Corpus callosum and visual cortex of mice with deletion of the NMDA-NR1 receptor: I. Accelerated development of callosal projection neurons

• Published in: Brain research. Developmental brain research Vol. 144; no. 2; pp. 121 - 133
• Main Authors: Elberger, Andrea J, Deng, Jinbo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10.09.2003
• Subjects: Animals; Animals, Newborn; Carbocyanines - metabolism; Cell Surface Extensions - physiology; Corpus callosum; Corpus Callosum - cytology; Corpus Callosum - embryology; Corpus Callosum - physiology; Development; Embryo, Mammalian; Embryonic and Fetal Development - physiology; Female; Gene Deletion; Gene–dose effect; Genotype; Knockout; Male; Mice; Mice, Inbred C57BL; Mice, Knockout - embryology; Mice, Knockout - physiology; Mice, Transgenic; Neurons - physiology; NMDA-NR1 receptor; Polymerase Chain Reaction - methods; Receptors, N-Methyl-D-Aspartate - genetics; Visual cortex; Visual Cortex - cytology; Visual Cortex - embryology; Visual Cortex - physiology; Visual cortex; Neurotransmitters, modulators, transporters and receptors; Development; Gene–dose effect; Corpus callosum; Knockout; NMDA-NR1 receptor
• ISSN: 0165-3806
• DOI: 10.1016/S0165-3806(03)00156-1

Many pharmacological experiments show that the ionotropic receptor NMDA has both neurotrophic and neuroexcitotoxic effects. The neurotrophic function is manifested in many ways including acceleration of neuronal development, enhancement of neuronal migration, neuroprotection, blockage of apoptosis, prevention of aging and prematurity, as well as effects on synaptic plasticity and synaptogenesis. On the other hand, the neuroexcitotoxic function is manifested in its role in neurological and psychiatric diseases such as epilepsy, Parkinson’s disease and schizophrenia. The present study explores the consequences of complete and partial absence of NMDA-NR1 receptors throughout development. Using DiI tracing in vitro, the development of corpus callosum projection neurons in transgenic mice with deletion of the NMDA-NR1 receptor was observed in visual cortex. Compared to littermate controls, the histogenesis and neuronal development of corpus callosum cells of origin was found to be accelerated in NR1−/− mice. That is, the corpus callosum projection neurons in NR1 knockout mice developed earlier and faster than in littermate heterozygous and wild-type mice. However, the corpus callosum projection neurons in NR1 heterozygous mice developed earlier and faster than in littermate wild-type mice. This suggests that NMDA-NR1 receptors are involved in sequencing and/or temporal regulation of neuronal development, and that there is a gene–dose effect. Studies from other laboratories suggest that the observed phenomenon of prematurity or accelerated development is a direct effect of altered expression of genes found in mice with deletion of the NMDA-NR1 receptor.