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Nature Sep 2023Only recently have more specific circuit-probing techniques become available to inform previous reports implicating the rodent hippocampus in orexigenic appetitive...
Only recently have more specific circuit-probing techniques become available to inform previous reports implicating the rodent hippocampus in orexigenic appetitive processing. This function has been reported to be mediated at least in part by lateral hypothalamic inputs, including those involving orexigenic lateral hypothalamic neuropeptides, such as melanin-concentrating hormone. This circuit, however, remains elusive in humans. Here we combine tractography, intracranial electrophysiology, cortico-subcortical evoked potentials, and brain-clearing 3D histology to identify an orexigenic circuit involving the lateral hypothalamus andĀ converging in a hippocampal subregion. We found that low-frequency power is modulated by sweet-fat food cues, and this modulation was specific to the dorsolateral hippocampus. Structural and functional analyses of this circuit in a human cohort exhibiting dysregulated eating behaviour revealed connectivity that was inversely related to body mass index. Collectively, this multimodal approach describes an orexigenic subnetwork within the human hippocampus implicated in obesity and related eating disorders.
Topics: Humans; Body Mass Index; Cohort Studies; Cues; Electrophysiology; Evoked Potentials; Feeding and Eating Disorders; Feeding Behavior; Food; Hippocampus; Obesity; Orexins; Neural Pathways
PubMed: 37648849
DOI: 10.1038/s41586-023-06459-w -
Pflugers Archiv : European Journal of... Dec 2023
Topics: Optogenetics; Physiology
PubMed: 38047968
DOI: 10.1007/s00424-023-02887-9 -
Nature Dec 2023The brain controls nearly all bodily functions via spinal projecting neurons (SPNs) that carry command signals from the brain to the spinal cord. However, a...
The brain controls nearly all bodily functions via spinal projecting neurons (SPNs) that carry command signals from the brain to the spinal cord. However, a comprehensive molecular characterization of brain-wide SPNs is still lacking. Here we transcriptionally profiled a total of 65,002 SPNs, identified 76 region-specific SPN types, and mapped these types into a companion atlas of the whole mouse brain. This taxonomy reveals a three-component organization of SPNs: (1) molecularly homogeneous excitatory SPNs from the cortex, red nucleus and cerebellum with somatotopic spinal terminations suitable for point-to-point communication; (2) heterogeneous populations in the reticular formation with broad spinal termination patterns, suitable for relaying commands related to the activities of the entire spinal cord; and (3) modulatory neurons expressing slow-acting neurotransmitters and/or neuropeptides in the hypothalamus, midbrain and reticular formation for 'gain setting' of brain-spinal signals. In addition, this atlas revealed a LIM homeobox transcription factor code that parcellates the reticulospinal neurons into five molecularly distinct and spatially segregated populations. Finally, we found transcriptional signatures of a subset of SPNs with large soma size and correlated these with fast-firing electrophysiological properties. Together, this study establishes a comprehensive taxonomy of brain-wide SPNs and provides insight into the functional organization of SPNs in mediating brain control of bodily functions.
Topics: Animals; Mice; Gene Expression Profiling; Hypothalamus; Neurons; Neuropeptides; Spinal Cord; Brain; Neural Pathways; Neurotransmitter Agents; Mesencephalon; Reticular Formation; Electrophysiology; Cerebellum; Cerebral Cortex
PubMed: 38092914
DOI: 10.1038/s41586-023-06817-8 -
Human Reproduction Update Jul 2023Regulated cell death is a fundamental component of numerous physiological processes; spanning from organogenesis in utero, to normal cell turnover during adulthood, as... (Review)
Review
BACKGROUND
Regulated cell death is a fundamental component of numerous physiological processes; spanning from organogenesis in utero, to normal cell turnover during adulthood, as well as the elimination of infected or damaged cells throughout life. Quality control through regulation of cell death pathways is particularly important in the germline, which is responsible for the generation of offspring. Women are born with their entire supply of germ cells, housed in functional units known as follicles. Follicles contain an oocyte, as well as specialized somatic granulosa cells essential for oocyte survival. Follicle loss-via regulated cell death-occurs throughout follicle development and life, and can be accelerated following exposure to various environmental and lifestyle factors. It is thought that the elimination of damaged follicles is necessary to ensure that only the best quality oocytes are available for reproduction.
OBJECTIVE AND RATIONALE
Understanding the precise factors involved in triggering and executing follicle death is crucial to uncovering how follicle endowment is initially determined, as well as how follicle number is maintained throughout puberty, reproductive life, and ovarian ageing in women. Apoptosis is established as essential for ovarian homeostasis at all stages of development and life. However, involvement of other cell death pathways in the ovary is less established. This review aims to summarize the most recent literature on cell death regulators in the ovary, with a particular focus on non-apoptotic pathways and their functions throughout the discrete stages of ovarian development and reproductive life.
SEARCH METHODS
Comprehensive literature searches were carried out using PubMed and Google Scholar for human, animal, and cellular studies published until August 2022 using the following search terms: oogenesis, follicle formation, follicle atresia, oocyte loss, oocyte apoptosis, regulated cell death in the ovary, non-apoptotic cell death in the ovary, premature ovarian insufficiency, primordial follicles, oocyte quality control, granulosa cell death, autophagy in the ovary, autophagy in oocytes, necroptosis in the ovary, necroptosis in oocytes, pyroptosis in the ovary, pyroptosis in oocytes, parthanatos in the ovary, and parthanatos in oocytes.
OUTCOMES
Numerous regulated cell death pathways operate in mammalian cells, including apoptosis, autophagic cell death, necroptosis, and pyroptosis. However, our understanding of the distinct cell death mediators in each ovarian cell type and follicle class across the different stages of life remains the source of ongoing investigation. Here, we highlight recent evidence for the contribution of non-apoptotic pathways to ovarian development and function. In particular, we discuss the involvement of autophagy during follicle formation and the role of autophagic cell death, necroptosis, pyroptosis, and parthanatos during follicle atresia, particularly in response to physiological stressors (e.g. oxidative stress).
WIDER IMPLICATIONS
Improved knowledge of the roles of each regulated cell death pathway in the ovary is vital for understanding ovarian development, as well as maintenance of ovarian function throughout the lifespan. This information is pertinent not only to our understanding of endocrine health, reproductive health, and fertility in women but also to enable identification of novel fertility preservation targets.
Topics: Adult; Animals; Female; Humans; Apoptosis; Granulosa Cells; Mammals; Oocytes; Ovarian Follicle; Ovary; Regulated Cell Death; Homeostasis
PubMed: 36857094
DOI: 10.1093/humupd/dmad005 -
Nature Oct 2023Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) can provide long-term symptom relief for treatment-resistant depression (TRD). However, achieving stable... (Clinical Trial)
Clinical Trial
Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) can provide long-term symptom relief for treatment-resistant depression (TRD). However, achieving stable recovery is unpredictable, typically requiring trial-and-error stimulation adjustments due to individual recovery trajectories and subjective symptom reporting. We currently lack objective brain-based biomarkers to guide clinical decisions by distinguishing natural transient mood fluctuations from situations requiring intervention. To address this gap, we used a new device enabling electrophysiology recording to deliver SCC DBS to ten TRD participants (ClinicalTrials.gov identifier NCT01984710). At the study endpoint of 24 weeks, 90% of participants demonstrated robust clinical response, and 70% achieved remission. Using SCC local field potentials available from six participants, we deployed an explainable artificial intelligence approach to identify SCC local field potential changes indicating the patient's current clinical state. This biomarker is distinct from transient stimulation effects, sensitive to therapeutic adjustments and accurate at capturing individual recovery states. Variable recovery trajectories are predicted by the degree of preoperative damage to the structural integrity and functional connectivity within the targeted white matter treatment network, and are matched by objective facial expression changes detected using data-driven video analysis. Our results demonstrate the utility of objective biomarkers in the management of personalized SCC DBS and provide new insight into the relationship between multifaceted (functional, anatomical and behavioural) features of TRD pathology, motivating further research into causes of variability in depression treatment.
Topics: Humans; Artificial Intelligence; Biomarkers; Deep Brain Stimulation; Depression; Depressive Disorder, Major; Electrophysiology; Treatment Outcome; Local Field Potential Measurement; White Matter; Limbic Lobe; Facial Expression
PubMed: 37730990
DOI: 10.1038/s41586-023-06541-3 -
Advances in Physiology Education Dec 2023This is a memoir of my experiences in learning and teaching Physiology. It begins in 1962 when I entered the University of Washington as a medical student and began...
This is a memoir of my experiences in learning and teaching Physiology. It begins in 1962 when I entered the University of Washington as a medical student and began research in a physiology laboratory, which led to a Ph.D. degree in Physiology and Biophysics to go with my M.D. degree in 1968. At this time, both groups of students participated in the same physiology course containing both lectures and laboratories. After postdoctoral research at the NIH and in Cambridge, UK, in 1973 I joined the faculty of the Department of Physiology, University of California, San Francisco where I participated in the teaching of medical students and graduate students for nearly 15 years. By this time, the teaching of medical and graduate students had largely separated. In 1987, I moved to the University of Michigan as Professor and Chair of Physiology where my role in teaching was organizational as well as participatory for the next 35 years. In this work, I compare the teaching of medical students as well as graduate students and focus on how it has changed over this 60-year period. Over this time both medical and graduate Ph.D. education have become more integrative. Medical education is now taught in organ blocks rather than courses, and I participated in organizing the teaching of the gastrointestinal block. At Michigan, there is no longer a separate medical school class in Physiology, and graduate students enter a combined, "Program in Biomedical Science" for a year before choosing a mentor and department. Teaching remains an important part of the career of academic physiologists. It is important for schools offering the Ph.D. to provide instruction and experience in teaching. The American Physiology Society has developed new programs to assist teachers and many universities have centers on learning and teaching.
Topics: Humans; Faculty; Education, Medical; Students, Medical; Education, Graduate; Mentors; Teaching; Physiology
PubMed: 37498551
DOI: 10.1152/advan.00094.2023 -
Frontiers in Endocrinology 2023
Topics: Child; Humans; Endocrinology
PubMed: 37388213
DOI: 10.3389/fendo.2023.1233451 -
Annual Review of Neuroscience Jul 2023How neurons detect the direction of motion is a prime example of neural computation: Motion vision is found in the visual systems of virtually all sighted animals, it is... (Review)
Review
How neurons detect the direction of motion is a prime example of neural computation: Motion vision is found in the visual systems of virtually all sighted animals, it is important for survival, and it requires interesting computations with well-defined linear and nonlinear processing steps-yet the whole process is of moderate complexity. The genetic methods available in the fruit fly and the charting of a connectome of its visual system have led to rapid progress and unprecedented detail in our understanding of how neurons compute the direction of motion in this organism. The picture that emerged incorporates not only the identity, morphology, and synaptic connectivity of each neuron involved but also its neurotransmitters, its receptors, and their subcellular localization. Together with the neurons' membrane potential responses to visual stimulation, this information provides the basis for a biophysically realistic model of the circuit that computes the direction of visual motion.
Topics: Animals; Motion Perception; Visual Pathways; Drosophila; Vision, Ocular; Neurons; Photic Stimulation
PubMed: 37428604
DOI: 10.1146/annurev-neuro-080422-111929 -
Scientific Data Oct 2023As data sharing has become more prevalent, three pillars - archives, standards, and analysis tools - have emerged as critical components in facilitating effective data... (Review)
Review
As data sharing has become more prevalent, three pillars - archives, standards, and analysis tools - have emerged as critical components in facilitating effective data sharing and collaboration. This paper compares four freely available intracranial neuroelectrophysiology data repositories: Data Archive for the BRAIN Initiative (DABI), Distributed Archives for Neurophysiology Data Integration (DANDI), OpenNeuro, and Brain-CODE. The aim of this review is to describe archives that provide researchers with tools to store, share, and reanalyze both human and non-human neurophysiology data based on criteria that are of interest to the neuroscientific community. The Brain Imaging Data Structure (BIDS) and Neurodata Without Borders (NWB) are utilized by these archives to make data more accessible to researchers by implementing a common standard. As the necessity for integrating large-scale analysis into data repository platforms continues to grow within the neuroscientific community, this article will highlight the various analytical and customizable tools developed within the chosen archives that may advance the field of neuroinformatics.
Topics: Neurophysiology; Databases, Factual; Information Dissemination
PubMed: 37857685
DOI: 10.1038/s41597-023-02614-0 -
Minerva Endocrinology Mar 2024
Topics: Humans; COVID-19; Endocrinology; Periodicals as Topic
PubMed: 38536096
DOI: 10.23736/S2724-6507.24.04199-X