The Localization of the Brain-Specific Inorganic Phosphate Transporter Suggests a Specific Presynaptic Role in Glutamatergic Transmission

Bellocchio, Elizabeth E.; Hu, Hailan; Pohorille, Alicia; Chan, June; Pickel, Virginia M.; Edwards, Robert H.

doi:10.1523/jneurosci.18-21-08648.1998

Cited by 309 publications

(315 citation statements)

References 55 publications

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“…The observed pattern of VGLUT1 immunoreactivity in the dorsal hippocampus of control mice was consistent with previous reports (Bellocchio et al, 1998;Fremeau et al, 2001;Varoqui et al, 2002) demonstrating widespread expression, with the exception of granule and pyramidal cell layers, and particular enrichment in stratum oriens and radiatum of CA1 as well as the molecular and polymorphic layers of the dentate gyrus (Figure 4a, left). All VGLUT1 staining was abolished by preadsorption of the primary antibody with a VGLUT1 control peptide (data not shown).…”

Section: Intrahippocampal Administration Of Vglut1-targeting Shrna Sesupporting

confidence: 92%

“…VGLUT1 is expressed in a distinct laminar pattern throughout the dorsal hippocampus, with particular enrichment in the polymorphic and molecular cell layers. Localization to strata oriens and radiatum of CA1 suggests expression in terminals of the Schaffer collateral system, presence in stratum lucidum of CA3 represents expression in mossy fiber terminals from dentate granule cells, and stronger labeling in outer regions of the molecular layer of the dentate gyrus indicates preferential localization to perforant path inputs from the entorhinal cortex (Bellocchio et al, 1998;Fremeau et al, 2001;Varoqui et al, 2002). Despite low VGLUT2 expression in the pyramidal layer of CA2 and the granular layer of the dentate gyrus (Fremeau et al, 2001), there is no evidence for coexpression of both transporters within individual nerve terminals (Herzog et al, 2001), and a recent detailed study found no evidence for VGLUT1 expression in hippocampal astrocytes (Li et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

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Lentiviral Delivery of a Vesicular Glutamate Transporter 1 (VGLUT1)-Targeting Short Hairpin RNA Vector Into the Mouse Hippocampus Impairs Cognition

King

Kurian

Qin

et al. 2013

Neuropsychopharmacol

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Glutamate is the principle excitatory neurotransmitter in the mammalian brain, and dysregulation of glutamatergic neurotransmission is implicated in the pathophysiology of several psychiatric and neurological diseases. This study utilized novel lentiviral short hairpin RNA (shRNA) vectors to target expression of the vesicular glutamate transporter 1 (VGLUT1) following injection into the dorsal hippocampus of adult mice, as partial reductions in VGLUT1 expression should attenuate glutamatergic signaling and similar reductions have been reported in schizophrenia. The VGLUT1-targeting vector attenuated tonic glutamate release in the dorsal hippocampus without affecting GABA, and selectively impaired novel object discrimination (NOD) and retention (but not acquisition) in the Morris water maze, without influencing contextual fear-motivated learning or causing any adverse locomotor or central immune effects. This pattern of cognitive impairment is consistent with the accumulating evidence for functional differentiation along the dorsoventral axis of the hippocampus, and supports the involvement of dorsal hippocampal glutamatergic neurotransmission in both spatial and nonspatial memory. Future use of this nonpharmacological VGLUT1 knockdown mouse model could improve our understanding of glutamatergic neurobiology and aid assessment of novel therapies for cognitive deficits such as those seen in schizophrenia.

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Section: Intrahippocampal Administration Of Vglut1-targeting Shrna Sesupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Lentiviral Delivery of a Vesicular Glutamate Transporter 1 (VGLUT1)-Targeting Short Hairpin RNA Vector Into the Mouse Hippocampus Impairs Cognition

King

Kurian

Qin

et al. 2013

Neuropsychopharmacol

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“…Postsynaptic structures were identified as the dendritic spines of granule neurons, traced from the GCL, but the origin of presynaptic axons is less clear. The majority of glutamatergic inputs to the dentate gyrus originate from the entorhinal cortex (43), but cortical inputs mainly terminate in the outer two thirds of the ML (64)(65)(66)(67)(68). The dense arborizations of NGPα RGL stem cells are predominantly contained within the inner third of the ML and GCL, a region where subcortical inputs predominantly terminate (69).…”

Section: Discussionmentioning

confidence: 99%

Fine processes of Nestin-GFP–positive radial glia-like stem cells in the adult dentate gyrus ensheathe local synapses and vasculature

Moss

Gebara

Bushong

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

110

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Adult hippocampal neurogenesis relies on the activation of neural stem cells in the dentate gyrus, their division, and differentiation of their progeny into mature granule neurons. The complex morphology of radial glia-like (RGL) stem cells suggests that these cells establish numerous contacts with the cellular components of the neurogenic niche that may play a crucial role in the regulation of RGL stem cell activity. However, the morphology of RGL stem cells remains poorly described. Here, we used light microscopy and electron microscopy to examine Nestin-GFP transgenic mice and provide a detailed ultrastructural reconstruction analysis of Nestin-GFP-positive RGL cells of the dentate gyrus. We show that their primary processes follow a tortuous path from the subgranular zone through the granule cell layer and ensheathe local synapses and vasculature in the inner molecular layer. They share the ensheathing of synapses and vasculature with astrocytic processes and adhere to the adjacent processes of astrocytes. This extensive interaction of processes with their local environment could allow them to be uniquely receptive to signals from local neurons, glia, and vasculature, which may regulate their fate.adult neurogenesis | adult neural stem cell | neurogenic niche | electron microscopy | hippocampus N eurogenesis in the adult mouse brain primarily occurs within discrete niches, the subventricular zone (SVZ), and the subgranular zone (SGZ) of the dentate gyrus, supplying new neurons to the olfactory bulb and the dentate gyrus, respectively (1-3). Neural stem cells of these niches can be activated to divide and generate other stem cells, astrocytes, or new neurons (4, 5). Newborn neurons of the dentate gyrus have the capacity to integrate into the existing hippocampal circuitry (6-8), influencing processes such as learning and memory (9-11) as well as stress and depression (12).Radial glia-like (RGL) neural stem cells of the SVZ, which supply the olfactory bulb with newborn neurons and astrocytes, express astrocytic markers and form elegant pinwheel structures (13-16). RGL neural stem cells of the adult dentate gyrus also express astrocytic markers, but comprise a heterogeneous population based on the molecular markers they express, the morphologies they exhibit (17-22), and their fate (23-28). Nestin-GFP-positive RGL stem cells account for more than 70% of RGL stem cells in the SGZ of the dentate gyrus (24), but it was recently found that not all Nestin-GFP-positive cells with RGL morphology have stem cell properties (29): type β cells, which arborize in the granule cell layer (GCL) but do not reach the molecular layer (ML) of the dentate gyrus, account for 26% of Nestin-GFP-positive RGL stem cells. They express stem cell (Sox1, Sox2, Prominin 1, GFAP, and Nestin) and astrocytic [GFAP, glial glutamate tranporter 1 (GLT1), and S100β] markers but do not proliferate. In contrast, type α cells, which extend across the GCL and arborize in the inner ML, account for 74% of Nestin-GFP-positive RGL cells. They express stem...

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“…VGLUT1 mRNA and protein is expressed in most pyramidal neurons in situ (Ni et al, 1995;Bellocchio et al, 1998), and VGLUT1-encoded excitatory synapses predominate in adult neocortex (Fremeau et al, 2004a) as they do in differentiated neocortical cultures (DIV21). VGLUT2-expressing puncta are evenly distributed in differentiated cultures, like VGLUT1, but are reduced in number (ϳ25%).…”

Section: Coordinated Endogenous Upregulation Of Vglut1 and Viaat Durimentioning

confidence: 99%

Homeostatic Scaling of Vesicular Glutamate and GABA Transporter Expression in Rat Neocortical Circuits

Gois

Schäfer²,

Defamie³

et al. 2005

J. Neurosci.

174

183

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Homeostatic control of pyramidal neuron firing rate involves a functional balance of feedforward excitation and feedback inhibition in neocortical circuits. Here, we reveal a dynamic scaling in vesicular excitatory (vesicular glutamate transporters VGLUT1 and VGLUT2) and inhibitory (vesicular inhibitory amino acid transporter VIAAT) transporter mRNA and synaptic protein expression in rat neocortical neuronal cultures, using a well established in vitro protocol to induce homeostatic plasticity. During the second and third week of synaptic differentiation, the predominant vesicular transporters expressed in neocortical neurons, VGLUT1 and VIAAT, are both dramatically upregulated. In mature cultures, VGLUT1 and VIAAT exhibit bidirectional and opposite regulation by prolonged activity changes. Endogenous coregulation during development and homeostatic scaling of the expression of the transporters in functionally differentiated cultures may serve to control vesicular glutamate and GABA filling and adjust functional presynaptic excitatory/inhibitory balance. Unexpectedly, hyperexcitation in differentiated cultures triggers a striking increase in VGLUT2 mRNA and synaptic protein, whereas decreased excitation reduces levels. VGLUT2 mRNA and protein are expressed in subsets of VGLUT1-encoded neocortical neurons that we identify in primary cultures and in neocortex in situ and in vivo. After prolonged hyperexcitation, downregulation of VGLUT1/ synaptophysin intensity ratios at most synapses is observed, whereas a subset of VGLUT1-containing boutons selectively increase the expression of VGLUT2. Bidirectional and opposite regulation of VGLUT1 and VGLUT2 by activity may serve as positive or negative feedback regulators for cortical synaptic transmission. Intracortical VGLUT1/VGLUT2 coexpressing neurons have the capacity to independently modulate the level of expression of either transporter at discrete synapses and therefore may serve as a plastic interface between subcortical thalamic input (VGLUT2) and cortical output (VGLUT1) neurons.

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The Localization of the Brain-Specific Inorganic Phosphate Transporter Suggests a Specific Presynaptic Role in Glutamatergic Transmission

Cited by 309 publications

References 55 publications

Lentiviral Delivery of a Vesicular Glutamate Transporter 1 (VGLUT1)-Targeting Short Hairpin RNA Vector Into the Mouse Hippocampus Impairs Cognition

Lentiviral Delivery of a Vesicular Glutamate Transporter 1 (VGLUT1)-Targeting Short Hairpin RNA Vector Into the Mouse Hippocampus Impairs Cognition

Fine processes of Nestin-GFP–positive radial glia-like stem cells in the adult dentate gyrus ensheathe local synapses and vasculature

Homeostatic Scaling of Vesicular Glutamate and GABA Transporter Expression in Rat Neocortical Circuits

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