Genes Involved in the Formation of the Earliest Cortical Circuits

Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
Novartis Foundation symposium 02/2007; 288:212-24; discussion 224-9, 276-81. DOI: 10.1002/9780470994030.ch15
Source: PubMed


Building the brain is like erecting a house of cards. The early connections provide the foundation of the adult structure, and disruption of these may be the source of many developmental flaws. Cerebral cortical developmental disorders (including schizophrenia and autism) and perinatal injuries involve cortical neurons with early connectivity. The major hindrance of progress in understanding the early neural circuits during cortical development and disease has been the lack of reliable markers for specific cell populations. Due to the advance of powerful approaches in gene expression analysis and the utility of models with reporter gene expressions in specific cortical cell types, our knowledge of the early cortical circuits is rapidly increasing. With focus on the sub-plate, layer VI and layer V projection neurons, we shall illustrate the progress made in the understanding of their neurochemical properties, physiological characteristics and their integration into the early intracortical and extracortical circuitry. This field benefited from recent developments in mouse genetics in generating models with subtype specific gene expression patterns, powerful cell dissection and separation methods combined with microarray analysis. The emergence of cortical cell type specific biomarkers will not only help neuropathological diagnosis, but will also eventually reveal the causal relations in the pathogenesis of various cortical developmental disorders.

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    • "Marsupials, many of which do not have a cytoarchitectonically distinct subplate layer (Harman et al., 1995; Reep, 2000), and insectivores would represent an intermediate evolutionary stage where the thalamic afferents extend in an oblique fashion directly toward the cortical plate or, as it was described in hedgehog, thalamocortical axons arrive to the cortex through both above and below the cortical plate. This organization would be comparable to the p35−/− mutant mouse where the thalamic afferents also ascend to the middle of the cortical plate in oblique fascicles because subplate neurons are displaced there due to migration defects (Rakic et al., 2006; Molnár et al., 2007). In both (marsupial and p35−/− phenotype ) the subplate marker distribution does not label a band at the bottom of the cortex as in wild-type mice, but rather labels cells within the cortical plate. "
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    • "Sensory cortices begin to form and make intracortical and subcortical connections early in the developmental regime, and the auditory cortex is no exception. The cortical plate in mice is present as early as embryonic day (E) 11 [1], at about the same time as cochlear hair cells are forming [2,3]. During early development several key neuronal projections make connections in the cortex, and here we focus on two: one consists of glutamatergic axons from thalamic relay cells, through which the cortex receives the majority of its environmental input [4], and the other comprises cholinergic axons, primarily from the basal forebrain. "
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