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Hippocampal damage in humans has been linked to amnesia and memory loss, characteristic of Alzheimer's disease and other dementias. Numerous studies indicate that the rodent hippocampus contributes significantly to long\u2010term memory for spatial and nonspatial information. For example, muscimol\u2010induced depression of CA1 neuronal activity in the dorsal hippocampus impairs the encoding, consolidation, and retrieval of nonspatial object memory in mice. Here, a chemogenetic designer receptor exclusively activated by designer drugs (DREADDs) approach was used to test the selective involvement of CA1 pyramidal neurons in memory retrieval for objects and for spatial location in a cohort of male C57BL\/6J mice. Activation of the inhibitory (hM4Di) DREADDs receptor expressed in CA1 neurons significantly impaired the retrieval of object memory in the spontaneous object recognition task and of spatial memory in the Morris water maze. Silencing of CA1 neuronal activity in hM4Di\u2010expressing mice was confirmed by comparing Fos expression in vehicle\u2010 and clozapine\u2010<jats:italic>N<\/jats:italic>\u2010oxide\u2010treated mice after exploration of a novel environment. Histological analyses revealed that expression of the hM4Di receptor was limited to CA1 neurons of the dorsal hippocampus. These results suggest that a common subset of CA1 neurons (i.e., those expressing hM4Di receptors) in mouse hippocampus contributed to the retrieval of long\u2010term memory for nonspatial and spatial information. Our findings support the view that the contribution of the rodent hippocampus is like that of the primate hippocampus, specifically essential for global memory. Our results further validate mice as a suitable model system to study the neurobiological mechanisms of human episodic memory, but also in developing treatments and understanding the underlying causes of diseases affecting long\u2010term memory, such as Alzheimer's disease.<\/jats:p>","DOI":"10.1002\/hipo.23484","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T08:40:39Z","timestamp":1670229639000},"page":"6-17","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["<scp>DREADD<\/scp>\u2010inactivation of dorsal <scp>CA1<\/scp> pyramidal neurons in mice impairs retrieval of object and spatial memories"],"prefix":"10.1002","volume":"33","author":[{"suffix":"Jr.","given":"David A.","family":"Cinalli","sequence":"first","affiliation":[{"name":"Department of Psychology, Charles E. Schmidt College of Science Florida Atlantic University  Boca Raton Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Jupiter Life Science Initiative, John D. MacArthur Campus Florida Atlantic University  Jupiter Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariah","family":"Calubag","sequence":"additional","affiliation":[{"name":"Harriet L. Wilkes Honors College Florida Atlantic University  Jupiter Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goksu","family":"Oz","sequence":"additional","affiliation":[{"name":"Department of Psychology, Charles E. Schmidt College of Science Florida Atlantic University  Boca Raton Florida USA"},{"name":"Florida Atlantic University and Max Planck Florida Institute Joint Integrative Biology \u2010 Neuroscience Ph.D. Program Florida Atlantic University  Jupiter Florida USA"},{"name":"International Max Planck Research School for Synapses and Circuits Florida Atlantic University and Max Planck Florida Institute for Neuroscience  Jupiter Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lylybell","family":"Zhou","sequence":"additional","affiliation":[{"name":"Alexander W. Dreyfoos High School of the Arts  West Palm Beach Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5950-046X","authenticated-orcid":false,"suffix":"Jr.","given":"Robert W.","family":"Stackman","sequence":"additional","affiliation":[{"name":"Department of Psychology, Charles E. 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MacArthur Campus Florida Atlantic University  Jupiter Florida USA"},{"name":"Florida Atlantic University and Max Planck Florida Institute Joint Integrative Biology \u2010 Neuroscience Ph.D. Program Florida Atlantic University  Jupiter Florida USA"},{"name":"International Max Planck Research School for Synapses and Circuits Florida Atlantic University and Max Planck Florida Institute for Neuroscience  Jupiter Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2005.09.005"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0700293104"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00278.2019"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2396(199612)24:4"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2009.06.005"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6413-10.2011"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/1815371"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1101\/lm.1650110"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0406344101"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1101\/lm.6.6.572"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0166-4328(00)00155-8"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.450010323"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2020.527543"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-23-08853.2000"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0915059107"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.23040"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2013.07.002"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2014.08.002"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0741-19.2019"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2006.06.044"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2007.08.001"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/35036213"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3827"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.30.051606.094328"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.20059"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.10154"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan2475"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1101\/lm.1986911"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2004.03.005"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05418-8"},{"issue":"2","key":"e_1_2_8_32_1","first-page":"243","article-title":"Rapid formation of clozapine in Guinea\u2010pigs and man following clozapine\u2010N\u2010oxide administration","volume":"328","author":"Jann M. 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