{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T08:24:30Z","timestamp":1765268670814,"version":"3.37.3"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,9,16]],"date-time":"2020-09-16T00:00:00Z","timestamp":1600214400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,9,16]],"date-time":"2020-09-16T00:00:00Z","timestamp":1600214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG043430-01A1"],"award-info":[{"award-number":["R01AG043430-01A1"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Psychopharmacology"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Rationale<\/jats:title>\n                <jats:p>Metabotropic glutamate type 5 receptor (mGluR5) antagonists are under development for treating cognitive disorders such as Fragile X syndrome and Alzheimer\u2019s disease, largely based on success in mouse models, where post-synaptic mGluR5 stimulation weakens synaptic functions in hippocampus. However, human trials of mGluR5 antagonists have yet to be successful. This may be due in part to the differing effects of mGluR5 in hippocampus vs. prefrontal cortex, as mGluR5 are primarily post-synaptic in rodent hippocampus, but are both pre- and post-synaptic in the dorsolateral prefrontal cortical (dlPFC) circuits known to subserve working memory.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Objectives and methods<\/jats:title>\n                <jats:p>The current study examined the effects of the selective mGluR5 negative allosteric modulator, MTEP (3-((2-Methyl-1,3-thiazol-4-yl)ethynyl)pyridine hydrochloride), on neuronal firing and working memory performance in aging rhesus monkeys with naturally occurring impairments in neuronal firing and cognitive performance.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We found that iontophoresis of MTEP directly onto dlPFC \u201cDelay cells\u201d had an inverted U dose-response, where low doses tended to enhance task-related firing, but higher doses suppressed neuronal firing. Similar effects were seen on cognitive performance following systemic MTEP administration (0.0001\u20130.1 mg\/kg), with MTEP producing erratic dose-response curves. In the subset of monkeys (50%) that showed replicable improvement with MTEP, co-administration with the mGluR5 PAM, CDPPB (3-Cyano-<jats:italic>N<\/jats:italic>-(1,3-diphenyl-1<jats:italic>H<\/jats:italic>-pyrazol-5-yl)benzamide), blocked MTEP beneficial effects, consistent with mGluR5 actions.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The mixed effects of MTEP on cognitive performance may arise from opposing actions at pre- vs. post-synaptic mGluR5 in dlPFC. These data from monkeys suggest that future clinical trials should include low doses, and identification of potential subgroup responders.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00213-020-05661-2","type":"journal-article","created":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T01:18:51Z","timestamp":1600305531000},"page":"97-106","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Effects of blocking mGluR5 on primate dorsolateral prefrontal cortical neuronal firing and working memory performance"],"prefix":"10.1007","volume":"238","author":[{"given":"Sheng-Tao","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronica","family":"Galvin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3420-1308","authenticated-orcid":false,"given":"Amy F. T.","family":"Arnsten","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,9,16]]},"reference":[{"key":"5661_CR1","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1021\/acsptsci.0c00013","volume":"3","author":"KS Abd-Elrahman","year":"2020","unstructured":"Abd-Elrahman KS, Hamilton A, Albaker A, Ferguson SSG (2020) mGluR5 contribution to neuropathology in Alzheimer mice is disease stage-dependent. ACS Pharmacol Transl Sci 3:334\u2013344","journal-title":"ACS Pharmacol Transl Sci"},{"key":"5661_CR2","doi-asserted-by":"publisher","first-page":"4287","DOI":"10.1523\/JNEUROSCI.08-11-04287.1988","volume":"8","author":"AFT Arnsten","year":"1988","unstructured":"Arnsten AFT, Cai JX, Goldman-Rakic PS (1988) The alpha-2 adrenergic agonist guanfacine improves memory in aged monkeys without sedative or hypotensive side effects. J Neurosci 8:4287\u20134298","journal-title":"J Neurosci"},{"key":"5661_CR3","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.neuron.2012.08.038","volume":"76","author":"AFT Arnsten","year":"2012","unstructured":"Arnsten AFT, Wang M, Paspalas CD (2012) Neuromodulation of thought: flexibilities and vulnerabilities in prefrontal cortical network synapses. Neuron 76:223\u2013239","journal-title":"Neuron"},{"key":"5661_CR4","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.tins.2004.04.009","volume":"27","author":"MF Bear","year":"2004","unstructured":"Bear MF, Huber KM, Warren ST (2004) The mGluR theory of fragile X mental retardation. Trends Neurosci 27:370\u2013377","journal-title":"Trends Neurosci"},{"key":"5661_CR5","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1038\/sj.npp.1301610","volume":"33","author":"MF Bear","year":"2008","unstructured":"Bear MF, D\u00f6len G, Osterweil E, Nagarajan N (2008) Fragile X: translation in action. Neuropsychopharmacology 33:84\u201387","journal-title":"Neuropsychopharmacology"},{"key":"5661_CR6","doi-asserted-by":"publisher","first-page":"321ra5","DOI":"10.1126\/scitranslmed.aab4109","volume":"8","author":"E Berry-Kravis","year":"2016","unstructured":"Berry-Kravis E, Des Portes V, Hagerman R, Jacquemont S, Charles P, Visootsak J, Brinkman M, Rerat K, Koumaras B, Zhu L, Barth GM, Jaecklin T, Apostol G, von Raison F (2016) Mavoglurant in fragile X syndrome: results of two randomized, double-blind, placebo-controlled trials. Sci Transl Med 8:321ra5","journal-title":"Sci Transl Med"},{"key":"5661_CR7","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1038\/nrd.2017.221","volume":"17","author":"EM Berry-Kravis","year":"2018","unstructured":"Berry-Kravis EM, Lindemann L, J\u00f8nch AE, Apostol G, Bear MF, Carpenter RL, Crawley JN, Curie A, Des Portes V, Hossain F, Gasparini F, Gomez-Mancilla B, Hessl D, Loth E, Scharf SH, Wang PP, Von Raison F, Hagerman R, Spooren W, Jacquemont S (2018) Drug development for neurodevelopmental disorders: lessons learned from fragile X syndrome. Nat Rev Drug Discov 17:280\u2013299","journal-title":"Nat Rev Drug Discov"},{"key":"5661_CR8","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1007\/s00259-015-3167-6","volume":"43","author":"JM DuBois","year":"2016","unstructured":"DuBois JM, Rousset OG, Rowley J, Porras-Betancourt M, Reader AJ, Labbe A, Massarweh G, Soucy JP, Rosa-Neto P, Kobayashi E (2016) Characterization of age\/sex and the regional distribution of mGluR5 availability in the healthy human brain measured by high-resolution [(11)C]ABP688 PET. Eur J Nucl Med Mol Imaging 43:152\u2013162","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"5661_CR9","doi-asserted-by":"crossref","unstructured":"Fitzgerald ML, Mackie K, Pickel VM (2019) Ultrastructural localization of cannabinoid CB1 and mGluR5 receptors in the prefrontal cortex and amygdala. J Comp Neurol 527, 2730, 2741. April 22: [Epub ahead of print]","DOI":"10.1002\/cne.24704"},{"key":"5661_CR10","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1126\/science.173.3997.652","volume":"173","author":"JM Fuster","year":"1971","unstructured":"Fuster JM, Alexander GE (1971) Neuron activity related to short-term memory. Science 173:652\u2013654","journal-title":"Science"},{"key":"5661_CR11","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/0896-6273(95)90304-6","volume":"14","author":"PS Goldman-Rakic","year":"1995","unstructured":"Goldman-Rakic PS (1995) Cellular basis of working memory. Neuron 14:477\u2013485","journal-title":"Neuron"},{"key":"5661_CR12","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1093\/cercor\/10.1.82","volume":"10","author":"G Gonz\u00e1lez-Burgos","year":"2000","unstructured":"Gonz\u00e1lez-Burgos G, Barrionuevo G, Lewis DA (2000) Horizontal synaptic connections in monkey prefrontal cortex: an in vitro electrophysiological study. Cereb Cortex 10:82\u201392","journal-title":"Cereb Cortex"},{"key":"5661_CR13","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1152\/jn.00787.2004","volume":"93","author":"G Gonz\u00e1lez-Burgos","year":"2005","unstructured":"Gonz\u00e1lez-Burgos G, Krimer LS, Povysheva NV, Barrionuevo G, Lewis DA (2005) Functional properties of fast spiking interneurons and their synaptic connections with pyramidal cells in primate dorsolateral prefrontal cortex. J Neurophysiol 93:942\u2013953","journal-title":"J Neurophysiol"},{"key":"5661_CR14","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.celrep.2017.06.023","volume":"20","author":"LT Haas","year":"2017","unstructured":"Haas LT, Salazar SV, Smith LM, Zhao HR, Cox TO, Herber CS, Degnan AP, Balakrishnan A, Macor JE, Albright CF, Strittmatter SM (2017) Silent allosteric modulation of mGluR5 maintains glutamate signaling while rescuing Alzheimer\u2019s mouse phenotypes. Cell Rep 20:76\u201388","journal-title":"Cell Rep"},{"key":"5661_CR15","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/1756-6606-7-40","volume":"7","author":"A Hamilton","year":"2014","unstructured":"Hamilton A, Esseltine JL, DeVries RA, Cregan SP, Ferguson SS (2014) Metabotropic glutamate receptor 5 knockout reduces cognitive impairment and pathogenesis in a mouse model of Alzheimer's disease. Mol Brain 7:40","journal-title":"Mol Brain"},{"key":"5661_CR16","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s13041-015-0107-0","volume":"8","author":"A Hamilton","year":"2015","unstructured":"Hamilton A, Zamponi GW, Ferguson SS (2015) Glutamate receptors function as scaffolds for the regulation of \u03b2-amyloid and cellular prion protein signaling complexes. Mol Brain 8:18","journal-title":"Mol Brain"},{"key":"5661_CR17","doi-asserted-by":"publisher","unstructured":"Hernandez CM, McQuail JA, Schwabe MR, Burke SN, Setlow B, Bizon JL (2018) Age-related declines in prefrontal cortical expression of metabotropic glutamate receptors that support working memory. eNeuro 5. https:\/\/doi.org\/10.1523\/ENEURO.0164-18.2018","DOI":"10.1523\/ENEURO.0164-18.2018"},{"key":"5661_CR18","doi-asserted-by":"publisher","first-page":"e0209984","DOI":"10.1371\/journal.pone.0209984","volume":"14","author":"D Hessl","year":"2019","unstructured":"Hessl D, Harvey D, Sansone S, Crestodina C, Chin J, Joshi R, Hagerman R, Berry-Kravis E (2019) Effects of mavoglurant on visual attention and pupil reactivity while viewing photographs of faces in Fragile X Syndrome. PLoS One 14:e0209984","journal-title":"PLoS One"},{"key":"5661_CR19","doi-asserted-by":"publisher","first-page":"3374","DOI":"10.1038\/ncomms4374","volume":"5","author":"NW Hu","year":"2014","unstructured":"Hu NW, Nicoll AJ, Zhang D, Mably AJ, O'Malley T, Purro SA, Terry C, Collinge J, Walsh DM, Rowan MJ (2014) mGlu5 receptors and cellular prion protein mediate amyloid-\u03b2-facilitated synaptic long-term depression in vivo. Nat Commun 5:3374","journal-title":"Nat Commun"},{"key":"5661_CR20","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1111\/jnc.14290","volume":"145","author":"SN Isherwood","year":"2018","unstructured":"Isherwood SN, Robbins TW, Dalley JW, Pekcec A (2018) Bidirectional variation in glutamate efflux in the medial prefrontal cortex induced by selective positive and negative allosteric mGluR5 modulators. J Neurochem 145:111\u2013124","journal-title":"J Neurochem"},{"key":"5661_CR21","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1038\/383089a0","volume":"383","author":"S Kawabata","year":"1996","unstructured":"Kawabata S, Tsutsumi R, Kohara A, Yamaguchi T, Nakanishi S, Okada M (1996) Control of calcium oscillations by phosphorylation of metabotropic glutamate receptors. Nature 383:89\u201392","journal-title":"Nature"},{"key":"5661_CR22","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.pscychresns.2006.01.003","volume":"146","author":"SK Keedy","year":"2006","unstructured":"Keedy SK, Ebens CL, Keshavan MS, Sweeney JA (2006) Functional magnetic resonance imaging studies of eye movements in first episode schizophrenia: smooth pursuit, visually guided saccades and the oculomotor delayed response task. Psychiatry Res 146:199\u2013211","journal-title":"Psychiatry Res"},{"key":"5661_CR23","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.neuropharm.2012.03.024","volume":"66","author":"T Kiritoshi","year":"2013","unstructured":"Kiritoshi T, Sun H, Ren W, Stauffer SR, Lindsley CW, Conn PJ, Neugebauer V (2013) Modulation of pyramidal cell output in the medial prefrontal cortex by mGluR5 interacting with CB1. Neuropharmacology 66:170\u2013178","journal-title":"Neuropharmacology"},{"key":"5661_CR24","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1146\/annurev-med-061109-134644","volume":"62","author":"DD Krueger","year":"2011","unstructured":"Krueger DD, Bear MF (2011) Toward fulfilling the promise of molecular medicine in fragile X syndrome. Annu Rev Med 62:411\u2013429","journal-title":"Annu Rev Med"},{"key":"5661_CR25","first-page":"215","volume":"9","author":"A Kumar","year":"2015","unstructured":"Kumar A, Dhull DK, Mishra PS (2015) Therapeutic potential of mGluR5 targeting in Alzheimer\u2019s disease. Front Neurosci 9:215","journal-title":"Front Neurosci"},{"key":"5661_CR26","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1111\/j.1527-3458.2006.00149.x","volume":"12","author":"PM Lea","year":"2006","unstructured":"Lea PM, Faden AI (2006) Metabotropic glutamate receptor subtype 5 antagonists MPEP and MTEP. CNS Drug Rev 12:149\u2013166","journal-title":"CNS Drug Rev"},{"key":"5661_CR27","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1002\/cne.10937","volume":"467","author":"EC Muly","year":"2003","unstructured":"Muly EC, Maddox M, Smith Y (2003) Distribution of mGluR1alpha and mGluR5 immunolabeling in primate prefrontal cortex. J Comp Neurol 467:521\u2013535","journal-title":"J Comp Neurol"},{"key":"5661_CR28","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1146\/annurev.pharmtox.011008.145533","volume":"50","author":"CM Niswender","year":"2010","unstructured":"Niswender CM, Conn PJ (2010) Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annu Rev Pharmacol Toxicol 50:295\u2013322","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"5661_CR29","doi-asserted-by":"publisher","first-page":"4391","DOI":"10.1038\/s41598-018-22768-x","volume":"8","author":"KJ O\u2019Riordan","year":"2018","unstructured":"O\u2019Riordan KJ, Hu NW, Rowan MJ (2018) Physiological activation of mGlu5 receptors supports the ion channel function of NMDA receptors in hippocampal LTD induction in vivo. Sci Rep 8:4391","journal-title":"Sci Rep"},{"key":"5661_CR30","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1016\/j.neulet.2003.12.075","volume":"361","author":"YK Park","year":"2004","unstructured":"Park YK, Galik J, Ryu PD, Randic M (2004) Activation of presynaptic group I metabotropic glutamate receptors enhances glutamate release in the rat spinal cord substantia gelatinosa. Neurosci Lett 361:220\u2013224","journal-title":"Neurosci Lett"},{"key":"5661_CR31","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1177\/0269881114542856","volume":"28","author":"M Pollard","year":"2014","unstructured":"Pollard M, Bartolome JM, Conn PJ, Steckler T, Shaban H (2014) Modulation of neuronal microcircuit activities within the medial prefrontal cortex by mGluR5 positive allosteric modulator. J Psychopharmacol 28:935\u2013946","journal-title":"J Psychopharmacol"},{"key":"5661_CR32","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1016\/j.neuron.2010.04.029","volume":"66","author":"M Renner","year":"2010","unstructured":"Renner M, Lacor PN, Velasco PT, Xu J, Contractor A, Klein WL, Triller A (2010) Deleterious effects of amyloid beta oligomers acting as an extracellular scaffold for mGluR5. Neuron 66:739\u2013754","journal-title":"Neuron"},{"key":"5661_CR33","doi-asserted-by":"publisher","first-page":"7503","DOI":"10.1523\/JNEUROSCI.17-19-07503.1997","volume":"17","author":"R Shigemoto","year":"1997","unstructured":"Shigemoto R, Kinoshita A, Wada E, Nomura S, Ohishi H, Takada M, Flor PJ, Neki A, Abe T, Nakanishi S, Mizuno N (1997) Differential presynaptic localization of metabotropic glutamate receptor subtypes in the rat hippocampus. J Neurosci 17:7503\u20137522","journal-title":"J Neurosci"},{"key":"5661_CR34","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1038\/nn.2245","volume":"12","author":"K Sidiropoulou","year":"2009","unstructured":"Sidiropoulou K, Lu FM, Fowler MA, Xiao R, Phillips C, Ozkan ED, Zhu MX, White FJ, Cooper DC (2009) Dopamine modulates an mGluR5-mediated depolarization underlying prefrontal persistent activity. Nat Neurosci 12:190\u2013199","journal-title":"Nat Neurosci"},{"key":"5661_CR35","doi-asserted-by":"publisher","first-page":"131ra51","DOI":"10.1126\/scitranslmed.3003501","volume":"4","author":"JL Silverman","year":"2012","unstructured":"Silverman JL, Smith DG, Rizzo SJ, Karras MN, Turner SM, Tolu SS, Bryce DK, Smith DL, Fonseca K, Ring RH, Crawley JN (2012) Negative allosteric modulation of the mGluR5 receptor reduces repetitive behaviors and rescues social deficits in mouse models of autism. Sci Transl Med 4:131ra51","journal-title":"Sci Transl Med"},{"key":"5661_CR36","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1212\/WNL.0b013e3182166dc7","volume":"76","author":"DK Sokol","year":"2011","unstructured":"Sokol DK, Maloney B, Long JM, Ray B, Lahiri DK (2011) Autism, Alzheimer disease, and fragile X: APP, FMRP, and mGluR5 are molecular links. Neurology 76:1344\u20131352","journal-title":"Neurology"},{"key":"5661_CR37","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1016\/j.neuron.2013.06.036","volume":"79","author":"JW Um","year":"2013","unstructured":"Um JW, Kaufman AC, Kostylev M, Heiss JK, Stagi M, Takahashi H, Kerrisk ME, Vortmeyer A, Wisniewski T, Koleske AJ, Gunther EC, Nygaard HB, Strittmatter SM (2013) Metabotropic glutamate receptor 5 is a coreceptor for Alzheimer a\u03b2 oligomer bound to cellular prion protein. Neuron 79:887\u2013902","journal-title":"Neuron"},{"key":"5661_CR38","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.cell.2007.03.015","volume":"129","author":"M Wang","year":"2007","unstructured":"Wang M, Ramos B, Paspalas C, Shu Y, Simen A, Duque A, Vijayraghavan S, Brennan A, Dudley AG, Nou E, Mazer JA, McCormick DA, Arnsten AFT (2007) Alpha2A-adrenoceptor stimulation strengthens working memory networks by inhibiting cAMP-HCN channel signaling in prefrontal cortex. Cell 129:397\u2013410","journal-title":"Cell"},{"key":"5661_CR39","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1038\/nature10243","volume":"476","author":"M Wang","year":"2011","unstructured":"Wang M, Gamo NJ, Yang Y, Jin LE, Wang XJ, Laubach M, Mazer JA, Lee D, Arnsten AFT (2011) Neuronal basis of age-related working memory decline. Nature 476:210\u2013213","journal-title":"Nature"},{"key":"5661_CR40","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1016\/j.neuron.2012.12.032","volume":"77","author":"M Wang","year":"2013","unstructured":"Wang M, Yang Y, Wang CJ, Gamo NJ, Jin LE, Mazer JA, Morrison JH, Wang X-J, Arnsten AF (2013) NMDA receptors subserve working memory persistent neuronal firing In dorsolateral prefrontal cortex. Neuron 77:736\u2013749","journal-title":"Neuron"},{"key":"5661_CR41","doi-asserted-by":"publisher","first-page":"e52","DOI":"10.1371\/journal.pbio.0050052","volume":"5","author":"CJ Westmark","year":"2007","unstructured":"Westmark CJ, Malter JS (2007) FMRP mediates mGluR5-dependent translation of amyloid precursor protein. PLoS Biol 5:e52","journal-title":"PLoS Biol"},{"key":"5661_CR42","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1146\/annurev-neuro-080317-061450","volume":"41","author":"MK Wittmann","year":"2018","unstructured":"Wittmann MK, Lockwood PL, Rushworth MFS (2018) Neural mechanisms of social cognition in primates. Annu Rev Neurosci 41:99\u2013118","journal-title":"Annu Rev Neurosci"},{"key":"5661_CR43","doi-asserted-by":"publisher","first-page":"1458","DOI":"10.1093\/cercor\/bhx357","volume":"28","author":"ST Yang","year":"2018","unstructured":"Yang ST, Wang M, Paspalas CP, Crimins JL, Altman MT, Mazer JA, Arnsten AF (2018) Core differences in synaptic signaling between primary visual and dorsolateral prefrontal cortex. Cereb Cortex 28:1458\u20131471","journal-title":"Cereb Cortex"},{"key":"5661_CR44","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1111\/j.1460-9568.2008.06409.x","volume":"28","author":"M Yoshida","year":"2008","unstructured":"Yoshida M, Frans\u00e9n E, Hasselmo ME (2008) mGluR-dependent persistent firing in entorhinal cortex layer III neurons. Eur J Neurosci 28:1116\u20131126","journal-title":"Eur J Neurosci"},{"key":"5661_CR45","doi-asserted-by":"crossref","unstructured":"Zhang Z, S\u00e9gu\u00e9la P (2010) Metabotropic Induction of persistent activity in layers II\/III of anterior cingulate cortex Cerebral Cortex. 20:2948\u20132957","DOI":"10.1093\/cercor\/bhq043"}],"container-title":["Psychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00213-020-05661-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00213-020-05661-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00213-020-05661-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T23:34:47Z","timestamp":1631748887000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00213-020-05661-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,16]]},"references-count":45,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["5661"],"URL":"https:\/\/doi.org\/10.1007\/s00213-020-05661-2","relation":{},"ISSN":["0033-3158","1432-2072"],"issn-type":[{"type":"print","value":"0033-3158"},{"type":"electronic","value":"1432-2072"}],"subject":[],"published":{"date-parts":[[2020,9,16]]},"assertion":[{"value":"3 June 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 September 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 September 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All research was approved by the Yale IACUC and was in accordance with NIH guidelines.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"AFTA and Yale receive royalties from Shire\/Takeda for the USA sales of extended release guanfacine (Intuniv), an alpha-2A-adrenoceptor agonist. They do not receive royalties from non-USA or generic sales. None of the other authors has any conflicts of interest to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}