class I antigen processing and the immunoproteasome subunits. Finally, the immunoproteasome subunit, PSMB8, is shown to be markedly increased on Sox10+ oligodendrocyte lineage cells only in the demyelinated white matter lesions from patients with MS. These findings support the notion that OPCs have multiple functions beyond differentiation into myelinating cells and adapt to their microenvironment by responding to local cues. In MS, OPCs may be co-opted by the immune system to perpetuate the autoimmune response. Strategies aimed at inhibiting the aberrant immune activation pathways in OPCs may allow more efficient remyelination in MS.

neuroscience↗