eprintid: 10055126 rev_number: 18 eprint_status: archive userid: 608 dir: disk0/10/05/51/26 datestamp: 2018-09-04 12:08:36 lastmod: 2021-10-06 22:49:28 status_changed: 2018-09-04 12:08:36 type: article metadata_visibility: show creators_name: Wolff, AR creators_name: Bygrave, AM creators_name: Sanderson, DJ creators_name: Boyden, ES creators_name: Bannerman, DM creators_name: Kullmann, DM creators_name: Kätzel, D title: Optogenetic induction of the schizophrenia-related endophenotype of ventral hippocampal hyperactivity causes rodent correlates of positive and cognitive symptoms ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: F81 note: © The Author(s) 2018. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. abstract: Pathological over-activity of the CA1 subfield of the human anterior hippocampus has been identified as a potential predictive marker for transition from a prodromal state to overt schizophrenia. Psychosis, in turn, is associated with elevated activity in the anterior subiculum, the hippocampal output stage directly activated by CA1. Over-activity in these subfields may represent a useful endophenotype to guide translationally predictive preclinical models. To recreate this endophenotype and study its causal relation to deficits in the positive and cognitive symptom domains, we optogenetically activated excitatory neurons of the ventral hippocampus (vHPC; analogous to the human anterior hippocampus), targeting the ventral subiculum. Consistent with previous studies, we found that vHPC over-activity evokes hyperlocomotion, a rodent correlate of positive symptoms. vHPC activation also impaired performance on the spatial novelty preference (SNP) test of short-term memory, regardless of whether stimulation was applied during the encoding or retrieval stage of the task. Increasing dopamine transmission with amphetamine produced hyperlocomotion, but was not associated with SNP impairments. This suggests that short-term memory impairments resulting from hippocampal over-activity likely arise independently of a hyperdopaminergic state, a finding that is consistent with the pharmaco-resistance of cognitive symptoms in patients. date: 2018 date_type: published official_url: https://doi.org/10.1038/s41598-018-31163-5 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green article_type_text: Journal Article verified: verified_manual elements_id: 1578992 doi: 10.1038/s41598-018-31163-5 pii: 10.1038/s41598-018-31163-5 lyricists_name: Kullmann, Dimitri lyricists_id: DMKUL63 actors_name: Bracey, Alan actors_id: ABBRA90 actors_role: owner full_text_status: public publication: Scientific Reports volume: 8 article_number: 12871 event_location: England issn: 2045-2322 citation: Wolff, AR; Bygrave, AM; Sanderson, DJ; Boyden, ES; Bannerman, DM; Kullmann, DM; Kätzel, D; (2018) Optogenetic induction of the schizophrenia-related endophenotype of ventral hippocampal hyperactivity causes rodent correlates of positive and cognitive symptoms. Scientific Reports , 8 , Article 12871. 10.1038/s41598-018-31163-5 <https://doi.org/10.1038/s41598-018-31163-5>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10055126/1/s41598-018-31163-5.pdf