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| 2. |
- Enjin, Anders, et al.
(författare)
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Developmental disruption of recurrent inhibitory feedback results in compensatory adaptation in the Renshaw cell-motor neuron circuit
- 2017
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 37:23, s. 5634-5647
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Tidskriftsartikel (refereegranskat)abstract
- When activating muscles, motor neurons in the spinal cord also activate Renshaw cells, which provide recurrent inhibitory feedback to the motor neurons. The tight coupling with motor neurons suggests that Renshaw cells have an integral role in movement, a role that is yet to be elucidated. Here we used the selective expression of the nicotinic cholinergic receptor α2 (Chrna2) in mice to genetically target the vesicular inhibitory amino acid transporter (VIAAT) in Renshaw cells. Loss of VIAAT from Chrna2Cre-expressing Renshaw cells did not impact any aspect of drug-induced fictive locomotion in the neonatal mouse or change gait, motor coordination, or grip strength in adult mice of both sexes. However, motor neurons from neonatal mice lacking VIAAT in Renshaw cells received spontaneous inhibitory synaptic input with a reduced frequency, showed lower input resistance, and had an increased number of proprioceptive glutamatergic and calbindin-labeled putative Renshaw cell synapses on their soma and proximal dendrites. Concomitantly, Renshaw cells developed with increased excitability and a normal number of cholinergic motor neuron synapses, indicating a compensatory mechanism within the recurrent inhibitory feedback circuit. Our data suggest an integral role for Renshaw cell signaling in shaping the excitability and synaptic input to motor neurons.
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| 3. |
- Gezelius, Henrik, 1977-, et al.
(författare)
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Conditional genetic labeling of the Renshaw cell population for functional studies of motor control
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The Renshaw cells were among the first interneurons to be characterized in the mammalian spinal cord. Although the basic function of recurrent inhibition to motor neurons, as well as the Renshaw cell connectivity to other neurons have been thoroughly studied, the exact functional role of the Renshaw cells in motor control is still unknown. To further characterize the role of Renshaw cells in spinal cord circuitry, we searched for candidate genes useful in the Cre-loxP system. It has been reported that the mRNA expression of nicotinic cholinergic receptor alpha 2 (Chrna2) is found in a restricted number of cells at the ventral rim in adult rat and mouse spinal cord. In our own search for genes with distinct ventral expression, we noted a similar restricted Chrna2 mRNA expression pattern in the mouse spinal cord at postnatal day (P) 11 and during development at embryonic day 14.5. Based on the fact that the gene product is a cholinergic receptor and the pattern of expression, the neurons are predicted to be Renshaw cells. The possibility that these cells were motor neurons was excluded, since Chrna2 and Vesicular acetylcholine were not co-expressed at P11. To further study this cell population, we have generated a transgenic mouse expressing Cre recombinase (Cre) under the control of the Chrna2 promoter region. To visualize the Cre-expressing cells, the Chrna2-Cre transgenic mouse were bred with a reporter mouse expressing β-galactosidase (β-gal) in the nucleus after loxP excision. As expected, spinal cord β-gal immunoreactivity was observed in a limited number of ventrally located cells in the Cre-bearing offspring. Co-labeling of β-gal with calbindin-28K, a known marker for Renshaw cells, indicated that a majority of the calbindin positive cells were also β-gal positive at the ventral rim where calbindin is specific. In addition, β-gal positive cells without observable calbindin were also detected. It is conceivable that Chrna2 is expressed in additional cells apart from Renshaw cells or that a previously unidentified Renshaw cell subpopulation does not express calbindin. Nonetheless, a mouse with Cre-activity restricted to Chrna2-expressing cells opens the possibility to functionally study a limited population of spinal cord interneurons through genetic techniques, with the ambition to explore the specific role of Renshaw cells in spinal cord circuitry and motor control.
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| 4. |
- Langer, Dominik, et al.
(författare)
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HelioScan : A software framework for controlling in vivo microscopy setups with high hardware flexibility, functional diversity and extendibility
- 2013
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Ingår i: Journal of Neuroscience Methods. - : Elsevier BV. - 0165-0270 .- 1872-678X. ; 215:1, s. 38-52
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 8. |
- Nagaraja, Chetan, 1983-
(författare)
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Functional Imaging of Spinal Locomotor Networks
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 9. |
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| 10. |
- Perry, Sharn, et al.
(författare)
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Characterization of Dmrt3-Derived Neurons Suggest a Role within Locomotor Circuits
- 2019
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Ingår i: Journal of Neuroscience. - : SOC NEUROSCIENCE. - 0270-6474 .- 1529-2401. ; 39:10, s. 1771-1782
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Tidskriftsartikel (refereegranskat)abstract
- Neuronal networks within the spinal cord, collectively known as the central pattern generator (CPG), coordinate rhythmic movements underlying locomotion. The transcription factor doublesex and mab-3-related transcription factor 3 (DMRT3) is involved in the differentiation of the dorsal interneuron 6 class of spinal cord interneurons. In horses, a non-sense mutation in the Dmrt3 gene has major effects on gaiting ability, whereas mice lacking the Dmrt3 gene display impaired locomotor activity. Although the Dmrt3 gene is necessary for normal spinal network formation and function in mice, a direct role for Dmrt3-derived neurons in locomotor-related activities has not been demonstrated. Here we present the characteristics of the Dmrt3-derived spinal cord interneurons. Using transgenic mice of both sexes, we characterized interneurons labeled by their expression of Cre driven by the endogenous Dmrt3 promoter. We used molecular, retrograde tracing and electrophysiological techniques to examine the anatomical, morphological, and electrical properties of the Dmrt3-Cre neurons. We demonstrate that inhibitory Dmrt3-Cre neurons receive extensive synaptic inputs, innervate surrounding CPG neurons, intrinsically regulate CPG neuron's electrical activity, and are rhythmically active during fictive locomotion, bursting at frequencies independent to the ventral root output. The present study provides novel insights on the character of spinal Dmrt3-derived neurons, data demonstrating that these neurons participate in locomotor coordination.
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| 11. |
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| 12. |
- Rogoz, Katarzyna, et al.
(författare)
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Identification of a Neuronal Receptor Controlling Anaphylaxis
- 2016
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 14:2, s. 370-379
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Tidskriftsartikel (refereegranskat)abstract
- Allergic reactions can in severe cases induce a state of circulatory shock referred to as anaphylaxis. Histamine, the primary mediator of this condition, is released from immune cells, and, therefore, anaphylaxis has so far been considered an immune system disorder. However, we here show that the glutamatergic receptor mGluR7, expressed on a subpopulation of both peripheral and spinal cord neurons, controls histamine-induced communication through calcium-dependent autoinhibition with implications for anaphylaxis. Genetic ablation of mGluR7, and thus altered regulation of histamine-sensing neurons, caused an anaphylaxis-like state in mGluR7(-/-) mice, which could be reversed by antagonizing signaling between neurons and mast cells but not by antagonizing a central itch pathway. Our findings demonstrate the vital role of nervous system control by mGluR7 in anaphylaxis and open up possibilities for preventive strategies for this life-threatening condition.
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