Neuroanatomical characterization of the cellular and axonal architecture of subcortical band heterotopia in the BXD29-Tlr4lps-2J/J mouse cortex. (19th November 2016)

• Record Type: Journal Article
• Authors: Ramos, Raddy L.; Toia, Alyssa R.; Pasternack, Daniel M.; Dotzler, Timothy P.; Cuoco, Joshua A.; Esposito, Anthony W.; Le, Megan M.; Parker, Alexander K.; Goodman, Jeffrey H.; Sarkisian, Matthew R.
• Is Part Of: Neuroscience. Volume 337(2016)
• Page Start: 48
• Page End: 65
• Publication Date: 2016-11-19
• Subjects: BDA biotinylated detran amine -- ChAT choline acetyl-transferase -- CR calretinin -- GABA gamma amino-butyric acid -- GAD glutamic acid decarboxylase 67 -- GFAP glial fibrillary acidic protein -- IBA1 ionized calcium-binding adapter protein 1 -- IZ intermediate zone -- MLH molecular layer heterotopia -- NDS normal donkey serum -- NeuN neuronal nuclear marker -- NGS normal goat serum -- NPY neuropeptide-Y -- Olig2 oligodendrocyte transcription factor 2 -- PBS phosphate-buffered saline -- PV parvalbumin -- SBH subcortical band heterotopia -- TH tyrosine hydroxylase; neocortex -- malformation -- subcortical band heterotopia -- neuronal migration; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2016.08.049
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Subcortical band heterotopia in BXD29-Tlr4 lps-2J /J mice contains diverse subtypes of GABAergic neurons. Subcortical band heterotopia in BXD29-Tlr4 lps-2J /J mice contains astrocytes, microglia, and oligodendrocytes. Subcortical and cortical projections are present in subcortical band heterotopia in BXD29-Tlr4 lps-2J /J mice. Neocortical molecular layer heterotopia and hippocampal malformations are also present in BXD29-Tlr4 lps-2J /J mice. Abstract: 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-Tlr4 lps-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-Tlr4 lps-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-Tlr4 lps-2J /J mice. Together, our findings in BXD29-Tlr4 lps-2J /J mice are discussed in the context of the known neuroanatomy and phenotype of other SBH rodent models.