Image‐based High‐content Screening – A View from Basic Sciences

Lipp, Peter; Kaestner, Lars

doi:10.1002/9783527609321.ch6

Cited by 11 publications

(4 citation statements)

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“…Intellicage (NewBehavior AG, Zurich, Switzerland) is an automated device that allows housing, performance and measurements of specific tasks in a fully automated manner, removing the need for a human operator and operator-derived bias [24,25]. Mice were divided into two groups: the “control” treated with 0.1% (w/v) saccharine in the drinking water and the “experimental group” with 0.1% (w/v) saccharin supplemented with 0.08% (w/v) fluoxetine in the drinking water.…”

Section: Methodsmentioning

confidence: 99%

Activation of TrkB in Parvalbumin interneurons is required for the promotion of reversal learning in spatial and fear memory by antidepressants

Jetsonen

Didio

Winkel

et al. 2022

Preprint

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Critical period-like plasticity (iPlasticity) can be reinstated in the adult brain by several interventions, including drugs and optogenetic modifications. We have demonstrated that a combination of iPlasticity with optimal training improves behaviors related to neuropsychiatric disorders. In this context, the activation of TrkB, a receptor for BDNF, in Parvalbumin positive (PV+) interneurons has a pivotal role in cortical network changes. However, it is unknown if the activation of TrkB in PV+ interneurons is important for other plasticity-related behaviors, especially for learning and memory. Here, using mice with heterozygous conditional TrkB deletion in PV+ interneurons (PV-TrkB hCKO) in Intellicage and fear erasure paradigms, we show that chronic treatment with fluoxetine, a widely prescribed antidepressant drug that is known to promote the activation of TrkB, enhances behavioral flexibility in spatial and fear memory, largely depending on the expression of the TrkB receptor in PV+ interneurons. In addition, hippocampal long-term potentiation (LTP) was enhanced by chronic treatment with fluoxetine in wild-type mice, but not in PV-TrkB hCKO mice. Transcriptomic analysis of PV+ interneurons after fluoxetine treatment indicated intrinsic changes in synaptic formation and downregulation of enzymes involved in perineuronal net (PNN) formation. Consistently, immunohistochemistry has shown that the fluoxetine treatment alters PV expression and reduces PNNs in PV+ interneurons, and here we show that TrkB expression in PV+ interneurons is required for these effects. Together, our results provide molecular and network mechanisms for the induction of critical period-like plasticity in adulthood.

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Section: Methodsmentioning

confidence: 99%

Activation of TrkB in Parvalbumin interneurons is required for the promotion of reversal learning in spatial and fear memory by antidepressants

Jetsonen

Didio

Winkel

et al. 2022

Preprint

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“…It has in common with the two-photon microscopy that fluorophores are excited only in the layers where image generation occurs. This is in contrast to confocal microscopy and other sectioning microscopy methods (Lipp and Kaestner, 2006) and has the advantage to avoid unnecessary photobleaching of the samples.…”

Section: Light-sheet Microscopymentioning

confidence: 99%

Imaging Erythrocyte Sedimentation in Whole Blood

et al. 2022

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The erythrocyte sedimentation rate (ESR) is one of the oldest medical diagnostic tools. However, currently there is some debate on the structure formed by the cells during the sedimentation process. While the conventional view is that erythrocytes sediment as separate aggregates, others have suggested that they form a percolating gel, similar to other colloidal suspensions. However, visualization of aggregated erythrocytes, which would settle the question, has always been challenging. Direct methods usually study erythrocytes in 2D situations or low hematocrit (∼1%). Indirect methods, such as scattering or electric measurements, provide insight on the suspension evolution, but cannot directly discriminate between open or percolating structures. Here, we achieved a direct probing of the structures formed by erythrocytes in blood at stasis. We focused on blood samples at rest with controlled hematocrit of 45%, from healthy donors, and report observations from three different optical imaging techniques: direct light transmission through thin samples, two-photon microscopy and light-sheet microscopy. The three techniques, used in geometries with thickness from 150 μm to 3 mm, highlight that erythrocytes form a continuous network with characteristic cracks, i.e., a colloidal gel. The characteristic distance between the main cracks is of the order of ∼100 μm. A complete description of the structure then requires a field of view of the order of ∼1 mm, in order to obtain a statistically relevant number of structural elements. A quantitative analysis of the erythrocyte related processes and interactions during the sedimentation need a further refinement of the experimental set-ups.

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“…IntelliCage (NewBehavior AG, Zurich, Switzerland) is an automated device that allows housing, performance and measurements of specific tasks in a fully automated manner, removing the need for a human operator and operator-derived bias [24,25]. We used a number of mice that, according to the method described by Charan and Knetharia [26], leads to a more than adequate degree of freedom of the analysis of variance.…”

Section: Intellicage With Chronic Fluoxetine Treatmentmentioning

confidence: 99%

Activation of TrkB in Parvalbumin interneurons is required for the promotion of reversal learning in spatial and fear memory by antidepressants

Jetsonen

Didio

Winkel

et al. 2023

Neuropsychopharmacol.

View full text Add to dashboard Cite

Critical period-like plasticity (iPlasticity) can be reinstated in the adult brain by several interventions, including drugs and optogenetic modifications. We have demonstrated that a combination of iPlasticity with optimal training improves behaviors related to neuropsychiatric disorders. In this context, the activation of TrkB, a receptor for BDNF, in Parvalbumin-positive (PV+) interneurons has a pivotal role in cortical network changes. However, it is unknown if the activation of TrkB in PV+ interneurons is important for other plasticity-related behaviors, especially for learning and memory. Here, using mice with heterozygous conditional TrkB deletion in PV+ interneurons (PV-TrkB hCKO) in IntelliCage and fear erasure paradigms, we show that chronic treatment with fluoxetine, a widely prescribed antidepressant drug that is known to promote the activation of TrkB, enhances behavioral flexibility in spatial and fear memory, largely depending on the expression of the TrkB receptor in PV+ interneurons. In addition, hippocampal long-term potentiation was enhanced by chronic treatment with fluoxetine in wild-type mice, but not in PV-TrkB hCKO mice. Transcriptomic analysis of PV+ interneurons after fluoxetine treatment indicated intrinsic changes in synaptic formation and downregulation of enzymes involved in perineuronal net formation. Consistently, immunohistochemistry has shown that the fluoxetine treatment alters PV expression and reduces PNNs in PV+ interneurons, and here we show that TrkB expression in PV+ interneurons is required for these effects. Together, our results provide molecular and network mechanisms for the induction of critical period-like plasticity in adulthood.

show abstract

Image‐based High‐content Screening – A View from Basic Sciences

Cited by 11 publications

References 0 publications

Activation of TrkB in Parvalbumin interneurons is required for the promotion of reversal learning in spatial and fear memory by antidepressants

Activation of TrkB in Parvalbumin interneurons is required for the promotion of reversal learning in spatial and fear memory by antidepressants

Imaging Erythrocyte Sedimentation in Whole Blood

Activation of TrkB in Parvalbumin interneurons is required for the promotion of reversal learning in spatial and fear memory by antidepressants

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