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Role of glutamate in locomotor rhythm generating neuronal circuitry
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics. (Kullander)
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2006 (English)In: Journal of Physiology - Paris, ISSN 0928-4257, E-ISSN 1769-7115, Vol. 100, no 5-6, 297-303 p.Article in journal (Refereed) Published
Abstract [en]

Central pattern generators (CPGs) are defined as neuronal circuits capable of producing a rhythmic and coordinated output without the influence of sensory input. The locomotor and respiratory neuronal circuits are two of the better-characterized CPGs, although much work remains to fully understand how these networks operate. Glutamatergic neurons are involved in most neuronal circuits of the nervous system and considerable efforts have been made to study glutamate receptors in nervous system signaling using a variety of approaches. Because of the complexity of glutamate-mediated signaling and the variety of receptors triggered by glutamate, it has been difficult to pinpoint the role of glutamatergic neurons in neuronal circuits. In addition, glutamate is an amino acid used by every cell, which has hampered identification of glutamatergic neurons. Glutamatergic excitatory neurotransmission is dependent on the release from glutamate-filled presynaptic vesicles loaded by three members of the solute carrier family, Slc17a6-8, which function as vesicular glutamate transporters (VGLUTs). Recent data describe that Vglut2 (Slc17a6) null mutant mice die immediately after birth due to a complete loss of the stable autonomous respiratory rhythm generated by the pre-Bötzinger complex. Surprisingly, we found that basal rhythmic locomotor activity is not affected in Vglut2 null mutant embryos. With this perspective, we discuss data regarding presence of VGLUT1, VGLUT2 and VGLUT3 positive neuronal populations in the spinal cord.

Place, publisher, year, edition, pages
2006. Vol. 100, no 5-6, 297-303 p.
Keyword [en]
Central nervous system, Development, Movement, Neuronal network, Physiology, Transmitter
National Category
Medical and Health Sciences Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-14472DOI: 10.1016/j.jphysparis.2007.05.001ISI: 000249834800009PubMedID: 17618093OAI: oai:DiVA.org:uu-14472DiVA: diva2:42242
Available from: 2008-01-30 Created: 2008-01-30 Last updated: 2017-12-11Bibliographically approved
In thesis
1. Studies of Spinal Motor Control Networks in Genetically Modified Mouse Models
Open this publication in new window or tab >>Studies of Spinal Motor Control Networks in Genetically Modified Mouse Models
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Spinal neurons are important in several aspects motor control. For example, the neurons essential for locomotor movements reside in the ventral spinal cord. In this thesis, different motor control functions are being related to neuronal populations defined by their common expression of a gene.

First, a targeted disruption of the gene for vesicular glutamate transporter 2 (Vglut2/ Slc17a6) is described. The mutant animals die at birth because of their inability to breathe. The neuronal network in the brainstem, responsible for inspiration, was shown to become non-functional by the targeted deletion of Vglut2. To our surprise, it was still possible to induce rhythmic activity with normal left/right alternation in spinal cords isolated from VGLUT2-null embryos. Inconsistent reports of Vglut1 expression in the spinal cord made us re-evaluate the Vglut1 and Vglut2 expressions. While Vglut2 expression was widespread in the spinal cord, Vglut1 expression was restricted to a few cells dorsal to the central canal.  Taken together, the data suggest that, glutamatergic signaling is mandatory to drive the bilateral breathing, but not needed for coordination of basal alternating spinal locomotor rhythm.

Next, a screen for genes with restricted ventral expression was made. Some of the genes found could be connected to the characteristics of specific neuronal cell populations. For example, fast motor neurons were shown to express the genes Calca and Chodl. Further, we found the Chrna2 expression selectively in putative Renshaw cells. It seems likely that the gene product, the alpha2 subunit of the nicotinergic receptor, could be linked to the unique connection of motor neurons to Renshaw cells. We used the Chrna2 promoter to drive expression of Cre recombinase in a transgenic mouse. The Cre activity was present in most neurons labeled with Renshaw cell markers, which should make it a useful tool for functional studies of this population. The studies presented here show how the genes expressed in subsets of neurons can be used to target populations of neurons for functional studies of neuronal systems.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 45 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 497
Keyword
acetyl choline, central nervous system, central pattern generator, Cre recombinase, development, genetic screen, glutamate, interneuron, motor neuron, mouse, mouse genetics, movement, network, neuronal network, nicotinic receptors, physiology, Renshaw cell, rhythm, spinal cord, transmitter
National Category
Neurosciences Neurosciences Physiology Physiology Physiology
Research subject
Developmental Neurosciences
Identifiers
urn:nbn:se:uu:diva-109889 (URN)978-91-554-7654-0 (ISBN)
Public defence
2009-12-11, B22, BMC, Husarg 3, Uppsala, 09:00 (English)
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Supervisors
Available from: 2009-11-20 Created: 2009-10-29 Last updated: 2009-11-20Bibliographically approved

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Gezelius, HenrikWallén-Mackenzie, ÅsaEnjin, AndersLagerström, MalinKullander, Klas

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