{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T06:37:52Z","timestamp":1790491072776,"version":"4.1.0"},"reference-count":65,"publisher":"National Academy of Sciences","issue":"29","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,7,16]]},"abstract":"<jats:p>\n                    The cognitive function of the highly evolved dorsolateral prefrontal cortex (dlPFC) is greatly influenced by arousal state, and is gravely afflicted in disorders such as schizophrenia, where there are genetic insults in \u03b17 nicotinic acetylcholine receptors (\u03b17-nAChRs). A recent behavioral study indicates that ACh depletion from dlPFC markedly impairs working memory [Croxson PL, Kyriazis DA, Baxter MG (2011)\n                    <jats:italic>Nat Neurosci<\/jats:italic>\n                    14(12):1510\u20131512]; however, little is known about how \u03b17-nAChRs influence dlPFC cognitive circuits. Goldman-Rakic [Goldman-Rakic (1995)\n                    <jats:italic>Neuron<\/jats:italic>\n                    14(3):477\u2013485] discovered the circuit basis for working memory, whereby dlPFC pyramidal cells excite each other through glutamatergic NMDA receptor synapses to generate persistent network firing in the absence of sensory stimulation. Here we explore \u03b17-nAChR localization and actions in primate dlPFC and find that they are enriched in glutamate network synapses, where they are essential for dlPFC persistent firing, with permissive effects on NMDA receptor actions. Blockade of \u03b17-nAChRs markedly reduced, whereas low-dose stimulation selectively enhanced, neuronal representations of visual space. These findings in dlPFC contrast with the primary visual cortex, where nAChR blockade had no effect on neuronal firing [Herrero JL, et al. (2008)\n                    <jats:italic>Nature<\/jats:italic>\n                    454(7208):1110\u20131114]. We additionally show that \u03b17-nAChR stimulation is needed for NMDA actions, suggesting that it is key for the engagement of dlPFC circuits. As ACh is released in cortex during waking but not during deep sleep, these findings may explain how ACh shapes differing mental states during wakefulness vs. sleep. The results also explain why genetic insults to \u03b17-nAChR would profoundly disrupt cognitive experience in patients with schizophrenia.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1307849110","type":"journal-article","created":{"date-parts":[[2013,7,2]],"date-time":"2013-07-02T00:42:22Z","timestamp":1372725742000},"page":"12078-12083","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":183,"title":["Nicotinic \u03b17 receptors enhance NMDA cognitive circuits in dorsolateral prefrontal cortex"],"prefix":"10.1073","volume":"110","author":[{"given":"Yang","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06520; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantinos D.","family":"Paspalas","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06520; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu E.","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06520; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina R.","family":"Picciotto","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06508"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy F. T.","family":"Arnsten","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06520; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06520; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2013,7]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0959-4388(92)90130-D"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.20.1.185"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(03)45013-9"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1417.021"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.09.012"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(98)01361-7"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07141"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2971"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90304-6"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-373644-4.00002-5"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/9.3.213"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1998.79.6.2919"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.12.032"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/ar.a.20278"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(98)00281-9"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.57.1.65"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10760"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7742(06)78008-4"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.2174\/138161210790361434"},{"key":"e_1_3_3_20_2","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1111\/j.1601-183X.2007.00323.x","article-title":"Novel alpha7 nicotinic receptor isoforms and deficient cholinergic transcription in schizophrenia","volume":"7","author":"Severance EG","year":"2008","unstructured":"EG Severance, RH Yolken, Novel alpha7 nicotinic receptor isoforms and deficient cholinergic transcription in schizophrenia. Genes Brain Behav 7, 37\u201345 (2008).","journal-title":"Genes Brain Behav"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm253"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-009-9233-4"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1097\/WNF.0b013e31823a1247"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2011.11060822"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2011.06.039"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2009.06.102"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2012.05.003"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2010.08.006"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pscychresns.2006.09.005"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.2174\/138945012800398937"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2006.03.008"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0027014"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2008.07071135"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(03)03532-7"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5712-09.2010"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1385\/JMN:30:1:149"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/syn.20693"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.03.006"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2009.01.007"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.10659"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3600-11.2011"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1207079"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhr390"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2012.52"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(95)90046-2"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-12-05001.2002"},{"key":"e_1_3_3_47_2","first-page":"159","article-title":"The cholinergic nucleus basalis: A key structure in neocortical arousal","volume":"57","author":"Buzs\u00e0ki G","year":"1989","unstructured":"G Buzs\u00e0ki, FH Gage, The cholinergic nucleus basalis: A key structure in neocortical arousal. EXS 57, 159\u2013171 (1989).","journal-title":"EXS"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2010.104"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1364-6613(02)01992-7"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.08.038"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/34413"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2011.11.015"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.158.7.1105"},{"key":"e_1_3_3_54_2","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1176\/ajp.156.12.1986","article-title":"Rostral and orbital prefrontal cortex dysfunction in the manic state of bipolar disorder","volume":"156","author":"Blumberg HP","year":"1999","unstructured":"HP Blumberg, et al., Rostral and orbital prefrontal cortex dysfunction in the manic state of bipolar disorder. Am J Psychiatry 156, 1986\u20131988 (1999).","journal-title":"Am J Psychiatry"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.162.6.1067"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0025322"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2006.03.054"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2003.10.043"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1097\/YPG.0b013e32833a9b7a"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr357"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1503"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1177\/0269881106060193"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2010.09.004"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhs152"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaac.2010.06.015"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1307849110","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T11:54:57Z","timestamp":1715601297000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1307849110"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,7]]},"references-count":65,"journal-issue":{"issue":"29","published-print":{"date-parts":[[2013,7,16]]}},"alternative-id":["10.1073\/pnas.1307849110"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1307849110","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,7]]},"assertion":[{"value":"2013-07-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}