New Publication: ATP activation of peritubular cells drives testicular sperm transport

Januar 29, 2021

David Fleck, Lina Kenzler, Nadine Mundt, Martin Strauch, Naofumi Uesaka, Robert Moosmann, Felicitas Bruentgens, Annika Missel, Artur Mayerhofer, Dorit Merhof, Jennifer Spehr, Marc Spehr (2021) ATP activation of peritubular cells drives testicular sperm transport. eLife 2021;10:e62885.
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Spermatogenesis, the complex process of male germ cell proliferation, differentiation, and maturation, is the basis of male fertility. In the seminiferous tubules of the testes, spermatozoa are constantly generated from spermatogonial stem cells through a stereotyped sequence of mitotic and meiotic divisions. The basic physiological principles, however, that control both maturation and luminal transport of the still immotile spermatozoa within the seminiferous tubules remain poorly, if at all, defined. Here, we show that coordinated contractions of smooth muscle-like testicular peritubular cells provide the propulsive force for luminal sperm transport toward the rete testis. Using a mouse model for in vivo imaging, we describe and quantify spontaneous tubular contractions and show a causal relationship between peritubular Ca2+ waves and peristaltic transport. Moreover, we identify P2 receptor-dependent purinergic signaling pathways as physiological triggers of tubular contractions both in vitro and in vivo. When challenged with extracellular ATP, transport of luminal content inside the seminiferous tubules displays stage-dependent directionality. We thus suggest that paracrine purinergic signaling coordinates peristaltic recurrent contractions of the mouse seminiferous tubules to propel immotile spermatozoa to the rete testis.

New Publication: Influence of Size and Cross-Linking Density of Microgels on Cellular Uptake and Uptake Kinetics

Mai 27, 2020

Victoria K Switacz, Sarah K. Wypysek, Rudolf Degen, Jérôme J. Crassous, Marc Spehr and Walter Richtering (2020) Influence of Size and Cross-Linking Density of Microgels on Cellular Uptake and Uptake Kinetics. Biomacromolecules.

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The unique pH and temperature responsiveness of PNIPAM-based microgels make them a promising target for novel biomedical applications such as cellular drug delivery systems. However, we lack a comprehensive understanding of how the physicochemical properties of microgels relate to their interaction with cells. Here, we show that HEK293T cells take up PNIPAM-based microgels on a second-to-minute time scale. Uptake rates are determined by microgel size and cross-linker content. Using fluorescence confocal live-cell microscopy, we observe microgel uptake in real time and describe cellular uptake kinetics. Experiments reveal that small and less cross-linked microgels show faster uptake kinetics than microgels of larger size or higher cross-linker content. Only microgels that are larger than 800 nm in diameter and have cross-linking contents of 10–15 mol % do not show translocation into cells. Together, these results provide insight into microgel–cell interactions and generate quantitative information on the deterministic role of microgel architecture—i.e., size and rigidity—for uptake by a prototypical human cell line.

New Publication: Synchronous Infra-Slow Oscillations Organize Ensembles of Accessory Olfactory Bulb Projection Neurons into Distinct Microcircuits

Mai 20, 2020

Chryssanthi Tsitoura, Sebastian T. Malinowski, Julia Mohrhardt, Rudolf Degen, Brett T. DiBenedictis, Yuan Gao, Katja Watznauer, Kira Gerhold, Maximilian Nagel, Monika Weber, Markus Rothermel, Ileana L. Hanganu-Opatz, Yoram Ben-Shaul, Ian G. Davison and Marc Spehr (2020) Synchronous Infra-Slow Oscillations Organize Ensembles of Accessory Olfactory Bulb Projection Neurons into Distinct Microcircuits. Journal of Neuroscience 40 (21).

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The accessory olfactory system controls social and sexual behavior. In the mouse accessory olfactory bulb, the first central stage of information processing along the accessory olfactory pathway, projection neurons (mitral cells) display infra-slow oscillatory discharge with remarkable periodicity. The physiological mechanisms that underlie this default output state, however, remain controversial. Moreover, whether such rhythmic infra-slow activity patterns exist in awake behaving mice and whether such activity reflects the functional organization of the accessory olfactory bulb circuitry remain unclear. Here, we hypothesize that mitral cell ensembles form synchronized microcircuits that subdivide the accessory olfactory bulb into segregated functional clusters. We use a miniature microscope to image the Ca2+ dynamics within the apical dendritic compartments of large mitral cell ensembles in vivo. We show that infra-slow periodic patterns of concerted neural activity, indeed, reflect the idle state of accessory olfactory bulb output in awake male and female mice. Ca2+ activity profiles are distinct and glomerulus-specific. Confocal time-lapse imaging in acute slices reveals that groups of mitral cells assemble into microcircuits that exhibit correlated Ca2+ signals. Moreover, electrophysiological profiling of synaptic connectivity indicates functional coupling between mitral cells. Our results suggest that both intrinsically rhythmogenic neurons and neurons entrained by fast synaptic drive are key elements in organizing the accessory olfactory bulb into functional microcircuits, each characterized by a distinct default pattern of infra-slow rhythmicity.

Nadine Mundt wurde als „Young Scientist“ ausgewählt und eingeladen, am 70. Lindau Nobel Laureate Meeting 2020 teilzunehmen! Herzlichen Glückwunsch, Nadine!

März 4, 2020
© Lindau Nobel Laureate Meetings

Nadine ist eine von 660 Nachwuchswissenschaftlern aus 101 Ländern, die ausgewählt wurden, am Lindau Nobel Laureate Meeting vom 28. Juni – 3. Juli 2020 in Lindau, Deutschland teilzunehmen. Sie wird dort die einzigartige Gelegenheit haben, rund 70 Nobelpreisträger zu treffen. Seit 1951 ist das Meeting eine großartige Gelegenheit für generationsübergreifenden und interdisziplinären Austausch. An diesem einzigartigen internationalen wissenschaftlichen Forum teilnehmen zu können, ist mit Sicherheit eine großartige und inspirierende Erfahrung.

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News from SSR 2019

Juli 21, 2019

On the Annual Meeting of the Society for the Study of Reproduction (SSR) 2019 in San Jose, California, USA, Dr. David Fleck, Nadine Mundt and Lina Kenzler will present their respective data in oral presentations. Justine Fischoeder will present her data on posters and in a flash talk.

Justine was awarded a Travel Grant from the Male Contraceptive Initiative (MCI), Nadine and Lina each won an Best International Abstract Award.

Nadine won an SSR trainee-travel Award, Lina was awarded the Lalor Foundation Merit Award.

New Publication by Sebastian Malinowski

Juli 20, 2019

Malinowski S, Wolf J, Kuenzel T (2019) Intrinsic and Synaptic Dynamics Contribute to Adaptation in the Core of the Avian Central Nucleus of the Inferior Colliculus. Frontiers in Neural Circuits 13.

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Abstract: The reduction of neuronal responses to repeated stimulus presentation occurs in many sensory neurons, also in the inferior colliculus of birds. The cellular mechanisms that cause response adaptation are not well described. Adaptation must be explicable by changes in the activity of input neurons, short-term synaptic plasticity of the incoming connections, excitability changes of the neuron under consideration or influences of inhibitory or modulatory network connections. Using whole-cell recordings in acute brain slices of the embryonic chicken brain we wanted to understand the intrinsic and synaptic contributions to adaptation in the core of the central nucleus of the inferior colliculus (ICCc). We described two neuron types in the chicken ICCc based on their action potential firing patterns: Phasic/onset neurons showed strong intrinsic adaptation but recovered more rapidly. Tonic/sustained firing neurons had weaker adaptation but often had additional slow components of recovery from adaptation. Morphological analysis suggested two neuron classes, but no physiological parameter aligned with this classification. Chicken ICCc neurons received mostly mixed AMPA- and NMDA-type glutamatergic synaptic inputs. In the majority of ICCc neurons the input synapses underwent short-term depression. With a simulation of the putative population output activity of the chicken ICCc we showed that the different adaptation profiles of the neuron classes could shift the emphasize of stimulus encoding from transients at long intervals to ongoing parts at short intervals. Thus, we report here that description of biophysical and synaptic properties can help to explain adaptive phenomena in central auditory neurons.

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