Non-diagnostic symptoms in a mouse model of autism in relation to neuroanatomy: the BTBR strain reinvestigated

Abstract

Several mouse models of autism spectrum disorder (ASD), including the BTBR T + tf/J (BTBR) inbred strain, display a diverse array of behavioral deficits with particular face validity. Here we propose that phenotyping these preclinical models of ASD should avoid excessive reliance on appearance validity of the behavioral observations. BTBR mice were examined in three non-diagnostic symptoms modalities, beside an anatomical investigation for construct validity. The BTBR strain displayed poor sensorimotor integration as reflected by shorter stride length and greater latency on the balance beam task (BBT) when compared with C57BL/6 (B6) controls. Also, locomotor indices in the open-field task (OFT) revealed that BTBR mice traveled longer distances with a remarkably faster exploration than the B6 group in favor of hyperactivity and impulsiveness. Furthermore, analysis of spatial performance including search strategies in the Morris water task (MWT) indicated spatial impairment in the BTBR strain due to failure to employ spatial strategies during navigation. Quantitative cytoarchitectonics and volumetric examinations also indicated abnormal cortical and subcortical morphology in the BTBR mice. The results are discussed in relation to the neuroanatomical correlates of motor and cognitive impairments in the BTBR strain. We conclude that non-diagnostic autistic-like symptoms in the BTBR mouse strain can be impacted by autism risk factors in a similar way than the traditional diagnostic signs.

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.…”

Regional Differences in Brain Plasticity and Behaviour as a Function of Sex and Enrichment Type: Oxytocin Matters

“…Balance beam task (BBT). The BBT was used to test sensorimotor integration, motor coordination and balance (86). Animals were placed on one end of an aluminum square bar (2×2 cm diameter, 130 cm long, and 75 cm high) and their home cage was located at the other end of the bar.…”

Heritability of the Mouse Brain Connectome

“…4. BTBR T+ Itpr3tf/J (BTBR) is a common inbred strain with well-known behavioral and neuroanatomical abnormalities including a highly penetrant callosal defect [42] [43] [44]. BTBR is a Mus musculus domesticus with a brain weight of 487 ± 3.9 mg, close to that of B6 (n = 51)…”

“…The first three strains have comparatively normal CNS structure and connections, whereas BTBR is an acallosal strain [42] [43] [44]. There is a 20% range of difference in mean brain volumes among these strains; B6 and BTBR have relatively large brains, whereas D2 and CAST have smaller brains [39].…”