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Sensory information may be modulated by projections from the brain to the spinal cord, but the neural substrates for top\u2010down sensory control are incompletely understood. We identified a novel population of inhibitory neurons in the mouse brainstem, distinguished by their expression of prodynorphin, which we named LJA5. Here, we identify a similar group of\n                    <jats:italic>Pdyn+<\/jats:italic>\n                    neurons in the human brainstem, and we define the efferent and afferent projection patterns of LJA5 neurons in mouse. Using specific genetic tools, we selectively traced the projections of the\n                    <jats:italic>Pdyn<\/jats:italic>\n                    \u2010expressing LJA5 neurons through the brain and spinal cord. Terminal fields were densest in the lateral and ventrolateral periaqueductal gray (PAG), lateral parabrachial nucleus (LPB), caudal pressor area, and lamina I of the spinal trigeminal nucleus and all levels of the spinal cord. We then labeled cell types in the PAG, LPB, medulla, and spinal cord to better define the specific targets of LJA5 boutons. LJA5 neurons send the only known inhibitory descending projection specifically to lamina I of the spinal cord, which transmits afferent pain, temperature, and itch information up to the brain. Using retrograde tracing, we found LJA5 neurons receive inputs from sensory and stress areas such as somatosensory\/insular cortex, preoptic area, paraventricular nucleus, dorsomedial nucleus and lateral hypothalamus, PAG, and LPB. This pattern of inputs and outputs suggest LJA5 neurons are uniquely positioned to be activated by sensation and stress, and in turn, inhibit pain and itch.\n                  <\/jats:p>","DOI":"10.1002\/cne.24974","type":"journal-article","created":{"date-parts":[[2020,6,30]],"date-time":"2020-06-30T08:03:47Z","timestamp":1593504227000},"page":"635-654","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Input\u2013output connections of\n                    <scp>LJA5<\/scp>\n                    prodynorphin neurons"],"prefix":"10.1002","volume":"529","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8382-6638","authenticated-orcid":false,"given":"Lindsay J.","family":"Agostinelli","sequence":"first","affiliation":[{"name":"Department of Neurology, Roy J. and Lucille A. Carver College of Medicine The University of Iowa  Iowa City Iowa USA"},{"name":"Department of Pediatrics University of Iowa  Iowa City Iowa USA"},{"name":"Department of Neurology Beth Israel Deaconess Medical Center and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madison R.","family":"Mix","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Iowa  Iowa City Iowa USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3127-4528","authenticated-orcid":false,"given":"Marco M.","family":"Hefti","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Iowa  Iowa City Iowa USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas E.","family":"Scammell","sequence":"additional","affiliation":[{"name":"Department of Neurology Beth Israel Deaconess Medical Center and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander G.","family":"Bassuk","sequence":"additional","affiliation":[{"name":"Department of Neurology, Roy J. and Lucille A. Carver College of Medicine The University of Iowa  Iowa City Iowa USA"},{"name":"Department of Pediatrics University of Iowa  Iowa City Iowa USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,7,24]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-018-01820-6"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1251210"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0361-9230(88)90033-0"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.101998"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.10.037"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903530403"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2000.83.4.2239"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.23024"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902610406"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903510408"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25511"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902400205"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(93)90210-E"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903610204"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn894"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2555"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.03.023"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.1989.tb08760.x"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902490302"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ne.14.030191.001251"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1567-424X(09)70068-6"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(92)90192-5"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.11.010"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00094.2015"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2017.05.010"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(88)90693-2"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.05.057"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2003.12.042"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(93)91669-J"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0793-8"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(89)90229-7"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2004.09.010"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1410.012"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(85)91254-5"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.02.046"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-010-1819-6"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12956"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1159\/000341268"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(73)90748-8"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.3109\/08990229309028840"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/265358a0"},{"issue":"6","key":"e_1_2_11_43_1","first-page":"R1156","article-title":"Cardiovascular 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