The understanding of the structural and dynamic complexity of mammalian brains is greatly facilitated by computer simulations. We present here a detailed large-scale thalamocortical model based on experimental measures in several mammalian species. The model spans three anatomical scales. (i) It is based on global (white-matter) thalamocortical anatomy obtained by means of diffusion tensor imaging (DTI) of a human brain. (ii) It includes multiple thalamic nuclei and six-layered cortical microcircuitry based on in vitro labeling and three-dimensional reconstruction of single neurons of cat visual cortex. (iii) It has 22 basic types of neurons with appropriate laminar distribution of their branching dendritic trees. The model simulates one million multicompartmental spiking neurons calibrated to reproduce known types of responses recorded in vitro in rats. It has almost half a billion synapses with appropriate receptor kinetics, short-term plasticity, and long-term dendritic spike-timing-dependent synaptic plasticity (dendritic STDP). The model exhibits behavioral regimes of normal brain activity that were not explicitly built-in but emerged spontaneously as the result of interactions among anatomical and dynamic processes. We describe spontaneous activity, sensitivity to changes in individual neurons, emergence of waves and rhythms, and functional connectivity on different scales.
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http://dx.doi.org/10.1073/pnas.0712231105 | DOI Listing |
Proc Natl Acad Sci U S A
February 2025
State Key Laboratory of Genetic Engineering, School of Life Sciences, Liver Cancer Institute of Zhongshan Hospital, Fudan University, Shanghai 200438, China.
Aging is a complex process that affects multiple organs, and the discovery of a pharmacological approach to ameliorate aging is considered the Holy Grail of medicine. Here, we performed an N-ethyl-N-nitrosourea forward genetic screening in zebrafish and identified an accelerated aging mutant named (), harboring a mutation in the - () gene. Loss of leads to a short lifespan and age-related characteristics in the intestine of zebrafish embryos, such as cellular senescence, genomic instability, and epigenetic alteration.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Information Technologies, Faculty of Economics and Management, Czech University of Life Sciences Prague, Prague, Czech Republic.
Social networks are a battlefield for political propaganda. Protected by the anonymity of the internet, political actors use computational propaganda to influence the masses. Their methods include the use of synchronized or individual bots, multiple accounts operated by one social media management tool, or different manipulations of search engines and social network algorithms, all aiming to promote their ideology.
View Article and Find Full Text PDFG3 (Bethesda)
January 2025
School of Life Sciences, Center for Evolution & Medicine, Arizona State University, Tempe, AZ 85281, USA.
The demographic history of a population, and the distribution of fitness effects (DFE) of newly arising mutations in functional genomic regions, are fundamental factors dictating both genetic variation and evolutionary trajectories. Although both demographic and DFE inference has been performed extensively in humans, these approaches have generally either been limited to simple demographic models involving a single population, or, where a complex population history has been inferred, without accounting for the potentially confounding effects of selection at linked sites. Taking advantage of the coding-sparse nature of the genome, we propose a 2-step approach in which coalescent simulations are first used to infer a complex multi-population demographic model, utilizing large non-functional regions that are likely free from the effects of background selection.
View Article and Find Full Text PDFBrief Bioinform
November 2024
Department of Dermatology, Daping Hospital, Army Medical University, No. 10, Changjiang Branch Road, Yuzhong District, Chongqing 400042, China.
Psoriasis affects a significant proportion of the worldwide population and causes an extremely heavy psychological and physical burden. The existing therapeutic schemes have many deficiencies such as limited efficacies and various side effects. Therefore, novel ways of treating psoriasis are urgently needed.
View Article and Find Full Text PDFElife
January 2025
Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, United States.
Sensory experience during developmental critical periods has lifelong consequences for circuit function and behavior, but the molecular and cellular mechanisms through which experience causes these changes are not well understood. The antennal lobe houses synapses between olfactory sensory neurons (OSNs) and downstream projection neurons (PNs) in stereotyped glomeruli. Many glomeruli exhibit structural plasticity in response to early-life odor exposure, indicating a general sensitivity of the fly olfactory circuitry to early sensory experience.
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