Differential impacts on multiple forms of spatial and contextual memory in diazepam binding inhibitor knockout mice

Ammar L. Ujjainwala, Connor D. Courtney, Natalia M. Wojnowski, Justin S Rhodes, Catherine Christian

Research output: Contribution to journalArticle

Abstract

Learning and memory are fundamental processes that are disrupted in many neurological disorders including Alzheimer’s disease and epilepsy. The hippocampus plays an integral role in these functions, and modulation of synaptic transmission mediated by γ-aminobutyric acid (GABA) type-A receptors (GABA A Rs) impacts hippocampus-dependent learning and memory. The protein diazepam binding inhibitor (DBI) differentially modulates GABA A Rs in various brain regions, including hippocampus, and changes in DBI levels may be linked to altered learning and memory. The effects of genetic loss of DBI signaling on these processes, however, have not been determined. In these studies, we examined male and female constitutive DBI knockout mice and wild-type littermates to investigate the role of DBI signaling in modulating multiple forms of hippocampus-dependent spatial learning and memory. DBI knockout mice did not show impaired discrimination of objects in familiar and novel locations in an object location memory test, but did exhibit reduced time spent exploring the objects. Multiple parameters of Barnes maze performance, testing the capability to utilize spatial reference cues, were disrupted in DBI knockout mice. Furthermore, whereas most wild-type mice adopted a direct search strategy upon learning the location of the target hole, knockout mice showed higher rates of using an inefficient random strategy. In addition, DBI knockout mice displayed typical levels of contextual fear conditioning, but lacked a sex difference observed in wild-type mice. Together, these data suggest that DBI selectively influences certain forms of spatial learning and memory, indicating novel roles for DBI signaling in modulating hippocampus-dependent behavior in a task-specific manner.

Original languageEnglish (US)
Pages (from-to)683-697
Number of pages15
JournalJournal of Neuroscience Research
Volume97
Issue number6
DOIs
StatePublished - Jun 1 2019

Fingerprint

Diazepam Binding Inhibitor
Knockout Mice
Hippocampus
Learning
GABA-A Receptors
Spatial Memory
Aminobutyrates
Nervous System Diseases
Protein Binding
Synaptic Transmission
Sex Characteristics
Fear
Cues
Epilepsy
Alzheimer Disease

Keywords

  • Barnes maze
  • contextual fear conditioning
  • diazepam binding inhibitor
  • hippocampus
  • knockout mouse
  • object location memory
  • sex differences

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Differential impacts on multiple forms of spatial and contextual memory in diazepam binding inhibitor knockout mice. / Ujjainwala, Ammar L.; Courtney, Connor D.; Wojnowski, Natalia M.; Rhodes, Justin S; Christian, Catherine.

In: Journal of Neuroscience Research, Vol. 97, No. 6, 01.06.2019, p. 683-697.

Research output: Contribution to journalArticle

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