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One debate revolves around the extent to which the ventral hippocampus contributes to spatial navigation and learning. Here, separate small subtotal lesions of dorsal hippocampus or ventral hippocampus alone (destroying 18.9 and 28.5% of total hippocampal volume, respectively) spared reference memory acquisition in the water maze. By contrast, combining the two subtotal lesions significantly reduced the rate of acquisition across days. This constitutes evidence for synergistic integration between dorsal and ventral hippocampus in mice. Evidence that ventral hippocampus contributes to spatial\/navigation learning also emerged early on during the retention probe test as search preference was reduced in mice with ventral lesions alone or combined lesions. The small ventral lesions also led to anxiolysis in the elevated plus maze and over\u2010generalization of the conditioned freezing response to a neutral context. Similar effects of comparable magnitudes were seen in mice with combined lesions, suggesting that they were largely due to the small ventral damage. By contrast, small dorsal lesions were uniquely associated with a severe spatial working memory deficit in the water maze. Taken together, both dorsal and ventral poles of the hippocampus contribute to efficient spatial navigation in mice: While the integrity of dorsal hippocampus is necessary for spatial working memory, the acquisition and retrieval of spatial reference memory are modulated by the ventral hippocampus. Although the impairments following ventral damage (alone or in combination with dorsal damage) were less substantial, a wider spectrum of spatial learning, including context conditioning, was implicated. Our results encourage the search for integrative mechanism between dorsal and ventral hippocampus in spatial learning. Candidate neural substrates may include dorsoventral longitudinal connections and reciprocal modulation via overlapping polysynaptic networks beyond hippocampus.<\/jats:p>","DOI":"10.1002\/hipo.23207","type":"journal-article","created":{"date-parts":[[2020,4,14]],"date-time":"2020-04-14T07:25:53Z","timestamp":1586849153000},"page":"938-957","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Small lesions of the dorsal or ventral hippocampus subregions are associated with distinct impairments in working memory and reference memory retrieval, and combining them attenuates the acquisition rate of spatial reference memory"],"prefix":"10.1002","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7988-5291","authenticated-orcid":false,"given":"Jonas","family":"Hauser","sequence":"first","affiliation":[{"name":"Laboratory of Behavioural Neurobiology Swiss Federal Institute of Technology Zurich  Schwerzenbach Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9458-8498","authenticated-orcid":false,"given":"Luis H.","family":"Llano L\u00f3pez","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurociencias y Psicolog\u00eda Experimental Instituto de Medicina y Biolog\u00eda Experimental de Cuyo (IMBECU), Facultad de Ciencias M\u00e9dicas, Universidad Nacional de Cuyo  Mendoza Argentina"},{"name":"Servicio de Terapia Intensiva Infantil. Servicio de Recuperaci\u00f3n Cardiovascular Pedi\u00e1trica. Hospital Pedi\u00e1trico Humberto Notti  Mendoza Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joram","family":"Feldon","sequence":"additional","affiliation":[{"name":"Laboratory of Behavioural Neurobiology Swiss Federal Institute of Technology Zurich  Schwerzenbach Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascual A.","family":"Gargiulo","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurociencias y Psicolog\u00eda Experimental Instituto de Medicina y Biolog\u00eda Experimental de Cuyo (IMBECU), Facultad de Ciencias M\u00e9dicas, Universidad Nacional de Cuyo  Mendoza Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3220-9162","authenticated-orcid":false,"given":"Benjamin K.","family":"Yee","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Sciences, Faculty of Health &amp; Social Sciences The Hong Kong Polytechnic University  Hung Hom Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,4,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(89)90424-7"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1037\/0735-7044.116.5.884"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-4328(02)00268-1"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2004.03.004"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1037\/0735-7044.113.6.1170"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1515\/REVNEURO.2007.18.3-4.253"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2011.01.003"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1000089"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0241-y"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0406344101"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2018.05.016"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.12.013"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.20985"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2007.05.002"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.10079"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-4328(01)00451-X"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2004.05.027"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.242693"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00010.2013"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1162\/jocn_a_00436"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.11.031"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(03)00473-7"},{"key":"e_1_2_8_24_1","volume-title":"The mouse brain in stereotaxic coordinates","author":"Franklin K. 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