Sugino, et al. Molecular taxonomy of major neuronal classes in the adult mouse forebrain. Nat. Neurosci. 9, 99-107

Department of Biology, Brandeis University, Волтам, Massachusetts, United States
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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    • "All P-values from the bioinformatic analyses were adjusted using the Benjamini–Hochberg method. For cell types and immune response enrichment, we used the following lists of genes: neurons, astrocytes and oligodendrocytes (Cahoy et al, 2008), microglia (cured from Oldham et al, 2008), and glutamate/GABA (Sugino et al, 2006). For cross species comparison, we used lists from alcohol vapor-treated rats (Tapocik et al, 2013) and human alcoholics (Lewohl et al, 2011) to identify conserved alcoholresponsive microRNAs. "
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    ABSTRACT: Local translation of mRNAs in the synapse plays a major role in synaptic structure and function. Chronic alcohol use causes persistent changes in synaptic mRNA expression, possibly mediated by microRNAs localized in the synapse. We profiled the transcriptome of synaptoneurosomes (SN) obtained from the amygdala of mice that consumed 20% ethanol (alcohol) in a 30-day continuous two-bottle choice test to identify the microRNAs that target alcohol-induced mRNAs. SN are membrane vesicles containing pre- and post-synaptic compartments of neurons and astroglia and are a unique model for studying the synaptic transcriptome. We previously showed that chronic alcohol regulates mRNA expression in a coordinated manner. Here, we examine microRNAs and mRNAs from the same samples to define alcohol-responsive synaptic microRNAs and their predicted interactions with targeted mRNAs. The aim of the study was to identify the microRNA-mRNA synaptic interactions that are altered by alcohol. This was accomplished by comparing the effect of alcohol in SN vs. total homogenate preparations from the same samples. We used a combination of unbiased bioinformatics methods (differential expression, correlation, co-expression, microRNA-mRNA target prediction, co-targeting and cell type specific analyses) to identify key alcohol-sensitive microRNAs. Prediction analysis showed that a subset of alcohol-responsive microRNAs was predicted to target many alcohol-responsive mRNAs, providing a bidirectional analysis for identifying microRNA-mRNA interactions. We found microRNAs and mRNAs with overlapping patterns of expression that correlated with alcohol consumption. Cell-type specific analysis revealed that a significant number of alcohol-responsive mRNAs and microRNAs were unique to glutamate neurons and were predicted to target each other. Chronic alcohol appears to perturb the coordinated microRNA regulation of mRNAs in SN, a mechanism that may explain the aberrations in synaptic plasticity affecting the alcoholic brain.Neuropsychopharmacology accepted article preview online, 24 June 2015. doi:10.1038/npp.2015.179.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 06/2015; DOI:10.1038/npp.2015.179 · 7.83 Impact Factor
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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 · 3.80 Impact Factor
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