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.
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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    ABSTRACT: The development of the mammalian neocortex relies heavily on subplate. The proportion of this cell population varies considerably in different mammalian species. Subplate is almost undetectable in marsupials, forms a thin, but distinct layer in mouse and rat, a larger layer in carnivores and big-brained mammals as pig, and a highly developed embryonic structure in human and non-human primates. The evolutionary origin of subplate neurons is the subject of current debate. Some hypothesize that subplate represents the ancestral cortex of sauropsids, while others consider it to be an increasingly complex phylogenetic novelty of the mammalian neocortex. Here we review recent work on expression of several genes that were originally identified in rodent as highly and differentially expressed in subplate. We relate these observations to cellular morphology, birthdating, and hodology in the dorsal cortex/dorsal pallium of several amniote species. Based on this reviewed evidence we argue for a third hypothesis according to which subplate contains both ancestral and newly derived cell populations. We propose that the mammalian subplate originally derived from a phylogenetically ancient structure in the dorsal pallium of stem amniotes, but subsequently expanded with additional cell populations in the synapsid lineage to support an increasingly complex cortical plate development. Further understanding of the detailed molecular taxonomy, somatodendritic morphology, and connectivity of subplate in a comparative context should contribute to the identification of the ancestral and newly evolved populations of subplate neurons.
    Frontiers in Neuroanatomy 04/2011; 5:25. DOI:10.3389/fnana.2011.00025 · 3.54 Impact Factor
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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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    ABSTRACT: The sensory cortex is subject to continuous remodelling during early development and throughout adulthood. This process is important for establishing normal brain function and is dependent on cholinergic modulation via muscarinic receptors. Five muscarinic receptor genes encode five unique receptor subtypes (M1-5). The distributions and functions of each subtype vary in central and peripheral systems. In the brain, the M1 receptor is most abundant in the cerebral cortex, where its immunoreactivity peaks transiently during early development. This likely signifies the importance of M1 receptor in the development and maintenance of normal cortical function. Several lines of study have outlined the roles of M1 receptors in the development and plasticity of the auditory cortex. For example, M1-knockout reduces experience-dependent plasticity and disrupts tonotopic mapping in the adult mouse auditory cortex. Further evidence demonstrates a role for M1 in neurite outgrowth and hence determining the structure of cortical neurons. The disruption of tonotopic maps in M1-knockout mice may be linked to alterations in thalamocortical connectivity, because the targets of thalamocortical afferents (layer IV cortical neurons) appear less mature in M1 knockouts. Herein we review the literature to date concerning M1 receptors in the auditory cortex and consider some future directions that will contribute to our understanding.
    Molecular Brain 10/2010; 3(1):29. DOI:10.1186/1756-6606-3-29 · 4.90 Impact Factor
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    ABSTRACT: We have extracted brain functional networks from fMRI data based on temporal correlations of voxel activities during the rest and task periods. The goal of our preliminary research was to study the topology of these networks in terms of small-world and scale-free properties. The small-world property was quite clearly evident whereas the scale-free character was less obvious, especially in the rest condition. In addition, there were some differences between the rest and task functional brain networks as well as between subjects. We discuss the relation of properties of functional brain networks to the topological properties of the underlying anatomical networks, which are largely dependent upon genetic instructions during brain development.
    01/1970: pages 111-118;
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