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* Context.--The purpose of this review was to compare 3 coronavirus diseases, including severe acute respiratory syndrome, Middle East respiratory syndrome, and COVID-19 caused by SARS-CoV, MERS-CoV, and SARS-CoV-2 viruses, respectively. Objective.--To cover the following topics: clinical considerations, viral characteristics, pathology, immune response, pathogenesis, and the prognosis associated with each coronavirus disease in humans. Data Sources.--Clinically, flu-like symptoms are usual at the time of presentation for all 3 diseases, but these vary from asymptomatic to severe multisystem involvement. The pathology associated with symptomatic severe acute respiratory syndrome and COVID-19 has been well described, the most prominent of which is diffuse alveolar damage. The immune response to each of these viruses is highly complex and includes both humoral and cellular components that can have a significant impact on prognosis. In severe cases of COVID-19, a dysregulated innate host immune system can initiate a hyperinflammatory syndrome dominated by endothelial dysfunction that can lead to a hypercoagulable state with microthrombi, resulting in a systemic microvascular and macrovascular disease. Conclusions.--The severe acute respiratory syndrome and Middle East respiratory syndrome epidemics have been limited, involving approximately 8000 and 2500 individuals, respectively. In contrast, COVID-19 has resulted in a worldwide pandemic with more than 177 million cases and 3.9 million deaths as of June 15, 2021, and fatality rates ranging from less than 0.1% to approximately 10% depending upon the country. Ending on a positive note, the development of a number of vaccines, at least 6 of which now are in clinical use, should mitigate and eventually control the devastating COVID-19 pandemic. doi: 10.5858/arpa.2020-0820-SA, The purpose of this review was to compare the following 3 coronavirus diseases: severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and Coronavirus Disease 2019 (COVID-19) with an [...]

The retrosplenial cortex (RSC) is part of a network of interconnected cortical, hippocampal, and thalamic structures harboring spatially modulated neurons. The RSC contains head direction cells and connects to the parahippocampal region and anterior thalamus. Manipulations of the RSC can affect spatial and contextual tasks. A considerable amount of evidence implicates the role of the RSC in spatial navigation, but it is unclear whether this structure actually encodes or stores spatial information. We used a transgenic mouse in which the expression of green fluorescent protein was under the control of the immediate early gene c-fos promoter as well as time-lapse two-photon in vivo imaging to monitor neuronal activation triggered by spatial learning in the Morris water maze. We uncovered a repetitive pattern of cell activation in the RSC consistent with the hypothesis that during spatial learning an experience-dependent memory trace is formed in this structure. In support of this hypothesis, we also report three other observations. First, temporary RSC inactivation disrupts performance in a spatial learning task. Second, we show that overexpressing the transcription factor CREB in the RSC with a viral vector, a manipulation known to enhance memory consolidation in other circuits, results in spatial memory enhancements. Third, silencing the viral CREB-expressing neurons with the allatostatin system occludes the spatial memory enhancement. Taken together, these results indicate that the retrosplenial cortex engages in the formation and storage of memory traces for spatial information.

We provide a brief (and unabashedly biased) overview of the pre-transcriptomic history of somatostatin interneuron taxonomy, followed by a chronological summary of the large-scale, NIH-supported effort over the last ten years to generate a comprehensive, single-cell RNA-seq-based taxonomy of cortical neurons. Focusing on somatostatin interneurons, we present the perspective of experimental neuroscientists trying to incorporate the new classification schemes into their own research while struggling to keep up with the ever-increasing number of proposed cell types, which seems to double every two years. We suggest that for experimental analysis, the most useful taxonomic level is the subdivision of somatostatin interneurons into ten or so "supertypes," which closely agrees with their more traditional classification by morphological, electrophysiological and neurochemical features. We argue that finer subdivisions ("t-types" or "clusters"), based on slight variations in gene expression profiles but lacking clear phenotypic differences, are less useful to researchers and may actually defeat the purpose of classifying neurons to begin with. We end by stressing the need for generating novel tools (mouse lines, viral vectors) for genetically targeting distinct supertypes for expression of fluorescent reporters, calcium sensors and excitatory or inhibitory opsins, allowing neuroscientists to chart the input and output synaptic connections of each proposed subtype, reveal the position they occupy in the cortical network and examine experimentally their roles in sensorimotor behaviors and cognitive brain functions. [ABSTRACT FROM AUTHOR]

Background: The failure of amyloid plaque‐reducing drugs to reverse cognitive decline in Alzheimer's disease (AD) has suggested that treatments might be more effective in early or prodromal stages of the disease. However, the progression of synaptic and circuit changes associated with Aβ overexpression, particularly at very early ages, have not been well‐characterized. Indeed, evidence from both human and animal studies indicates that brain structure and function might be altered months to years before plaques can be detected. Method: Here we used quantitative, fluorescence‐based methods for synapse detection in CA1 pyramidal neurons (Pyr) to investigate the interaction between abnormal circuit activity, measured by Fos‐immunoreactivity (Fos‐IR), and synapse reorganization in mouse models of amyloidosis. Result: Using a fluorescently‐tagged molecule (FAPpost) for both excitatory and inhibitory synapses, we find that Aβ overproduction is associated with early synapse gain and loss, depending on the dendritic compartment. Juvenile APP/PS1 and Tg2576 transgenic mice both show a reduction in synapses at the apical tuft of CA1 Pyr and an increase in synapse density along the apical dendrite, which receives inputs from CA3 in animals. These effects were observed at just 6 weeks of age, well before cognitive deficits and amyloid plaques can be detected. Elevated hippocampal activity precedes this reorganization, with elevated Fos‐IR in both CA3 and CA1 present at weaning. Conclusion: These data indicate that elevated Aβ may initiate abnormal activity and subsequently input‐specific synapse plasticity. Taken together, our findings indicate that sustained amyloidosis drives heterogeneous and progressive circuit‐wide abnormalities. [ABSTRACT FROM AUTHOR]

High-throughput anatomic data can stimulate and constrain new hypotheses about how neural circuits change in response to experience. Here, we use fluorescence-based reagents for presynaptic and postsynaptic labeling to monitor changes in thalamocortical synapses onto different compartments of layer 5 (L5) pyramidal (Pyr) neurons in somatosensory (barrel) cortex from mixed-sex mice during whisker-dependent learning (Audette et al., 2019). Using axonal fills and molecular-genetic tags for synapse identification in fixed tissue from Rbp4-Cre transgenic mice, we found that thalamocortical synapses from the higher-order posterior medial thalamic nucleus showed rapid morphologic changes in both presynaptic and postsynaptic structures at the earliest stages of sensory association training. Detected increases in thalamocortical synaptic size were compartment specific, occurring selectively in the proximal dendrites onto L5 Pyr and not at inputs onto their apical tufts in L1. Both axonal and dendritic changes were transient, normalizing back to baseline as animals became expert in the task. Anatomical measurements were corroborated by electrophysiological recordings at different stages of training. Thus, fluorescence-based analysis of input- and target-specific synapses can reveal compartment-specific changes in synapse properties during learning. [ABSTRACT FROM AUTHOR]

Abstract Background Neuronal activity regulates gene expression to control learning and memory, homeostasis of neuronal function, and pathological disease states such as epilepsy. A great deal of experimental evidence supports the involvement of two particular transcription factors in shaping the genomic response to neuronal activity and mediating plasticity: CREB and zif268 (egr-1, krox24, NGFI-A). The gene targets of these two transcription factors are of considerable interest, since they may help develop hypotheses about how neural activity is coupled to changes in neural function. Results We have developed a computational approach for identifying binding sites for these transcription factors within the promoter regions of annotated genes in the mouse, rat, and human genomes. By combining a robust search algorithm to identify discrete binding sites, a comparison of targets across species, and an analysis of binding site locations within promoter regions, we have defined a group of candidate genes that are strong CREB- or zif268 targets and are thus regulated by neural activity. Our analysis revealed that CREB and zif268 share a disproportionate number of targets in common and that these common targets are dominated by transcription factors. Conclusion These observations may enable a more detailed understanding of the regulatory networks that are induced by neural activity and contribute to the plasticity transcriptome. The target genes identified in this study will be a valuable resource for investigators who hope to define the functions of specific genes that underlie activity-dependent changes in neuronal properties.