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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    • "Three homologous subtypes (VGLUT1–3) have been identified in the mammalian CNS (Takamori et al., 2000, 2001, Fremeau et al., 2002), in which VGLUT1 and 2 have been studied most extensively. Occasionally, VGLUT1 and VGLUT2 co-localize, such as in the mossy fibers of the cerebellum (Hioki et al., 2003), however, generally, the spatial expression profiles of the two subtypes are distinct from each other throughout the brain (Fremeau et al., 2001; Kaneko et al., 2002; Hioki et al., 2003; Graziano et al., 2008; Balaram et al., 2015). The cochlear nucleus (CN) is the first target of the VIIIth nerve and contains a number of different regions, which are defined by their relative locations and composition of cell types (Fig. 1). "
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    ABSTRACT: Vesicular glutamate transporters 1 and 2 (VGLUT1 and VGLUT2) have distinct distributions in the cochlear nucleus that correspond to the sources of the labeled terminals. VGLUT1 is mainly associated with terminals of auditory nerve fibers, whereas VGLUT2 is mainly associated with glutamatergic terminals deriving from other sources that project to the cochlear nucleus (CN), including somatosensory and vestibular terminals. Previous studies in guinea pig have shown that cochlear damage results in a decrease of VGLUT1-labeled puncta and an increase in VGLUT2-labeled puncta. This indicates cross-modal compensation that is of potential importance in somatic tinnitus. To examine whether this effect is consistent across species and to provide a background for future studies, using transgenesis, the current study examines VGLUT expression profiles upon cochlear insult by intracochlear kanamycin injections in the mouse. Intracochlear kanamycin injections abolished ipsilateral ABR responses in all animals and reduced ipsilateral spiral ganglion neuron densities in animals that were sacrificed after four weeks, but not in animals that were sacrificed after three weeks. In all unilaterally deafened animals, VGLUT1 density was decreased in CN regions that receive auditory nerve fiber terminals, i.e. in the deep layer of the dorsal cochlear nucleus (DCN), in the interstitial region where the auditory nerve enters the CN, and in the magnocellular region of the antero- and posteroventral CN. In contrast, density of VGLUT2 expression was upregulated in the fusiform cell layer of the DCN and in the granule cell lamina, which are known to receive somatosensory and vestibular terminals. These results show that a cochlear insult induces cross-modal compensation in the cochlear nucleus of the mouse, confirming previous findings in guinea pig, and that these changes are not dependent on the occurrence of spiral ganglion neuron degeneration.
    Full-text · Article · Dec 2015 · Neuroscience
    • ") 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.
    No preview · Article · Oct 2015 · Brain Structure and Function
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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:
    Full-text · Article · Jun 2015 · Cerebral Cortex
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