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      Apparatus design and behavioural testing protocol for the evaluation of spatial working memory in mice through the spontaneous alternation T-maze

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          Abstract

          Spatial working memory can be assessed in mice through the spontaneous alternation T-maze test. The T-maze is a T-shaped apparatus featuring a stem (start arm) and two lateral goal arms (left and right arms). The procedure is based on the natural tendency of rodents to prefer exploring a novel arm over a familiar one, which induces them to alternate the choice of the goal arm across repeated trials. During the task, in order to successfully alternate choices across trials, an animal has to remember which arm had been visited in the previous trial, which makes spontaneous alternation T-maze an optimal test for spatial working memory. As this test relies on a spontaneous behaviour and does not require rewards, punishments or pre-training, it represents a particularly useful tool for cognitive evaluation, both time-saving and animal-friendly. We describe here in detail the apparatus and the protocol, providing representative results on wild-type healthy mice.

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          Place navigation impaired in rats with hippocampal lesions

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            Behavioural and neurochemical effects of post-weaning social isolation in rodents-relevance to developmental neuropsychiatric disorders.

            Exposing mammals to early-life adverse events, including maternal separation or social isolation, profoundly affects brain development and adult behaviour and may contribute to the occurrence of psychiatric disorders, such as depression and schizophrenia in genetically predisposed humans. The molecular mechanisms underlying these environmentally induced developmental adaptations are unclear and best evaluated in animal paradigms with translational salience. Rearing rat pups from weaning in isolation, to prevent social contact with conspecifics, produces reproducible, long-term changes including; neophobia, impaired sensorimotor gating, aggression, cognitive rigidity, reduced prefrontal cortical volume and decreased cortical and hippocampal synaptic plasticity. These alterations are associated with hyperfunction of mesolimbic dopaminergic systems, enhanced presynaptic dopamine (DA) and serotonergic (5-HT) function in the nucleus accumbens (NAcc), hypofunction of mesocortical DA and attenuated 5-HT function in the prefrontal cortex and hippocampus. These behavioural, morphological and neurochemical abnormalities, as reviewed herein, strongly resemble core features of schizophrenia. Therefore unravelling the mechanisms that trigger these sequelae will improve our knowledge of the aetiology of neurodevelopmental psychiatric disorders, enable identification of longitudinal biomarkers of dysfunction and permit predictive screening for novel compounds with potential antipsychotic efficacy.
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              T-maze alternation in the rodent.

              This protocol details a method for using a T-maze to assess the cognitive ability of rodents. The T-maze is an elevated or enclosed apparatus in the form of a T placed horizontally. Animals are started from the base of the T and allowed to choose one of the goal arms abutting the other end of the stem. If two trials are given in quick succession, on the second trial the rodent tends to choose the arm not visited before, reflecting memory of the first choice. This is called 'spontaneous alternation'. This tendency can be reinforced by making the animal hungry and rewarding it with a preferred food if it alternates. Both spontaneous and rewarded alternation are very sensitive to dysfunction of the hippocampus, but other brain structures are also involved. Each trial should be completed in under 2 min, but the total number of trials required will vary according to statistical and scientific requirements.
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                Author and article information

                Contributors
                leocani.letizia@hsr.it
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                27 October 2021
                27 October 2021
                2021
                : 11
                : 21177
                Affiliations
                [1 ]GRID grid.18887.3e, ISNI 0000000417581884, Experimental Neurophysiology Unit, Institute of Experimental Neurology (INSPE), San Raffaele Scientific Institute, , IRCCS-San Raffaele Hospital, ; Milan, Italy
                [2 ]GRID grid.15496.3f, ISNI 0000 0001 0439 0892, Vita-Salute San Raffaele University, ; Milan, Italy
                [3 ]Casa di Cura del Policlinico, Milan, Italy
                Author information
                http://orcid.org/0000-0001-6114-6351
                http://orcid.org/0000-0002-6989-1054
                http://orcid.org/0000-0001-9326-6753
                Article
                402
                10.1038/s41598-021-00402-7
                8551159
                34707108
                7d29bde7-839c-4166-a022-4cdfc499accb
                © The Author(s) 2021

                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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 8 June 2021
                : 11 October 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100007366, Fondazione Italiana Sclerosi Multipla;
                Award ID: Research fellowship n°Cod. 2018/B/3
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100009882, Regione Lombardia;
                Award ID: NeOn project (ID: 239047)
                Funded by: Italian Ministry of Education, University and Research
                Award ID: IVASCOMAR Project (CTN01_00177_165430)
                Categories
                Article
                Custom metadata
                © The Author(s) 2021

                Uncategorized
                working memory,learning and memory,spatial memory,neuroscience
                Uncategorized
                working memory, learning and memory, spatial memory, neuroscience

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