scholarly journals CA1 pyramidal cell diversity is rootedin the time of neurogenesis

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Davide Cavalieri ◽  
Alexandra Angelova ◽  
Anas Islah ◽  
Catherine Lopez ◽  
Marco Bocchio ◽  
...  

Cellular diversity supports the computational capacity and flexibility of cortical circuits. Accordingly, principal neurons at the CA1 output node of the murine hippocampus are increasingly recognized as a heterogeneous population. Their genes, molecular content, intrinsic morphophysiology, connectivity, and function seem to segregate along the main anatomical axes of the hippocampus. Since these axes reflect the temporal order of principal cell neurogenesis, we directly examined the relationship between birthdate and CA1 pyramidal neuron diversity, focusing on the ventral hippocampus. We used a genetic fate-mapping approach that allowed tagging three groups of age-matched principal neurons: pioneer, early- and late-born. Using a combination of neuroanatomy, slice physiology, connectivity tracing and cFos staining in mice, we show that birthdate is a strong predictor of CA1 principal cell diversity. We unravel a subpopulation of pioneer neurons recruited in familiar environments with remarkable positioning, morpho-physiological features, and connectivity. Therefore, despite the expected plasticity of hippocampal circuits, given their role in learning and memory, the diversity of their main components is also partly determined at the earliest steps of development.

2021 ◽  
Author(s):  
Davide Cavalieri ◽  
Alexandra Angelova ◽  
Anas Islah ◽  
Catherine Lopez ◽  
Agnes Baude ◽  
...  

AbstractCellular diversity supports the computational capacity and flexibility of cortical circuits. Accordingly, principal neurons at the CA1 output node of the hippocampus are increasingly recognized as a heterogeneous population. Their genes, molecular content, intrinsic morpho-physiology, connectivity, and function seem to segregate along the main anatomical axes of the hippocampus. Since these axes reflect the temporal order of principal cell neurogenesis, we directly examined the relationship between birthdate and CA1 pyramidal neuron diversity, focusing on the ventral hippocampus. We used a genetic fate-mapping approach that allowed tagging three groups of age-matched principal neurons: pioneer, early-and late-born. Using a combination of neuroanatomy, slice physiology, connectivity tracing and cFos staining, we show that birthdate is a strong predictor of CA1 principal cell diversity. We unravel a subpopulation of pioneer neurons recruited in familiar environments with remarkable positioning, morpho-physiological features, and connectivity. Therefore, despite the expected plasticity of hippocampal circuits, given their role in learning and memory, the diversity of their main components is significantly predetermined at the earliest steps of development.


Author(s):  
Patricia G. Arscott ◽  
Gil Lee ◽  
Victor A. Bloomfield ◽  
D. Fennell Evans

STM is one of the most promising techniques available for visualizing the fine details of biomolecular structure. It has been used to map the surface topography of inorganic materials in atomic dimensions, and thus has the resolving power not only to determine the conformation of small molecules but to distinguish site-specific features within a molecule. That level of detail is of critical importance in understanding the relationship between form and function in biological systems. The size, shape, and accessibility of molecular structures can be determined much more accurately by STM than by electron microscopy since no staining, shadowing or labeling with heavy metals is required, and there is no exposure to damaging radiation by electrons. Crystallography and most other physical techniques do not give information about individual molecules.We have obtained striking images of DNA and RNA, using calf thymus DNA and two synthetic polynucleotides, poly(dG-me5dC)·poly(dG-me5dC) and poly(rA)·poly(rU).


Author(s):  
J. Donald Boudreau ◽  
Eric Cassell ◽  
Abraham Fuks

This book reimagines medical education and reconstructs its design. It originates from a reappraisal of the goals of medicine and the nature of the relationship between doctor and patient. The educational blueprint outlined is called the “Physicianship Curriculum” and rests on two linchpins. First is a new definition of sickness: Patients know themselves to be ill when they cannot pursue their purposes and goals in life because of impairments in functioning. This perspective represents a bulwark against medical attention shifting from patients to diseases. The curriculum teaches about patients as functional persons, from their anatomy to their social selves, starting in the first days of the educational program and continuing throughout. Their teaching also rests on the rock-solid grounding of medicine in the sciences and scientific understandings of disease and function. The illness definition and knowledge base together create a foundation for authentic patient-centeredness. Second, the training of physicians depends on and culminates in development of a unique professional identity. This is grounded in the historical evolution of the profession, reaching back to Hippocrates. It leads to reformulation of the educational process as clinical apprenticeships and moral mentorships. “Rebirth” in the title suggests that critical ingredients of medical education have previously been articulated. The book argues that the apprenticeship model, as experienced, enriched, taught, and exemplified by William Osler, constitutes a time-honored foundation. Osler’s “natural method of teaching the subject of medicine” is a precursor to the Physicianship Curriculum.


2021 ◽  
pp. 147490412110097
Author(s):  
Niels Åkerstrøm Andersen ◽  
Justine Grønbæk Pors

Taking a point of departure in the paradoxical fact that the increase in educational knowledge leads to an increase in uncertainty for educational organisations, this article explores how uncertainty and contingency have increasingly become an integral part of school governance. The article draws on Niklas Luhmann’s theory of ‘World Society’ as a functional differentiated society providing a range of different symbolic media for educational organisations. To trace the increase in the complexity of governing, we provide a historical account of the shifting couplings between schools and function systems. We show how the school becomes linked to an increasing number of symbolic media so that education becomes only one out of many other concerns. The article studies the consequences these shifting couplings have for how schools are governed and how they are expected to self-manage their relationship to different function systems. The article adds to existing studies of how education has become more and more differentiated with the argument that this has also led to new forms of couplings between schools and the education system with a number of important implications for the teaching profession.


Author(s):  
Gianmarco Secco ◽  
◽  
Marzia Delorenzo ◽  
Francesco Salinaro ◽  
Caterina Zattera ◽  
...  

AbstractBedside lung ultrasound (LUS) can play a role in the setting of the SarsCoV2 pneumonia pandemic. To evaluate the clinical and LUS features of COVID-19 in the ED and their potential prognostic role, a cohort of laboratory-confirmed COVID-19 patients underwent LUS upon admission in the ED. LUS score was derived from 12 fields. A prevalent LUS pattern was assigned depending on the presence of interstitial syndrome only (Interstitial Pattern), or evidence of subpleural consolidations in at least two fields (Consolidation Pattern). The endpoint was 30-day mortality. The relationship between hemogasanalysis parameters and LUS score was also evaluated. Out of 312 patients, only 36 (11.5%) did not present lung involvment, as defined by LUS score < 1. The majority of patients were admitted either in a general ward (53.8%) or in intensive care unit (9.6%), whereas 106 patients (33.9%) were discharged from the ED. In-hospital mortality was 25.3%, and 30-day survival was 67.6%. A LUS score > 13 had a 77.2% sensitivity and a 71.5% specificity (AUC 0.814; p < 0.001) in predicting mortality. LUS alterations were more frequent (64%) in the posterior lower fields. LUS score was related with P/F (R2 0.68; p < 0.0001) and P/F at FiO2 = 21% (R2 0.59; p < 0.0001). The correlation between LUS score and P/F was not influenced by the prevalent ultrasound pattern. LUS represents an effective tool in both defining diagnosis and stratifying prognosis of COVID-19 pneumonia. The correlation between LUS and hemogasanalysis parameters underscores its role in evaluating lung structure and function.


Blood ◽  
1948 ◽  
Vol 3 (7) ◽  
pp. 729-754 ◽  
Author(s):  
WILLIAM N. VALENTINE ◽  
CHARLES G. CRADDOCK ◽  
JOHN S. LAWRENCE

Abstract The hormonal control through the hypophyseo-adrenal cortical system of lymphoid tissue structure and function is an important concept. We cannot at the present time regard that the concept is established fact. Final judgment must await additional work and the clarification of some of the inconsistencies which appear to exist. It seems reasonable that lymphoid tissue is one of the end organs of adrenal cortical hormone and that it may perhaps play a role in the response of the organism to stress. It seems quite clear that the sugar hormone of the adrenal cortex is capable of producing structural alterations in lymphoid tissue. Change in thoracic duct lymphocyte numbers as a result of augmentation in the amount of available adrenal cortical hormone is at present controversial. Experiments in this laboratory have failed to demonstrate it. The production of lymphopenia, at least in some species and possibly in man, by increasing available sugar hormone is supported by some evidence. The exact mechanism of production of lymphopenia is open to question, its relationship to changes in lymphoid tissue structure being one of inference. The converse situation—absolute lympocytosis resulting from deprivation of adrenal cortical hormone—is the subject of controversial reports. At best, it must be admitted that relatively slight alterations from the accepted normal range of lymphocyte values occur in the adrenal insufficient organism. Changes in plasma gamma globulins and antibody titers associated with changes in the amount of available cortical hormone are reported. It should be clarified whether such changes have necessarily resulted from lymphocyte dissolution or are related to other of the variegated actions of adrenal cortical hormone. The relationship of adrenal cortical hormone to lymphoid tissue and lymphocytes and the relationship of the latter to the response of the organism to stress must indeed be complex. It is reasonably well established that the life span of the lymphocyte is very short indeed1,58,22 and each lymphocyte presumably liberates its metabolically important contents within a few hours at the most. If stress continues for any period of time, as often it does, it is difficult to visualize the wisdom of interfering with the production of metabolically vital substances in order to secure the transient benefits of lymphoid tissue dissolution. It is also somewhat difficult to regard as proved that the various changes reported after hormone augmentation or deprivation necessarily represent the normal mechanism by which these factors are regulated and kept within physiologic limits. More investigations are required to answer such questions and to further elucidate the interrelationship of the adrenal cortex and lymphoid tissues.


2020 ◽  
Author(s):  
Jelle A. van Dijk ◽  
Alessio Fracasso ◽  
Natalia Petridou ◽  
Serge O. Dumoulin

AbstractAdvancements in ultra-high field (7 T and higher) magnetic resonance imaging (MRI) scanners have made it possible to investigate both the structure and function of the human brain at a sub-millimeter scale. As neuronal feedforward and feedback information arrives in different layers, sub-millimeter functional MRI has the potential to uncover information processing between cortical micro-circuits across cortical depth, i.e. laminar fMRI. For nearly all conventional fMRI analyses, the main assumption is that the relationship between local neuronal activity and the blood oxygenation level dependent (BOLD) signal adheres to the principles of linear systems theory. For laminar fMRI, however, directional blood pooling across cortical depth stemming from the anatomy of the cortical vasculature, potentially violates these linear system assumptions, thereby complicating analysis and interpretation. Here we assess whether the temporal additivity requirement of linear systems theory holds for laminar fMRI. We measured responses elicited by viewing stimuli presented for different durations and evaluated how well the responses to shorter durations predicted those elicited by longer durations. We find that BOLD response predictions are consistently good predictors for observed responses, across all cortical depths, and in all measured visual field maps (V1, V2, and V3). Our results suggest that the temporal additivity assumption for linear systems theory holds for laminar fMRI. We thus show that the temporal additivity assumption holds across cortical depth for sub-millimeter gradient-echo BOLD fMRI in early visual cortex.


2009 ◽  
Vol 17 (4) ◽  
pp. 422-447 ◽  
Author(s):  
Bruce Longenecker

AbstractThe aphorism 'context is everything' has been a guiding principle in many studies of Jesus' parabolic sayings. This is true, for instance, of studies attempting to recover a parable's significance in relation to the ministry of Jesus of Nazareth, or in relation to its literary placement and function, or in relation to its polyvalent potential. It is also true of this study, which examines Jesus' narrative of the Samaritan—usually referred to as the 'parable of the good Samaritan'. It suggests that, when the Samaritan story is placed within a certain contextual configuration, its narrative features align themselves in ways that have either been conspicuously neglected or consciously avoided in the history of the story's interpretation. Rather than neglecting or avoiding the significance of these narrative features, this essay seeks to exploit their interpretative significance in a fresh manner, entertaining possibilities of meaning beyond the Lukan interpretative framework. In particular, consideration is given to the relationship between the Samaritan and the innkeeper as representing an exceptional partnership that testifies to the reign of God in making each party vulnerable to loss while promoting goodness towards others.


2017 ◽  
Vol 14 (135) ◽  
pp. 20170484 ◽  
Author(s):  
Matthew D. B. Jackson ◽  
Salva Duran-Nebreda ◽  
George W. Bassel

Multicellularity and cellular cooperation confer novel functions on organs following a structure–function relationship. How regulated cell migration, division and differentiation events generate cellular arrangements has been investigated, providing insight into the regulation of genetically encoded patterning processes. Much less is known about the higher-order properties of cellular organization within organs, and how their functional coordination through global spatial relations shape and constrain organ function. Key questions to be addressed include: why are cells organized in the way they are? What is the significance of the patterns of cellular organization selected for by evolution? What other configurations are possible? These may be addressed through a combination of global cellular interaction mapping and network science to uncover the relationship between organ structure and function. Using this approach, global cellular organization can be discretized and analysed, providing a quantitative framework to explore developmental processes. Each of the local and global properties of integrated multicellular systems can be analysed and compared across different tissues and models in discrete terms. Advances in high-resolution microscopy and image analysis continue to make cellular interaction mapping possible in an increasing variety of biological systems and tissues, broadening the further potential application of this approach. Understanding the higher-order properties of complex cellular assemblies provides the opportunity to explore the evolution and constraints of cell organization, establishing structure–function relationships that can guide future organ design.


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