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Studies of Spinal M...
Studies of Spinal Motor Control Networks in Genetically Modified Mouse Models
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- Gezelius, Henrik, 1977- (author)
- Uppsala universitet,Institutionen för neurovetenskap,Genetisk utvecklingsbiologi,Formation and function of neuronal circuits
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- Kullander, Klas, Dr (thesis advisor)
- Uppsala universitet,Genetisk utvecklingsbiologi
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- Ebendal, Ted, Professor (thesis advisor)
- Uppsala universitet,Medicinsk utvecklingsbiologi
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- Goulding, Martyn, Professor (opponent)
- Lunds universitet
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(creator_code:org_t)
- ISBN 9789155476540
- Uppsala : Acta Universitatis Upsaliensis, 2009
- English 45 s.
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Series: Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, 1651-6206 ; 497
- Related links:
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
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
- Neuroscience
- Neurovetenskap
- Neurobiology
- Neurobiologi
- Molecular neurobiology
- Molekylär neurobiologi
- Neurophysiology
- Neurofysiologi
- Neurobiology
- Neurobiologi
- medicinsk utvecklings- och neurobiologi
- Developmental Neurosciences
Publication and Content Type
- vet (subject category)
- dok (subject category)
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