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Viral manipulation of functionally distinct interneurons in mice, non-human primates and humans.

ABSTRACT: Recent success in identifying gene-regulatory elements in the context of recombinant adeno-associated virus vectors has enabled cell-type-restricted gene expression. However, within the cerebral cortex these tools are largely limited to broad classes of neurons. To overcome this limitation, we developed a strategy that led to the identification of multiple new enhancers to target functionally distinct neuronal subtypes. By investigating the regulatory landscape of the disease gene Scn1a, we discovered enhancers selective for parvalbumin (PV) and vasoactive intestinal peptide-expressing interneurons. Demonstrating the functional utility of these elements, we show that the PV-specific enhancer allowed for the selective targeting and manipulation of these neurons across vertebrate species, including humans. Finally, we demonstrate that our selection method is generalizable and characterizes additional PV-specific enhancers with exquisite specificity within distinct brain regions. Altogether, these viral tools can be used for cell-type-specific circuit manipulation and hold considerable promise for use in therapeutic interventions.

SUBMITTER: Vormstein-Schneider D

PROVIDER: S-EPMC8015416 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Viral manipulation of functionally distinct interneurons in mice, non-human primates and humans.

Vormstein-Schneider Douglas D Lin Jessica D JD Pelkey Kenneth A KA Chittajallu Ramesh R Guo Baolin B Arias-Garcia Mario A MA Allaway Kathryn K Sakopoulos Sofia S Schneider Gates G Stevenson Olivia O Vergara Josselyn J Sharma Jitendra J Zhang Qiangge Q Franken Tom P TP Smith Jared J Ibrahim Leena A LA Mastro Kevin J KJ Sabri Ehsan E Huang Shuhan S Favuzzi Emilia E Burbridge Timothy T Xu Qing Q Guo Lihua L Vogel Ian I Sanchez Vanessa V Saldi Giuseppe A GA Gorissen Bram L BL Yuan Xiaoqing X Zaghloul Kareem A KA Devinsky Orrin O Sabatini Bernardo L BL Batista-Brito Renata R Reynolds John J Feng Guoping G Fu Zhanyan Z McBain Chris J CJ Fishell Gord G Dimidschstein Jordane J

Nature neuroscience 20200817 12

Recent success in identifying gene-regulatory elements in the context of recombinant adeno-associated virus vectors has enabled cell-type-restricted gene expression. However, within the cerebral cortex these tools are largely limited to broad classes of neurons. To overcome this limitation, we developed a strategy that led to the identification of multiple new enhancers to target functionally distinct neuronal subtypes. By investigating the regulatory landscape of the disease gene Scn1a, we disc ...[more]

PMID: 32807948

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Project description:Different protozoa and metazoa have been detected in great apes, monkeys and humans with possible interspecies exchanges. Some are either nonpathogenic or their detrimental effects on the host are not yet known. Others lead to serious diseases that can even be fatal. Their survey remains of great importance for public health and animal conservation. Fecal samples from gorillas (Gorilla gorilla) and humans living in same area in the Republic of Congo, chimpanzees (Pan troglodytes) from Senegal and one other from the Republic of Congo, Guinea baboons (Papio papio) from Senegal, hamadryas baboons (Papio hamadryas) from Djibouti and Barbary macaques (Macaca sylvanus) from Algeria, were collected. DNA was extracted and screened using specific qPCR assays for the presence of a large number of helminths and protozoa. Positive samples were then amplified in standard PCRs and sequenced when possible. Overall, infection rate was 36.5% in all non-human primates (NHPs) and 31.6% in humans. Great apes were more often infected (63.6%) than monkeys (7.3%). At least twelve parasite species, including ten nematodes and two protozoa were discovered in NHPs and five species, including four nematodes and a protozoan in humans. The prevalences of Giarida lamblia, Necator americanus, Enterobius vermicularis, Strongyloides stercoralis were similar between gorillas and human community co-habiting the same forest ecosystem in the Republic of Congo. In addition, human specific Mansonella perstans (5.1%) and other Mansonella spp. (5.1%) detected in these gorillas suggest a possible cross-species exchange. Low prevalence (2%) of Ascaris lumbricoides, Enterobius vermicularis, Strongyloides stercoralis were observed in chimpanzees, as well as a high prevalence of Abbreviata caucasica (57.1%), which should be considered carefully as this parasite can affect other NHPs, animals and humans. The Barbary macaques were less infected (7.2%) and Oesophagostomum muntiacum was the main parasite detected (5.8%). Finally, we report the presence of Pelodera sp. and an environmental Nematoda DNAs in chimpanzee feces, Nematoda sp. and Bodo sp. in gorillas, as well as DNA of uncharacterized Nematoda in apes and humans, but with a relatively lower prevalence in humans. Prevalence of extraintestinal parasites remains underestimated since feces are not the suitable sampling methods. Using non-invasive sampling (feces) we provide important information on helminths and protozoa that can infect African NHPs and human communities living around them. Public health and animal conservation authorities need to be aware of these infections, as parasites detected in African NHPs could affect both human and other animals' health.

Dataset Information

Viral manipulation of functionally distinct interneurons in mice, non-human primates and humans.

Publications

Viral manipulation of functionally distinct interneurons in mice, non-human primates and humans.

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