Biology subjects

Kruk, K.

Publications and source records attributed to Kruk, K..

4 recordsLinked to original sources

bioRxiv2025

The Median Preoptic Nucleus is a Key Site for Estradiol Regulation of Sleep-Wake Behaviors in Females Rats

Study ObjectivesWomen experience more sleep disruptions than men, particularly during hormonal transitions such as puberty, pregnancy, and menopause. This study investigated the role of estradiol (E2) in regulating sleep-wake behavior in female rats and identified the brain regions involved. MethodsUsing an exogenous E2 replacement model in ovariectomized rats, we assessed changes in sleep-wake patterns via EEG/EMG telemetry. The effects of E2 and progesterone, selective estrogen receptor agonists, and direct brain infusions of E2 and receptor antagonists were evaluated. ResultsE2 administration increased wakefulness, reduced non-rapid eye movement (NREM) and rapid eye movement (REM) sleep, and decreased NREM slow-wave activity (SWA), predominantly during the dark phase. These effects required both estrogen receptor alpha (ER) and beta (ER{beta}) activation and were mediated by estrogen receptor signaling within the median preoptic nucleus (MnPO). Direct infusion of E2 into the MnPO was sufficient to replicate systemic effects, while local infusion of the pure estrogen receptor antagonist ICI 182,780 (Fulvestrant) attenuated them. Progesterone did not augment E2s actions, and males showed no sleep-wake changes in response to E2, highlighting sex-specific mechanisms. ConclusionsThe MnPO is a critical site where E2 regulates sleep-wake behavior. These findings provide a neurobiological framework for understanding how ovarian hormones contribute to sleep disruptions in women, offering potential therapeutic targets for sleep disorders related to hormonal changes. Statement of significanceSleep disturbances disproportionately affect women, particularly during hormonal transitions such as puberty, pregnancy, and menopause. Despite this, the underlying mechanisms by which estradiol (E2) influences sleep-wake behavior have remained unclear. This study identifies the median preoptic nucleus (MnPO) as a critical site where E2 signaling regulates sleep-wake patterns in female rats. Our findings demonstrate that E2 increases wakefulness and reduces both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep, with effects primarily observed during the dark phase. By showing that local E2 signaling in the MnPO is both necessary and sufficient for these changes, this work offers a novel neurobiological framework for understanding how fluctuations in ovarian hormones contribute to sleep disruptions in women. These insights lay the groundwork for developing targeted therapies to improve sleep health in women, particularly those experiencing hormonal changes.

neuroscience↗

bioRxiv2025

Distributed control circuits across a brain-and-cord connectome

Just as genomes revolutionized molecular genetics, connectomes (maps of neurons and synapses) are transforming neuroscience. To date, the only species with complete connectomes are worms1-3 and sea squirts4 (103-104 synapses). By contrast, the fruit fly is more complex (108 synaptic connections), with a brain that supports learning and spatial memory5,6 and an intricate ventral nerve cord analogous to the vertebrate spinal cord7-11. Here we report the first densely reconstructed adult fly connectome that unites the brain and ventral nerve cord, and we leverage this resource to investigate principles of neural control. We show that effector neurons (motor neurons, endocrine cells and efferent neurons targeting the viscera) are primarily influenced by sensory neurons in the same body part, forming local feedback loops. These local loops are linked by long-range circuits involving ascending and descending neurons organized into behavior-centric modules. Single ascending and descending neurons are often positioned to influence the voluntary movements of multiple body parts, together with the endocrine cells or visceral organs that support those movements. Brain regions involved in learning and navigation supervise these circuits. These results reveal an architecture that is distributed, parallelized and embodied, reminiscent of distributed control architectures in engineered systems12,13.

neuroscience↗

bioRxiv2023

Neuronal "parts list" and wiring diagram for a visual system

A catalog of neuronal cell types has often been called a "parts list" of the brain, and regarded as a prerequisite for understanding brain function. In the optic lobe of Drosophila, rules of connectivity between cell types have already proven essential for understanding fly vision. Here we analyze the fly connectome to complete the list of cell types intrinsic to the optic lobe, as well as the rules governing their connectivity. We more than double the list of known types. Most new cell types contain between 10 and 100 cells, and integrate information over medium distances in the visual field. Some existing type families (Tm, Li, and LPi) at least double in number of types. We introduce a new Sm interneuron family, which contains more types than any other, and three new families of cross-neuropil types. Self-consistency of cell types is demonstrated through automatic assignment of cells to types by distance in high-dimensional feature space, and further validation is provided by algorithms that select small subsets of discriminative features. Cell types with similar connectivity patterns divide into clusters that are interpretable in terms of motion, object, and color vision. Our work showcases the advantages of connectomic cell typing: complete and unbiased sampling, a rich array of features based on connectivity, and reduction of the connectome to a drastically simpler wiring diagram of cell types, with immediate relevance for brain function and development.

neuroscience↗

bioRxiv2023

Neuronal wiring diagram of an adult brain

Connections between neurons can be mapped by acquiring and analyzing electron microscopic (EM) brain images. In recent years, this approach has been applied to chunks of brains to reconstruct local connectivity maps that are highly informative, yet inadequate for understanding brain function more globally. Here, we present the first neuronal wiring diagram of a whole adult brain, containing 5x107 chemical synapses between [~]130,000 neurons reconstructed from a female Drosophila melanogaster. The resource also incorporates annotations of cell classes and types, nerves, hemilineages, and predictions of neurotransmitter identities. Data products are available by download, programmatic access, and interactive browsing and made interoperable with other fly data resources. We show how to derive a projectome, a map of projections between regions, from the connectome. We demonstrate the tracing of synaptic pathways and the analysis of information flow from inputs (sensory and ascending neurons) to outputs (motor, endocrine, and descending neurons), across both hemispheres, and between the central brain and the optic lobes. Tracing from a subset of photoreceptors all the way to descending motor pathways illustrates how structure can uncover putative circuit mechanisms underlying sensorimotor behaviors. The technologies and open ecosystem of the FlyWire Consortium set the stage for future large-scale connectome projects in other species.

neuroscience↗