Abstract
In the central nervous system, microtubule-associated protein 6 (MAP6) is expressed at high levels and is crucial for cognitive abilities. The large spectrum of social and cognitive impairments observed in MAP6-KO mice are reminiscent of the symptoms observed in psychiatric diseases, such as schizophrenia, and respond positively to long-term treatment with antipsychotics. MAP6-KO mice have therefore been proposed to be a useful animal model for these diseases. Here, we explored the brain anatomy in MAP6-KO mice using high spatial resolution 3D MRI, including a volumetric T1w method to image brain structures, and Diffusion Tensor Imaging (DTI) for white matter fiber tractography. 3D DTI imaging of neuronal tracts was validated by comparing results to optical images of cleared brains. Changes to brain architecture included reduced volume of the cerebellum and the thalamus and altered size, integrity and spatial orientation of some neuronal tracks such as the anterior commissure, the mammillary tract, the corpus callosum, the corticospinal tract, the fasciculus retroflexus and the fornix. Our results provide information on the neuroanatomical defects behind the neurological phenotype displayed in the MAP6-KO mice model and especially highlight a severe damage of the corticospinal tract with defasciculation at the location of the pontine nuclei.
Highlights
Microtubule effectors regulate microtubule organization and play key roles during brain development
The results revealed the basis of the neuroanatomical defects in microtubule-associated protein 6 (MAP6)-KO mice, in particular in the corticospinal tract, which connects the subset of layer V cortical neurons to motor neurons and interneurons in the spinal cord
All the results given here are discussed as comparisons between results from MAP6-KO and wild type (WT) mice
Summary
Microtubule effectors regulate microtubule organization and play key roles during brain development. In accordance with the involvement of MAPs in brain disorders, when microtubule-associated protein 6 is deleted in mice (MAP6-KO), severe behavioral disorders are observed, such as locomotor hyperactivity, severe social withdrawal, and cognitive deficits[9,10,11,12,13,14] These animals exhibit abnormalities in glutamatergic and dopaminergic neurotransmission, deficits associated with neuronal and synaptic plasticity and impaired sensorimotor gating[10, 13, 15,16,17,18]. Hypoplasia of long-distance projecting axon tracts, and an absence of the post-commissural fornix[14, 17, 21] These characteristics strongly suggest that MAP6 plays a major role in brain anatomy and white matter tract connectivity. The results revealed the basis of the neuroanatomical defects in MAP6-KO mice, in particular in the corticospinal tract, which connects the subset of layer V cortical neurons to motor neurons and interneurons in the spinal cord
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