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Functional Imaging of Spinal Locomotor Networks
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala University. (Klas Kullander Group, Unit of Developmental Genetics)ORCID iD: 0000-0001-9768-9462
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Movement is necessary for the survival of most animals. The spinal cord contains neuronal networks that are capable of motor coordination and of producing different movements. In particular, a very reduced neuronal network in the spinal cord can produce simple rhythmic outputs even in the absence of descending or sensory inputs. This basic circuit was discovered by Thomas Graham Brown (reported in 1911) and is termed central pattern generator. For over a century a large number of studies have been carried out in order to identify the neuronal components that are part of these networks.

In project 1 we focused on Renshaw cells, which are a population of spinal interneurons expressing the alpha-2 subunit of the nicotinic acetylcholine receptors (Chrna2). Renshaw cells are the only identified central targets for motor neuron inputs, and in turn they mediate inhibition of the motor neurons. We analyzed the activity pattern of Renshaw cells on a cell-population level in neonates when the circuit is still developing. At segment 1 of the lumbar spinal cord, Renshaw cells show significantly greater activity response to functional sensory and motor inputs from rostral compared to the caudal segments. Contrarily, the suppression of the monosynaptic stretch reflex was more pronounced when caudal roots were stimulated. Our data underline the importance of sensory input during motor circuit development and help to understand the functional organization of Renshaw cell connectivity.

Several neurons that play distinct roles in locomotor central pattern generation have been identified with the help of genetics. For instance, the V0 population of spinal interneurons are identified by the expression of transcription factor developing brain homeobox 1 (Dbx1). V0 neurons are necessary for producing an alternating rhythm at all locomotor speeds. In project 2 we have looked at a population of dorsally derived ventrally projecting interneurons that express the transcription factor doublesex and mab-3 related transcription factor 3 (Dmrt3). On a behavioral level Dmrt3 neurons are involved in regulating coordination across different locomotor speeds. On a microcircuit level, we have shown that individual Dmrt3 neurons show distinct frequencies of oscillations for a constant locomotor rhythm. In addition, removal of inhibitory neurotransmission from Dmrt3 neurons results in uncoupling of rhythm in motor neurons.

In project 3 the activity patterns in populations of flexor related motor neurons are characterized during fictive locomotion in neonatal mice. An interesting and intriguing finding in project 3 is the presence of multiple rhythmicities in motor neurons. Multiple rhythmicities are seen even when the locomotor output shows a constant frequency.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. , 47 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1190
Keyword [en]
Central pattern generators, two-photon microscopy, locomotor rhythm, multiple rhythmicities, inhibitory neurotransmission
National Category
Neurosciences
Research subject
Neuroscience
Identifiers
URN: urn:nbn:se:uu:diva-280062ISBN: 978-91-554-9500-8 (print)OAI: oai:DiVA.org:uu-280062DiVA: diva2:909950
Public defence
2016-04-27, B22, Biomedical Centre, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2016-04-06 Created: 2016-03-07 Last updated: 2016-04-12
List of papers
1. Topographical organisation of functional sensory and motor inputs to Renshaw cells
Open this publication in new window or tab >>Topographical organisation of functional sensory and motor inputs to Renshaw cells
(English)Manuscript (preprint) (Other academic)
Keyword
Spinal interneuron physiology
National Category
Neurosciences
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-280035 (URN)
Funder
The Swedish Brain Foundation
Available from: 2016-03-07 Created: 2016-03-07 Last updated: 2016-04-12
2. Dmrt3 derived spinal cord neurons regulate locomotor coordination across different speeds
Open this publication in new window or tab >>Dmrt3 derived spinal cord neurons regulate locomotor coordination across different speeds
(English)Manuscript (preprint) (Other academic)
Keyword
progenitor domain, left-right coordination, multiple rhythmicities
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-280060 (URN)
Available from: 2016-03-07 Created: 2016-03-07 Last updated: 2016-04-12
3. A microcircuit analysis of motor neuron behaviour during fictive locomotion
Open this publication in new window or tab >>A microcircuit analysis of motor neuron behaviour during fictive locomotion
(English)Manuscript (preprint) (Other academic)
Keyword
Spinal motor neuron, fictive-locomotion
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-280052 (URN)
Funder
The Swedish Brain Foundation
Available from: 2016-03-07 Created: 2016-03-07 Last updated: 2016-04-12
4. HelioScan: A software framework for controlling in vivo microscopy setups with high hardware flexibility, functional diversity and extendibility
Open this publication in new window or tab >>HelioScan: A software framework for controlling in vivo microscopy setups with high hardware flexibility, functional diversity and extendibility
Show others...
2013 (English)In: Journal of Neuroscience Methods, ISSN 0165-0270, E-ISSN 1872-678X, Vol. 215, no 1, 38-52 p.Article in journal (Refereed) Published
Abstract [en]

Intravital microscopy such as in vivo imaging of brain dynamics is often performed with custom-built microscope setups controlled by custom-written software to meet specific requirements. Continuous technological advancement in the field has created a need for new control software that is flexible enough to support the biological researcher with innovative imaging techniques and provide the developer with a solid platform for quickly and easily implementing new extensions. Here, we introduce HelioScan, a software package written in LabVIEW, as a platform serving this dual role. HelioScan is designed as a collection of components that can be flexibly assembled into microscope control software tailored to the particular hardware and functionality requirements. Moreover, HelioScan provides a software framework, within which new functionality can be implemented in a quick and structured manner. A specific HelioScan application assembles at run-time from individual software components, based on user-definable configuration files. Due to its component-based architecture, HelioScan can exploit synergies of multiple developers working in parallel on different components in a community effort. We exemplify the capabilities and versatility of HelioScan by demonstrating several in vivo brain imaging modes, including camera-based intrinsic optical signal imaging for functional mapping of cortical areas, standard two-photon laser-scanning microscopy using galvanometric mirrors, and high-speed in vivo two-photon calcium imaging using either acousto-optic deflectors or a resonant scanner. We recommend HelioScan as a convenient software framework for the in vivo imaging community.

Keyword
Two-photon laser scanning microscopy, Intrinsic optical imaging, Control software, LabVIEW
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-201813 (URN)10.1016/j.jneumeth.2013.02.006 (DOI)000318828100005 ()
Note

Paid Open Access

Available from: 2013-06-17 Created: 2013-06-17 Last updated: 2017-05-04Bibliographically approved

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