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Ethologically based behavioural and neurochemical characterisation of mice with isoform-specific loss of dysbindin-1A in the context of schizophrenia

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posted on 05.08.2021, 08:48 by Colm MP O'Tuathaigh, Lieve Desbonnet, Christina Payne, Emilie Petit, Rachel Cox, Samim Loftus, Gerard Clarke, John F Cryan, Orna TigheOrna Tighe, Steve Wilson, Brian KirbyBrian Kirby, Timothy G Dinan, John WaddingtonJohn Waddington
Dysbindin-1 is implicated in several aspects of schizophrenia, including cognition and both glutamatergic and dopaminergic neurotransmission. Targeted knockout of dysbindin-1A (Dys-1A KO), the most abundant and widely expressed isoform in the brain, is associated with deficits in delay/interference-dependent working memory. Using an ethologically based approach, the following behavioural phenotypes were examined in Dys-1A KO mice: exploratory activity, social interaction, anxiety and problem-solving ability. Levels of monoamines and their metabolites were measured in striatum, hippocampus and prefrontal cortex using high-performance liquid chromatography with electrochemical detection. The ethogram of initial exploration in Dys-1A KO mice was characterised by increased rearing from a seated position; over subsequent habituation, stillness was decreased relative to wildtype. In a test of dyadic social interaction with an unfamiliar conspecific in a novel environment, female KO mice showed an increase in investigative social behaviours. Marble burying behaviour was unchanged. Using the puzzle-box test to measure general problem-solving performance, no effect of genotype was observed across nine trials of increasing complexity. Dys-1A KO demonstrated lower levels of 5-HT in ratio to its metabolite 5-HIAA in the prefrontal cortex. These studies elaborate the behavioural and neurochemical phenotype of Dys-1A KO mice, revealing subtle genotype-related differences in non-social and social exploratory behaviours and habituation of exploration in a novel environment, as well as changes in 5-HT activity in brain areas related to schizophrenia.

Funding

Science Foundation Ireland (SFI) Principal Investigator grant 07/IN.1/B960

Health Research Board of Ireland Postdoctoral Fellowship PD/2007/20

Irish Government’s National Development Plan

SFI (grant numbers SFI/12/RC/2273, 02/ CE/B124 and 07/CE/B1368)

Health Research Board (HRB) through Health Research Awards (grant no HRA_POR/2011/23, HRA_POR/2012/32 and HRA-POR-2014-647)

History

Comments

The original article is available at https://www.sciencedirect.com

Published Citation

O'Tuathaigh CMP et al. Ethologically based behavioural and neurochemical characterisation of mice with isoform-specific loss of dysbindin-1A in the context of schizophrenia. Neurosci Lett. 2020;736:135218

Publication Date

29 June 2020

PubMed ID

32615248

Department/Unit

  • School of Pharmacy and Biomolecular Sciences

Research Area

  • Health Professions Education
  • Neurological and Psychiatric Disorders

Publisher

Elsevier

Version

  • Published Version (Version of Record)