Vesicular glutamate transporters define two sets of glutamatergic afferents to the somatosensory thalamus and two thalamocortical projections in the mouse

Center for Neuroscience, University of California Davis, Davis, California 95616-8798, USA.
The Journal of Comparative Neurology (Impact Factor: 3.23). 03/2008; 507(2):1258-76. DOI: 10.1002/cne.21592
Source: PubMed


The ventral posterior nucleus of the thalamus (VP) receives two major sets of excitatory inputs, one from the ascending somatosensory pathways originating in the dorsal horn, dorsal column nuclei, and trigeminal nuclei, and the other originating from the cerebral cortex. Both systems use glutamate as neurotransmitter, as do the thalamocortical axons relaying somatosensory information from the VP to the primary somatosensory cortex (SI). The synapses formed by these projection systems differ anatomically, physiologically, and in their capacity for short-term synaptic plasticity. Glutamate uptake into synaptic vesicles and its release at central synapses depend on two isoforms of vesicular glutamate transporters, VGluT1 and VGluT2. Despite ample evidence of their complementary distribution, some instances exist of co-localization in the same brain areas or at the same synapses. In the thalamus, the two transcripts coexist in cells of the VP and other nuclei but not in the posterior or intralaminar nuclei. We show that the two isoforms are completely segregated at VP synapses, despite their widespread expression throughout the dorsal and ventral thalamus. We present immunocytochemical, ultrastructural, gene expression, and connectional evidence that VGluT1 in the VP is only found at corticothalamic synapses, whereas VGluT2 is only found at terminals made by axons originating in the spinal cord and brainstem. By contrast, the two VGluT isoforms are co-localized in thalamocortical axon terminals targeting layer IV, but not in those targeting layer I, suggesting the presence of two distinct projection systems related to the core/matrix pattern of organization of thalamocortical connectivity described in other mammals.

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    • ") as well as in different parts of the cortex (Graziano et al. 2008; Hackett et al. 2011). Further, a large body of literature exists to demonstrate the developmental over-production of synapses followed by pruning for neural circuits to achieve adult patterns of connectivity across different species (Ebbesson 1980; Greenough et al. 1987; Luo and O'Leary 2005; Rakic et al. 1986). "
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    ABSTRACT: We had earlier demonstrated a neurofilament-rich plexus of axons in the presumptive human auditory cortex during fetal development which became adult-like during infancy. To elucidate the origin of these axons, we studied the expression of the vesicular glutamate transporters (VGLUT) 1 and 2 in the human auditory cortex at different stages of development. While VGLUT-1 expression predominates in intrinsic and cortico-cortical synapses, VGLUT-2 expression predominates in thalamocortical synapses. Levels of VGLUT-2 mRNA were higher in the auditory cortex before birth compared to postnatal development. In contrast, levels of VGLUT-1 mRNA were low before birth and increased during postnatal development to peak during childhood and then began to decrease in adolescence. Both VGLUT-1 and VGLUT-2 proteins were present in the human auditory cortex as early as 15GW. Further, immunohistochemistry revealed that the supra- and infragranular layers were more immunoreactive for VGLUT-1 compared to that in Layer IV at 34GW and this pattern was maintained until adulthood. As for VGLUT-1 mRNA, VGLUT-1 synapses increased in density between prenatal development and childhood in the human auditory cortex after which they appeared to undergo attrition or pruning. The adult pattern of VGLUT-2 immunoreactivity (a dense band of VGLUT-2-positive terminals in Layer IV) also began to appear in the presumptive Heschl's gyrus at 34GW. The density of VGLUT-2-positive puncta in Layer IV increased between prenatal development and adolescence, followed by a decrease in adulthood, suggesting that thalamic axons which innervate the human auditory cortex undergo pruning comparatively late in development.
    Brain Structure and Function 10/2015; DOI:10.1007/s00429-015-1124-6 · 5.62 Impact Factor
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    • "Cell subtypes that were filled with Lucifer yellow (LY) were identified either by retrograde labeling or by agglutinin labeling. Input sources were labeled by antibody staining with the vesicular glutamate transporter type 1 (VGluT1) or type 2 (VGluT2) to distinguish corticocortical and thalamocortical inputs, respectively (Fujiyama et al. 2001; Graziano et al. 2008). Putative synapses were identified by apposition of presynaptic label to postsynaptic cells observed with confocal laser scanning microscopy (CLSM) and validated by electron microscopic (EM) reconstructions. "
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    ABSTRACT: Most glutamatergic inputs in the neocortex originate from the thalamus or neocortical pyramidal cells. To test whether thalamocortical afferents selectively innervate specific cortical cell subtypes and surface domains, we investigated the distribution patterns of thalamocortical and corticocortical excitatory synaptic inputs in identified postsynaptic cortical cell subtypes using intracellular and immunohistochemical staining combined with confocal laser scanning and electron microscopic observations in 2 thalamorecipient sublayers, lower layer 2/3 (L2/3b) and lower layer 5 (L5b) of rat frontal cortex. The dendrites of GABAergic parvalbumin (PV) cells preferentially received corticocortical inputs in both sublayers. The somata of L2/3b PV cells received thalamic inputs in similar proportions to the basal dendritic spines of L2/3b pyramidal cells, whereas L5b PV somata were mostly innervated by cortical inputs. The basal dendrites of L2/3b pyramidal and L5b corticopontine pyramidal cells received cortical and thalamic glutamatergic inputs in proportion to their local abundance, whereas crossed-corticostriatal pyramidal cells in L5b exhibited a preference for thalamic inputs, particularly in their distal dendrites. Our data demonstrate an exquisite selectivity among thalamocortical afferents in which synaptic connectivity is dependent on the postsynaptic neuron subtype, cortical sublayer, and cell surface domain. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail:
    Cerebral Cortex 06/2015; DOI:10.1093/cercor/bhv124 · 8.67 Impact Factor
    • "The use of a VGLUT isoform within a given projection is demonstrated by correlation of VGLUT mRNA labeling in neuronal cell bodies with VGLUT protein label in their respective terminals. This method appears to identify similar types of VGLUT1-and VGLUT2-positive projections between brain regions (Herzog et al., 2001; Kaneko and Fujiyama, 2002; Fremeau et al., 2004b; Graziano et al., 2008; Balaram et al., 2013), but the mRNA and protein distribution patterns of either VGLUT isoform may vary between species to some extent. For example, VGLUT2 mRNA is only expressed in a subset of layers in the primary visual cortex (V1) of rodents (Hisano et al., 2000; Fremeau et al., 2004b) but is found throughout the superficial layers of V1 in primates (Balaram et al., 2013). "
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    ABSTRACT: Vesicular glutamate transporter (VGLUT) proteins regulate the storage and release of glutamate from synapses of excitatory neurons. Two isoforms, VGLUT1 and VGLUT2, are found in most glutamatergic projections across the mammalian visual system, and appear to differentially identify subsets of excitatory projections between visual structures. To expand current knowledge on the distribution of VGLUT isoforms in highly visual mammals, we examined the mRNA and protein expression patterns of VGLUT1 and VGLUT2 in the lateral geniculate nucleus (LGN), superior colliculus, pulvinar complex, and primary visual cortex (V1) in tree shrews (Tupaia belangeri), which are closely related to primates but classified as a separate order (Scandentia). We found that VGLUT1 was distributed in intrinsic and corticothalamic connections, whereas VGLUT2 was predominantly distributed in subcortical and thalamocortical connections. VGLUT1 and VGLUT2 were coexpressed in the LGN and in the pulvinar complex, as well as in restricted layers of V1, suggesting a greater heterogeneity in the range of efferent glutamatergic projections from these structures. These findings provide further evidence that VGLUT1 and VGLUT2 identify distinct populations of excitatory neurons in visual brain structures across mammals. Observed variations in individual projections may highlight the evolution of these connections through the mammalian lineage. This article is protected by copyright. All rights reserved.
    The Journal of Comparative Neurology 12/2014; 523(12). DOI:10.1002/cne.23727 · 3.23 Impact Factor
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