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Baas, D.

Publications and source records attributed to Baas, D..

3 recordsLinked to original sources

Melatonin modulates habituation learning via the convergent action of two MT1-type receptors.

Melatonin is a hormone produced by the pineal gland and retina, with roles in sleep and circadian rhythms as well as other neuronal processes, including the regulation of learning and memory. Using larval zebrafish, we previously identified Melatonin as a potent modulator of habituation learning: the progressive suppression of responses to a repeated stimulus. Here we have extended these analyses and have found that Melatonin has strong effects on separate aspects of habituation learning: it potentiates habituation of response probability and latency, while simultaneously inhibiting habituation of movement amplitude and duration. We performed a systematic CRISPR mutagenesis of all six zebrafish Melatonin receptors, and found that only two MT1-type receptors (Mtnr1aa and Mtnr1al) are required for Melatonin's effects on habituation. These receptors showed a cooperative interaction, with each individual mutant showing reduced sensitivity to Melatonin, and mtnr1aa;mtnr1al double mutants showing complete insensitivity. To map where these receptors act, we used whole-brain activity mapping. Despite distinct footprints, both perturbed a shared set of brain areas, including the torus longitudinalis, cerebellum, and preoptic area, with the double mutant producing the most extensive phenotype by combining and expanding the effects seen in each single mutant. Thus, we propose that two MT1-type receptors act at overlapping circuit nodes to reinforce Melatonin's bidirectional control of learning.

neuroscience↗

Estradiol promotes habituation learning via an unidentified target, bypassing the suppressive effects of established Estrogen Receptors

Habituating to the constant stimuli in the environment is a critical learning process conserved across species. We use a larval zebrafish visual response to sudden darkness as a model for studying habituation learning, where zebrafish reduce their responses to repeated stimulations. In this paradigm, treatment with estradiol strongly increases learning rate, resulting in more strongly suppressed responses. We used mutant lines for the Estrogen Receptors (esr1, esr2a, esr2b, gper1) in an attempt to identify the receptor(s) mediating these effects. These experiments failed to identify a necessary receptor (or combination of receptors). Surprisingly, esr1, esr2a, and gper1 mutants showed weak but consistent increases in habituation, indicating these receptors suppress habituation learning. These experiments demonstrate that estradiol is a complex modulator of learning in our model, where the learning-promoting effects are mediated by an unidentified estradiol target, and the classical Estrogen Receptors act in competition to subtly suppress learning.

neuroscience↗

Biophysical ordering transitions underlie genome 3D re-organization during cricket spermiogenesis.

Spermiogenesis is a radical process of differentiation whereby sperm cells acquire a compact and specialized morphology to cope with the constraints of sexual reproduction while preserving their main cargo, an intact copy of the paternal genome. In animals, this often involves the replacement of most histones by sperm-specific nuclear basic proteins (SNBPs). Yet, how the SNBP-structured genome achieves compaction and accommodates shaping remain largely unknown. Here, we exploited confocal, electron and super-resolution microscopy observations, coupled with polymer modeling simulations to identify the higher-order architecture of sperm chromatin in the needle-shaped nucleus of the emerging model cricket Gryllus bimaculatus. Accompanying spermatid differentiation and shaping, the SNBP-based genome was strikingly reorganized as ~25nm-thick fibers orderly coiled along the elongated nucleus axis. This chromatin spool was further found to achieve large-scale helical twisting in the final stages of spermiogenesis, favoring its ultracompaction. Through a combination of microscopy observations and polymer simulations, we revealed that these dramatic transitions may be recapitulated by a surprisingly simple biophysical principle based on a nucleated rigidification of chromatin linked to the histone-to-SNBP transition within a confined nuclear space. Our work highlights a unique, liquid crystal-like mode of higher-order genome organization in ultracompact cricket sperm completely distinct from nucleosomal chromatin, and establishes a multidisciplinary methodological framework to explore the diversity of non-canonical modes of DNA organization. SIGNIFICANCE STATEMENTAnimal sperm cells are highly compact and atypically shaped compared to other cell types. How DNA is packaged and organized in the 3D space of sperm cell nuclei to cope with these constraints is poorly understood. In this work, we identified an original and elegant solution to this problem in crickets, whereby DNA fibers orderly spool and twist to fit into ultracompact, needle-shaped sperm cells. To understand this reorganization, we modeled DNA fibers in the nucleus as polymers and found that a relatively simple mechanism through which fibers become more rigid bit by bit can largely recapitulate our observations. Our multidisciplinary work highlights a simple solution to compact DNA to extreme levels in specialized nuclei.

cell biology↗