+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Axonal Segregation and Role of the Vesicular Glutamate Transporter VGLUT3 in Serotonin Neurons



Axonal Segregation and Role of the Vesicular Glutamate Transporter VGLUT3 in Serotonin Neurons



Frontiers in Neuroanatomy 10: 39



A subset of monoamine neurons releases glutamate as a cotransmitter due to presence of the vesicular glutamate transporters VGLUT2 or VGLUT3. In addition to mediating vesicular loading of glutamate, it has been proposed that VGLUT3 enhances serotonin (5-HT) vesicular loading by the vesicular monoamine transporter (VMAT2) in 5-HT neurons. In dopamine (DA) neurons, glutamate appears to be released from specialized subsets of terminals and it may play a developmental role, promoting neuronal growth and survival. The hypothesis of a similar developmental role and axonal localization of glutamate co-release in 5-HT neurons has not been directly examined. Using postnatal mouse raphe neurons in culture, we first observed that in contrast to 5-HT itself, other phenotypic markers of 5-HT axon terminals such as the 5-HT reuptake transporter (SERT) show a more restricted localization in the axonal arborization. Interestingly, only a subset of SERT- and 5-HT-positive axonal varicosities expressed VGLUT3, with SERT and VGLUT3 being mostly segregated. Using VGLUT3 knockout mice, we found that deletion of this transporter leads to reduced survival of 5-HT neurons in vitro and also decreased the density of 5-HT-immunoreactivity in terminals in the dorsal striatum and dorsal part of the hippocampus in the intact brain. Our results demonstrate that raphe 5-HT neurons express SERT and VGLUT3 mainly in segregated axon terminals and that VGLUT3 regulates the vulnerability of these neurons and the neurochemical identity of their axonal domain, offering new perspectives on the functional connectivity of a cell population involved in anxiety disorders and depression.

(PDF emailed within 0-6 h: $19.90)

Accession: 057276731

Download citation: RISBibTeXText

PMID: 27147980

DOI: 10.3389/fnana.2016.00039


Related references

Locally collateralizing glutamate neurons in the dorsal raphe nucleus responsive to substance P contain vesicular glutamate transporter 3 (VGLUT3). Journal of Chemical Neuroanatomy 38(4): 273-281, 2010

Nonserotonergic projection neurons in the midbrain raphe nuclei contain the vesicular glutamate transporter VGLUT3. Synapse 63(1): 31-41, 2008

Role of the atypical vesicular glutamate transporter VGLUT3 in l-DOPA-induced dyskinesia. Neurobiology of Disease 87: 69-79, 2016

Role of the vesicular transporter VGLUT3 in retrograde release of glutamate by cerebellar Purkinje cells. Journal of Neurophysiology 105(3): 1023-1032, 2011

Localization of VGLUT3, the vesicular glutamate transporter type 3, in the rat brain. Neuroscience 123(4): 983-1002, 2004

Coincidence of neurokinin 1 receptor with the vesicular glutamate transporter 3 (VGLUT3) in the rat forebrain. Neuroscience Letters 464(3): 188-192, 2009

Comparison of the ontogeny of the vesicular glutamate transporter 3 (VGLUT3) with VGLUT1 and VGLUT2 in the rat retina. Brain Research 1215: 20-29, 2008

The vesicular glutamate transporter VGLUT3 contributes to protection against neonatal hypoxic stress. Journal of Physiology 590(20): 5183-5198, 2013

Vesicular glutamate transporter 1 and vesicular glutamate transporter 2 synapses on cholinergic neurons in the sublenticular gray of the rat basal forebrain: a double-label electron microscopic study. Neuroscience 164(4): 1721-1731, 2010

VGLUT3 (vesicular glutamate transporter type 3) contribution to the regulation of serotonergic transmission and anxiety. Journal of Neuroscience 30(6): 2198-2210, 2010

Vesicular glutamate transporter 3 (VGLUT3) identifies spatially segregated excitatory terminals in the rat substantia nigra. European Journal of Neuroscience 23(4): 1063-1070, 2006

Evidence for a third vesicular glutamate transporter isoform vglut3 cloning,functional characterization and distribution in mouse brain. Society for Neuroscience Abstract Viewer & Itinerary Planner : Abstract No 343 1, 2002

GABAergic basket cells expressing cholecystokinin contain vesicular glutamate transporter type 3 (VGLUT3) in their synaptic terminals in hippocampus and isocortex of the rat. European Journal of Neuroscience 19(3): 552-569, 2004

Impairment of SLC17A8 encoding vesicular glutamate transporter-3, VGLUT3, underlies nonsyndromic deafness DFNA25 and inner hair cell dysfunction in null mice. American Journal of Human Genetics 83(2): 278-292, 2008

The expression of vesicular glutamate transporter 3 and vesicular monoamine transporter 2 induced by brain-derived neurotrophic factor in dorsal root ganglion neurons in vitro. Brain Research Bulletin 100: 93-106, 2014