Journal
BEHAVIOURAL BRAIN RESEARCH
Volume 372, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.bbr.2019.111984
Keywords
BDNF; TrkB; Parvalbumin; Memory; Learning; Hippocampus
Categories
Funding
- NHMRC/ARC [1109959]
- National Health and Medical Research Council [1062826]
- National Health and Medical Research Council of Australia [1109959] Funding Source: NHMRC
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Schizophrenia is a debilitating disorder characterised by three main symptom categories: positive, negative and cognitive. Cognitive symptoms emerge first, and currently do not have appropriate treatments, despite being a strong predictor of the severity and progress of the illness. Cognitive deficits are strongly associated with the dysfunction of GABAergic parvalbumin intemeurons (PV-IN). PV-IN are supported by Brain-Derived Neurotrophic Factor (BDNF) via its receptor Tropomyosin-related Kinase B (TrkB). The main aim of this study was to investigate the cognitive and affective consequences of disrupted BDNF-TrkB signalling at PV-IN. We crossed PV-Cre mice with heterozygous TrkB floxed mice (PV-Cre:Fl(+/-)) to knock-down TrkB receptors on PV-IN. Male and female mice underwent a battery of tests including: Y-Maze, Cheeseboard Maze, Elevated Plus Maze, and Locomotor activity. Co-expression of PV and TrkB in the hippocampus was assessed by fluorescent immunohistochemistry and detailed stereology. Sex-specific spatial memory impairments were found in the Y-Maze. Only male PV-Cre:Fl(+/-) mice showed no preference for the novel arm. Furthermore, there was a male specific genotype difference in memory retrieval in the Cheeseboard Maze. Male PV-Cre:Fl(+/-) mice were more preservative in their learning than male PV-Cre control mice. Overall, the evidence from this study suggests that sex had a developmental influence on this constitutive model. Male spatial memory was altered by the disruption to BDNF-TrkB signalling at PV-IN. This aligns with males showing more severe cognitive dysfunction in schizophrenia.
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