Doublecortin knockout mice show normal hippocampal-dependent memory despite CA3 lamination defects.

Area of Science:

• Neuroscience
• Genetics
• Developmental Biology

Background:

• Mutations in the X-linked doublecortin gene (DCX) cause severe intellectual disability and epilepsy due to neocortical disorganization.
• Dcx knockout (KO) mice display hippocampal CA3 region lamination defects and interneuron abnormalities, but normal isocortical development.

Purpose of the Study:

• To investigate the neurocognitive profile of Dcx-KO mice, focusing on hippocampal and CA3-dependent functions.
• To assess the impact of CA3 region disorganization on learning and memory in Dcx-KO mice.
• To examine adult hippocampal neurogenesis and behavioral phenotypes in Dcx-KO mice.

Main Methods:

• Utilized a battery of hippocampus-related cognitive tests, including the Barnes maze, contextual fear conditioning, paired associate learning, and object recognition.
• Assessed adult hippocampal neurogenesis by examining granule cell proliferation, survival, and differentiation.
• Evaluated social interaction, aggressive behaviors, and behavioral lateralization following social deprivation.

Main Results:

• Dcx-KO adult males demonstrated preserved performance on hippocampal- and CA3-dependent cognitive tasks.
• Adult hippocampal neurogenesis, including proliferation, survival, and differentiation, was also preserved in Dcx-KO mice.
• Dcx-KO mice exhibited impaired social interaction, reduced aggressive behaviors, and decreased behavioral lateralization after social deprivation.

Conclusions:

• Dcx-KO mice serve as a valuable model for studying the cognitive consequences of hippocampal CA3 disorganization.
• The findings highlight preserved hippocampal-dependent learning and memory despite anatomical abnormalities.
• The study reinforces the association between mouse models of intellectual disability and neuropsychiatric behavioral impairments, particularly concerning social behavior and lateralization.