An adaptive stress response involves various mediators and circuits orchestrating a complex interplay of physiological, emotional, and behavioral adjustments. We identified a population of corticotropin-releasing hormone (CRH) neurons in the lateral part of the interstitial nucleus of the anterior commissure (IPACL), a subdivision of the extended amygdala, which exclusively innervate the substantia nigra (SN). Specific stimulation of this circuit elicits hyperactivation of the hypothalamic-pituitary-adrenal axis, locomotor activation, and avoidance behavior contingent on CRH receptor type 1 (CRHR1) located at axon terminals in the SN, which originate from external globus pallidus (GPe) neurons.
View Article and Find Full Text PDFCD4 T cells are central mediators of adaptive and innate immune responses and constitute a major reservoir for human immunodeficiency virus (HIV) in vivo. Detailed investigations of resting human CD4 T cells have been precluded by the absence of efficient approaches for genetic manipulation limiting our understanding of HIV replication and restricting efforts to find a cure. Here we report a method for rapid, efficient, activation-neutral gene editing of resting, polyclonal human CD4 T cells using optimized cell cultivation and nucleofection conditions of Cas9-guide RNA ribonucleoprotein complexes.
View Article and Find Full Text PDFLyssaviruses are neurotropic rhabdoviruses thought to be restricted to mammalian hosts, and to originate from bats. The identification of lyssavirus sequences from amphibians and reptiles by metatranscriptomics thus comes as a surprise and challenges the mammalian origin of lyssaviruses. The novel sequences of the proposed American tree frog lyssavirus (ATFLV) and anole lizard lyssavirus (ALLV) reveal substantial phylogenetic distances from each other and from bat lyssaviruses, with ATFLV being the most distant.
View Article and Find Full Text PDFThe lateral hypothalamus (LH) is critically involved in the regulation of homeostatic energy balance. Some neurons in the LH express receptors for leptin (LepRb), a hormone known to increase energy expenditure and decrease energy intake. However, the neuroanatomical inputs to LepRb-expressing LH neurons remain unknown.
View Article and Find Full Text PDFVaccines of outstanding efficiency, safety, and public acceptance are needed to halt the current SARS-CoV-2 pandemic. Concerns include potential side effects caused by the antigen itself and safety of viral DNA and RNA delivery vectors. The large SARS-CoV-2 spike (S) protein is the main target of current COVID-19 vaccine candidates but can induce non-neutralizing antibodies, which might cause vaccination-induced complications or enhancement of COVID-19 disease.
View Article and Find Full Text PDFThe insular cortex (IC) plays key roles in emotional and regulatory brain functions and is affected across psychiatric diseases. However, the brain-wide connections of the mouse IC have not been comprehensively mapped. Here, we traced the whole-brain inputs and outputs of the mouse IC across its rostro-caudal extent.
View Article and Find Full Text PDFRhabdoviruses, as single-stranded, negative-sense RNA viruses within the order , are characterised by bullet-shaped or bacteroid particles that contain a helical ribonucleoprotein complex (RNP). Here, we review the components of the RNP and its higher-order structural assembly.
View Article and Find Full Text PDFAnatomically incomplete spinal cord injuries can be followed by functional recovery mediated, in part, by the formation of intraspinal detour circuits. Here, we show that adult mice recover tactile and proprioceptive function following a unilateral dorsal column lesion. We therefore investigated the basis of this recovery and focused on the plasticity of the dorsal column-medial lemniscus pathway.
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