Molecular taxonomy of major neuronal classes in the adult mouse forebrain

Department of Biology and National Center for Behavioral Genomics, Brandeis University, MS 008, 415 South Street, Waltham, Massachusetts 02454-9110, USA.
Nature Neuroscience (Impact Factor: 14.98). 02/2006; 9(1):99-107. DOI: 10.1038/nn1618
Source: PubMed

ABSTRACT Identifying the neuronal cell types that comprise the mammalian forebrain is a central unsolved problem in neuroscience. Global gene expression profiles offer a potentially unbiased way to assess functional relationships between neurons. Here, we carried out microarray analysis of 12 populations of neurons in the adult mouse forebrain. Five of these populations were chosen from cingulate cortex and included several subtypes of GABAergic interneurons and pyramidal neurons. The remaining seven were derived from the somatosensory cortex, hippocampus, amygdala and thalamus. Using these expression profiles, we were able to construct a taxonomic tree that reflected the expected major relationships between these populations, such as the distinction between cortical interneurons and projection neurons. The taxonomic tree indicated highly heterogeneous gene expression even within a single region. This dataset should be useful for the classification of unknown neuronal subtypes, the investigation of specifically expressed genes and the genetic manipulation of specific neuronal circuit elements.

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    • "This suggests possible occlusion of relationships in more heterogeneous tissue than in more and more specific cell samples. Ideally, all analyses of this kind would be from single identified neurons (Schulz et al., 2007; Tobin et al., 2009; Kodama et al., 2012), or at least pooled neurons of a defined subclass (Sugino et al., 2006). Single cell data of this quality are technically feasible, although they would require preamplification of mRNA to have enough material for the depth of analyses provided here. "
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    ABSTRACT: Neural networks ultimately arrive at functional output via interaction of the excitability of individual neurons and their synaptic interactions. We investigated the relationships between voltage-gated ion channel and neurotransmitter receptor mRNA levels in mouse spinal cord at four different postnatal time points (P5, P11, P17, and adult) and three different adult cord levels (cervical, thoracic, and lumbosacral) using quantitative RT-PCR. Our analysis and data visualization are novel in that we chose a focal group of voltage-gated channel subunits and transmitter receptor subunits, performed absolute quantitation of mRNA copy number for each gene from a sample, and used multiple correlation analyses and correlation matrices to detect patterns in correlated mRNA levels across all genes of interest. These correlation profiles suggest that postnatal maturation of spinal cord includes changes among channel and receptor subunits that proceed from widespread co-regulation to more refined and distinct functional relationships.
    Neuroscience 07/2014; 277. DOI:10.1016/j.neuroscience.2014.07.012 · 3.33 Impact Factor
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    • "The technique also identifies a series of 'marker' genes and proteins that can be used to subdivide, label, monitor, and manipulate subpopulations of interest. This procedure has proved valuable in other sensory processing nodes such as the medial vestibular nucleus (MVN) (Sugino et al., 2005; Kodama et al., 2012). Gene expression profiling in the MVN identified six distinct neuronal subpopulations. "
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    ABSTRACT: In this perspective, we propose the absence of detailed information regarding spinal cord circuits that process sensory information remains a major barrier to advancing analgesia. We highlight recent advances showing that functionally discrete populations of neurons in the spinal cord dorsal horn (DH) play distinct roles in processing sensory information. We then discuss new molecular, electrophysiological, and optogenetic techniques that can be employed to understand how DH circuits process tactile and nociceptive information. We believe this information can drive the development of entirely new classes of pharmacotherapies that target key elements in spinal circuits to selectively modify sensory function and blunt pain.
    Frontiers in Pharmacology 02/2014; 5:22. DOI:10.3389/fphar.2014.00022
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    • "Studies of transcriptional events involved in the development and function of neocortical layers have been greatly advanced with the emergence of high-throughput transcriptome-profiling techniques. A number of studies have analyzed the transcriptome of different mouse neocortical layers and/or areas at specific developmental time points (Arlotta et al., 2005; Belgard et al., 2011; Chen et al., 2005; Dillman et al., 2013; Han et al., 2011; Lein et al., 2007; Lyckman et al., 2008; Rossner et al., 2006; Sugino et al., 2006). Also, these studies have largely focused on the expression of protein-coding mRNA, providing limited information on noncoding RNAs (ncRNAs), which play an important role in neural development and function (McNeill and Van Vactor, 2012). "
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    ABSTRACT: The hallmark of the cerebral neocortex is its organization into six layers, each containing a characteristic set of cell types and synaptic connections. The transcriptional events involved in laminar development and function still remain elusive. Here, we employed deep sequencing of mRNA and small RNA species to gain insights into transcriptional differences among layers and their temporal dynamics during postnatal development of the mouse primary somatosensory neocortex. We identify a number of coding and noncoding transcripts with specific spatiotemporal expression and splicing patterns. We also identify signature trajectories and gene coexpression networks associated with distinct biological processes and transcriptional overlap between these processes. Finally, we provide data that allow the study of potential miRNA and mRNA interactions. Overall, this study provides an integrated view of the laminar and temporal expression dynamics of coding and noncoding transcripts in the mouse neocortex and a resource for studies of neurodevelopment and transcriptome.
    Cell Reports 02/2014; DOI:10.1016/j.celrep.2014.01.036 · 7.21 Impact Factor


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