Dysregulation of Specialized Delay/Interference-Dependent Working Memory Following Loss of Dysbindin-1A in Schizophrenia-Related Phenotypes
2017
Dysbindin-1, a protein that regulates aspects of early and late brain development, has
been implicated in the pathobiology of schizophrenia. As the functional roles of the
three major isoforms of dysbindin-1, (A, B and C) remain unknown, we generated a
novel mutant mouse, dys-1A-/-, with selective loss of dysbindin-1A and investigated
schizophrenia-related phenotypes in both males and females. Loss of dysbindin-1A
resulted in heightened initial exploration and disruption in subsequent habituation to a
novel environment, together with heightened anxiety-related behavior in a stressful
environment. Loss of dysbindin-1A was not associated with disruption of either longterm (olfactory) memory or spontaneous alternation behavior. However, dys-1A-/-
showed enhancement in delay-dependent working memory under high levels of
interference relative to controls, i.e. impairment in sensitivity to the disruptive effect
of such interference. These findings in dys-1A-/- provide the first evidence for
differential functional roles for dysbindin-1A vs dysbindin-1C isoforms among
phenotypes relevant to the pathobiology of schizophrenia. Future studies should
investigate putative sex differences in these phenotypic effects.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
86
References
15
Citations
NaN
KQI