Neuroanatomical characterization of the cellular and axonal architecture of subcortical band heterotopia in the BXD29-Tlr4lps-2J/J mouse cortex.
Subcortical band heterotopia (SBH) are malformations of the human cerebral cortex typically associated with epilepsy and cognitive delay/disability. Rodent models of SBH have demonstrated strong face validity as they are accompanied by both cognitive deficits and spontaneous seizures or reduced seizure threshold. BXD29-Tlr4lps-2J/J recombinant inbred mice display striking bilateral SBH, partial callosal agenesis, morphological changes in subcortical structures of the auditory pathway, and display sensory deficits in behavioral tests (Rosen et al., 2013; Truong et al., 2013, 2015). Surprisingly, these mice show no cognitive deficits and have a higher seizure threshold to chemi-convulsive treatment (Gabel et al., 2013) making them different than other rodent SBH models described previously. In the present report, we perform a detailed characterization of the cellular and axonal constituents of SBH in BXD29-Tlr4lps-2J/J mice and demonstrate that various types of interneurons and glia as well as cortical and subcortical projections are found in SBH. In addition, the length of neuronal cilia was reduced in SBH compared to neurons in the overlying and adjacent normotopic cortex. Finally, we describe additional and novel malformations of the hippocampus and neocortex present in BXD29-Tlr4lps-2J/J mice. Together, our findings in BXD29-Tlr4lps-2J/J mice are discussed in the context of the known neuroanatomy and phenotype of other SBH rodent models.
Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, Old Westbury, NY 11568, USA. Electronic address: rramos02@nyit.edu.
Raddy L
RL
Ramos
Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, Old Westbury, NY 11568, USA.
Alyssa R
AR
Toia
Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, Old Westbury, NY 11568, USA.
Daniel M
DM
Pasternack
Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, Old Westbury, NY 11568, USA.
Timothy P
TP
Dotzler
Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, Old Westbury, NY 11568, USA.
Joshua A
JA
Cuoco
Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, Old Westbury, NY 11568, USA.
Anthony W
AW
Esposito
Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL 32610-0244, USA.
Megan M
MM
Le
Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL 32610-0244, USA.
Alexander K
AK
Parker
Department of Developmental Neurobiology, NY State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA; Department of Physiology & Pharmacology and Department of Neurology, SUNY Downstate Medical Center, Brooklyn, NY, USA.
Jeffrey H
JH
Goodman
Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL 32610-0244, USA. Electronic address: msarkisian@ufl.edu.
Matthew R
MR
Sarkisian
D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000002:abnormalities / Q000378:metabolism*; D054221:Classical Lissencephalies and Subcortical Band Heterotopias / Q000378:metabolism*; D004195:Disease Models, Animal; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D019579:Neocortex / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism*; D010641:Phenotype; D012640:Seizures / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
D008869:Microtubule-Associated Proteins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4
malformation; neocortex; neuronal migration; subcortical band heterotopia