Executive functions in agenesis of the corpus callosum: Working memory and sustained attention in the BTBR inbred mouse strain

Abstract

Introduction Agenesis of the corpus callosum (AgCC) is characterized by the congenital partial or complete absence of the corpus callosum. Several strains of mice have been reported to carry AgCC, with the BTBR T+Itpr3tf/J (BTBR) inbred mouse strain consistently showing a complete absence of the corpus callosum, as well as a variable reduction in the size of the hippocampal commissure. While much research has focused on the social deficits of the BTBR strain, little research on its cognitive behavior has been conducted. The goal of our study was to compare two facets of executive functioning, spatial working memory, and sustained attention between the BTBR and C57BL/6J (B6) strains. Methods Spatial working memory was measured utilizing a delayed matching‐to‐position (DMTP) task and sustained attention was measured utilizing an operant task in which mice were trained to distinguish signal and nonsignal events. Results Both the BTBR and B6 mice demonstrated a predictable decline in performance on the DMTP task as the delay interval increased and predictable increase in performance on the sustained attention task as the duration of the signal event increased. Although no significant differences were found between strains on the performance of these tasks, there was a significant difference in learning the association between lever pressing and food reward. Histological investigation confirmed the complete absence of commissural fibers from the corpus callosum, but also the hippocampal commissure, counter to a previous study. Conclusion The results suggest spatial working memory and sustained attention are unaffected by the absence of these commissural fibers alone.

Disconnection between Rat’s Left and Right Hemisphere Impairs Short-Term Memory but Not Long-Term Memory

“…For these reasons, physically cutting only the HC is nearly impossible in rats. One alternative would be to use a species that is genetically deficient in the commissural fibers, such as the BTBR mice [24,25]. However, this approach might be inappropriate because it does not exclude the possibility of compensation by other brain regions or neural circuits, and it would need to be performed in wild-type animals.…”

Brain-Derived Neurotrophic Factor (BDNF) in Mechanisms of Autistic-like Behavior in BTBR Mice: Crosstalk with the Dopaminergic Brain System

“…Thus, our findings are in good concordance with evidence of anxiolytic-like properties of BDNF, including results obtained in animals with an autistic-like phenotype. It could be suggested that the local increase in BDNF expression in the hippocampus partially corrects neuronal deficit in the corpus callosum observed both in ASD patients [95] and BTBR mice [94] that results in the amelioration of anxiety and stereotypical behavior.…”

“…It is known that ASD is characterized by an increase in brain volume due an abnormal cortical overgrowth pattern and by increases in size, spine density, and neuron population that leads to the dysregulation of postnatal synaptic pruning and results in a huge variety of forms and degrees of signal-over-noise discrimination losses [87]. On the other hand, BTBR mice also demonstrate a similar spectrum of neuromorphological abnormalities [88][89][90][91][92][93] including the absence of corpus callosum [94], known for ASD patients [95]. Thus, we can hypothesize that a BDNF-induced increase in neurogenesis and axonal growth may exert diverse effects on autistic-like behavior.…”

Insights into the structure and function of the hippocampus: implications for the pathophysiology and treatment of autism spectrum disorder

“…In addition to the core symptoms of ASD, BTBR mice also display learning and memory impairments in various settings (240)(241)(242). Several histological observations and MRI assessments support separated hippocampal commissure and increased hippocampal volume in BTBR mice relative to controls, and these anatomical changes may underlie their behavioral phenotypes (243)(244)(245)(246). Moreover, the hippocampus has lower 5-HT, acetylcholine, dopamine, and histamine content in the BTBR animals than in the C57BL/6J strain (246-248).…”