VGLUTs define subsets of excitatory neurons and suggest novel roles for glutamate

Fremeau, Robert T.; Voglmaier, Susan M.; Seal, Rebecca P.; Edwards, Robert H.

doi:10.1016/j.tins.2003.11.005

Cited by 666 publications

(606 citation statements)

References 64 publications

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“…The glutamatergic synapses of the cerebellar cortex were recognized on the basis of the topographic distribution in the cerebellar cortex layers and expression of vesicular glutamate transporters, vGluT-1 and/or vGluT-2 [39,40,58-62]. In the present study, we observed that the glutamatergic synapses between the parallel fibre terminals and the dendritic tree of Purkinje neurons frequently display co-localization of vGluT-1 with the three SNARE proteins examined.…”

Section: Discussionmentioning

confidence: 48%

“…In the molecular layer, the glutamatergic synapses are densely distributed in the neuropil, mainly consisting of terminals of parallel fibres and, to a lesser extent, of climbing fibres on the dendritic trees of Purkinje neurons [35-40]. In the same layer, GABAergic synapses are distributed throughout the neuropil and consist mainly of synapses of stellate neuron axon terminals on dendrite trees of Purkinje neurons [41-43].…”

Section: Introductionmentioning

confidence: 99%

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VAMP-2, SNAP-25A/B and syntaxin-1 in glutamatergic and GABAergic synapses of the rat cerebellar cortex

et al. 2011

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BackgroundThe aim of this study was to assess the distribution of key SNARE proteins in glutamatergic and GABAergic synapses of the adult rat cerebellar cortex using light microscopy immunohistochemical techniques. Analysis was made of co-localizations of vGluT-1 and vGluT-2, vesicular transporters of glutamate and markers of glutamatergic synapses, or GAD, the GABA synthetic enzyme and marker of GABAergic synapses, with VAMP-2, SNAP-25A/B and syntaxin-1.ResultsThe examined SNARE proteins were found to be diffusely expressed in glutamatergic synapses, whereas they were rarely observed in GABAergic synapses. However, among glutamatergic synapses, subpopulations which did not contain VAMP-2, SNAP-25A/B and syntaxin-1 were detected. They included virtually all the synapses established by terminals of climbing fibres (immunoreactive for vGluT-2) and some synapses established by terminals of parallel and mossy fibres (immunoreactive for vGluT-1, and for vGluT-1 and 2, respectively). The only GABA synapses expressing the SNARE proteins studied were the synapses established by axon terminals of basket neurons.ConclusionThe present study supplies a detailed morphological description of VAMP-2, SNAP-25A/B and syntaxin-1 in the different types of glutamatergic and GABAergic synapses of the rat cerebellar cortex. The examined SNARE proteins characterize most of glutamatergic synapses and only one type of GABAergic synapses. In the subpopulations of glutamatergic and GABAergic synapses lacking the SNARE protein isoforms examined, alternative mechanisms for regulating trafficking of synaptic vesicles may be hypothesized, possibly mediated by different isoforms or homologous proteins.

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Section: Discussionmentioning

confidence: 48%

Section: Introductionmentioning

confidence: 99%

VAMP-2, SNAP-25A/B and syntaxin-1 in glutamatergic and GABAergic synapses of the rat cerebellar cortex

et al. 2011

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“…The VGLUT3 belongs to the type I phosphate transporter family; and in contrast to VGLUT1 and VGLUT2 it is usually not found in canonical asymmetric glutamatergic synapses, but rather localizes to non-glutamatergic serotonergic, cholinergic or GABAergic neurons and to a small subset of astrocytes (Fremeau et al, 2004;Seal and Edwards, 2006). In the basal forebrain, axonal co-expression of VGLUT3-immunoreactivity was shown for the striatal cholinergic interneurons.…”

Section: Introductionmentioning

confidence: 99%

Vesicular glutamate transporter 3-immunoreactive pericellular baskets ensheath a distinct population of neurons in the lateral septum

Riedel

Westerholz

Braun

et al. 2008

Journal of Chemical Neuroanatomy

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The lateral septum (LS) plays a role in the adjustment of behavioral responses according to environmental demands. This is a complex integrative process wherein a variety of modulatory systems, i.e. cholinergic, dopaminergic and serotonergic projections forming pericellular baskets around LS neurons, are involved.Recently, vesicular glutamate transporter 3 (VGLUT3)-immunoreactive (-ir) structures outlining unlabeled somata and their proximal dendrites were described in the LS. However, the vesicular transporters for acetylcholine and GABA were not or only rarely co-expressed with VGLUT3.In this study, the morphology and distribution of these VGLUT3-ir structures were systematically analyzed revealing that (1) they form distinct pericellular baskets (PBs) displaying variable shapes, (2) they are arranged in a layer-like pattern similar to the terminals of other modulatory systems, (3) beside a few exceptions (e.g., choline acetyltransferase), they are generally not or very sparsely colocalized with other neurochemical markers characterizing major neuron populations or afferent systems of the LS, i.e. calcium-binding proteins, tyrosine hydroxylase, tryptophan hydroxylase, vesicular glutamate transporters 1 (VGLUT1) and 2 (VGLUT2) and the vesicular GABA transporter.Thus, in the LS, a separate population of neurons is covered by VGLUT3-ir PBs. The distribution pattern and the lack of co-localization indicate that the VGLUT3-expressing cells of origin are located in the brainstem and that they could be pure glutamatergic projection neurons-different from the well-defined canonical VGLUT1-and VGLUT2-expressing neurons. Alternatively, they could

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“…Selective expression of a genetic tool in the glutamatergic neurons in hindbrain and spinal cord has been achieved by inserting a transgene under the control of vesicular glutamate transporter 2 (Vglut2) promoter [18]. Vglut2 is the dominant glutamate transporter expressed by in these regions [22,23]. In this transgenic mouse, the genetic tool was found only in Vglut2-positive neurons in the central nervous system and exclusively activated by photostimulation.…”

Section: Genetic Identitymentioning

confidence: 99%

“…Therefore, multiple types of neurons could express the targeted genes. Also, the specific cell types defined with a single gene can be found in multiple regions of the nervous system [18,23].…”

Section: Genetic Identitymentioning

confidence: 99%

Selective Manipulation of Neural Circuits

Park

Carmel

2016

Neurotherapeutics

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Unraveling the complex network of neural circuits that form the nervous system demands tools that can manipulate specific circuits. The recent evolution of genetic tools to target neural circuits allows an unprecedented precision in elucidating their function. Here we describe two general approaches for achieving circuit specificity. The first uses the genetic identity of a cell, such as a transcription factor unique to a circuit, to drive expression of a molecule that can manipulate cell function. The second uses the spatial connectivity of a circuit to achieve specificity: one genetic element is introduced at the origin of a circuit and the other at its termination. When the two genetic elements combine within a neuron, they can alter its function. These two general approaches can be combined to allow manipulation of neurons with a specific genetic identity by introducing a regulatory gene into the origin or termination of the circuit. We consider the advantages and disadvantages of both these general approaches with regard to specificity and efficacy of the manipulations. We also review the genetic techniques that allow gain-and loss-of-function within specific neural circuits. These approaches introduce light-sensitive channels (optogenetic) or drug sensitive channels (chemogenetic) into neurons that form specific circuits. We compare these tools with others developed for circuit-specific manipulation and describe the advantages of each. Finally, we discuss how these tools might be applied for identification of the neural circuits that mediate behavior and for repair of neural connections.

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VGLUTs define subsets of excitatory neurons and suggest novel roles for glutamate

Cited by 666 publications

References 64 publications

VAMP-2, SNAP-25A/B and syntaxin-1 in glutamatergic and GABAergic synapses of the rat cerebellar cortex

VAMP-2, SNAP-25A/B and syntaxin-1 in glutamatergic and GABAergic synapses of the rat cerebellar cortex

Vesicular glutamate transporter 3-immunoreactive pericellular baskets ensheath a distinct population of neurons in the lateral septum

Selective Manipulation of Neural Circuits

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