Distinct development of the glycinergic terminals in the ventral and dorsal horns of the mouse cervical spinal cord

Sunagawa, Masanobu; Shimizu-Okabe, Chigusa; Kim, Jeong-Tae; Kobayashi, Shiori; Kosaka, Yoshinori; Yanagawa, Yuchio; Matsushita, Masayuki; Okabe, Akihito; Takayama, Chitoshi

doi:10.1016/j.neuroscience.2016.12.032

Cited by 15 publications

(32 citation statements)

References 62 publications

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“…While a proportion of spinal interneurons and autonomic preganglionic neurons can also be ChA+, they are more enriched in the dorsal half and/or thoracic and cervical sections of the spinal cord [41]. Also, these neurons differentiate and emerge at later embryonic stages, especially in the lumbar ventral horns (from E13.5; [42,43]), than those used in our experiments (E12.5).…”

Section: Immunocytochemical Techniquesmentioning

confidence: 61%

Neuromuscular Activity Induces Paracrine Signaling and Triggers Axonal Regrowth after Injury in Microfluidic Lab-On-Chip Devices

Sala-Jarque

Mesquida-Veny

Badiola-Mateos

et al. 2020

Cells

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Peripheral nerve injuries, including motor neuron axonal injury, often lead to functional impairments. Current therapies are mostly limited to surgical intervention after lesion, yet these interventions have limited success in restoring functionality. Current activity-based therapies after axonal injuries are based on trial-error approaches in which the details of the underlying cellular and molecular processes are largely unknown. Here we show the effects of the modulation of both neuronal and muscular activity with optogenetic approaches to assess the regenerative capacity of cultured motor neuron (MN) after lesion in a compartmentalized microfluidic-assisted axotomy device. With increased neuronal activity, we observed an increase in the ratio of regrowing axons after injury in our peripheral-injury model. Moreover, increasing muscular activity induces the liberation of leukemia inhibitory factor and glial cell line-derived neurotrophic factor in a paracrine fashion that in turn triggers axonal regrowth of lesioned MN in our 3D hydrogel cultures. The relevance of our findings as well as the novel approaches used in this study could be useful not only after axotomy events but also in diseases affecting MN survival.

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Section: Immunocytochemical Techniquesmentioning

confidence: 61%

Neuromuscular Activity Induces Paracrine Signaling and Triggers Axonal Regrowth after Injury in Microfluidic Lab-On-Chip Devices

Sala-Jarque

Mesquida-Veny

Badiola-Mateos

et al. 2020

Cells

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“…51 In addition, the electrophysiological properties of GABAergic neurons in the spinal cord could be changed during development. 22,[52][53][54][55] However, the primary inputs to GABAergic neurons in lamina II didn't display significant changes between young (P21) mice and adult (P49) mice. 56 GABAergic neurons of Gad67-EGFP mice has been comprehensively observed in other body regions which has been found highly expressed in the neocortical and hippocampal parts.…”

Section: Discussionmentioning

confidence: 98%

Spinal GABAergic neurons are under feed-forward inhibitory control driven by Aδ and C fibers in Gad2 td-Tomato mice

Liu

Zhang

et al. 2021

Mol Pain

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Background Spinal GABAergic neurons act as a critical modulator in sensory transmission like pain or itch. The monosynaptic or polysynaptic primary afferent inputs onto GABAergic neurons, along with other interneurons or projection neurons make up the direct and feed-forward inhibitory neural circuits. Previous research indicates that spinal GABAergic neurons mainly receive excitatory inputs from Aδ and C fibers. However, whether they are controlled by other inhibitory sending signals is not well understood. Methods We applied a transgenic mouse line in which neurons co-expressed the GABA-synthesizing enzyme Gad65 and the enhanced red fluorescence (td-Tomato) to characterize the features of morphology and electrophysiology of GABAergic neurons. Patch-clamp whole cell recordings were used to record the evoked postsynaptic potentials of fluorescent neurons in spinal slices in response to dorsal root stimulation. Results We demonstrated that GABAergic neurons not only received excitatory drive from peripheral Aβ, Aδ and C fibers, but also received inhibitory inputs driven by Aδ and C fibers. The evoked inhibitory postsynaptic potentials (eIPSPs) mediated by C fibers were mainly Glycinergic (66.7%) as well as GABAergic mixed with Glycinergic (33.3%), whereas the inhibition mediated by Aδ fibers was predominately both GABA and Glycine-dominant (57.1%), and the rest of which was purely Glycine-dominant (42.9%). Conclusion These results indicated that spinal GABAergic inhibitory neurons are under feedforward inhibitory control driven by primary C and Aδ fibers, suggesting that this feed-forward inhibitory pathway may play an important role in balancing the excitability of GABAergic neurons in spinal dorsal horn.

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“…Two possibilities could be considered regarding the GAD65/67-negative cell; one is that the cell was pure glycinergic, and the other is that the cell was excitatory. A recent immunohistochemical study showed that in neonatal mice, GLYT2 and GAD are often colocalized in the same terminals in the ventral horn of the spinal cord; during the second postnatal week, GABAergic terminals markedly decreased and glycinergic terminals became dominant ( Sunagawa et al, 2017 ). Although terminals that were GLYT2-positive but GAD-negative were sparse at postnatal day 0 ( Sunagawa et al, 2017 ), it is still possible that the GAD65/67-negative cell observed in the present study was pure glycinergic.…”

Section: Discussionmentioning

confidence: 99%

“…A recent immunohistochemical study showed that in neonatal mice, GLYT2 and GAD are often colocalized in the same terminals in the ventral horn of the spinal cord; during the second postnatal week, GABAergic terminals markedly decreased and glycinergic terminals became dominant ( Sunagawa et al, 2017 ). Although terminals that were GLYT2-positive but GAD-negative were sparse at postnatal day 0 ( Sunagawa et al, 2017 ), it is still possible that the GAD65/67-negative cell observed in the present study was pure glycinergic. Related to the possibility that the GAD65/67-negative cell was excitatory, some studies suggest that there are recurrent excitatory pathways from the recurrent collaterals of motoneurons ( Machacek and Hochman, 2006 ; Bonnot et al, 2009 ).…”

Section: Discussionmentioning

confidence: 99%

Expressions of VGLUT1/2 in the inspiratory interneurons and GAD65/67 in the inspiratory Renshaw cells in the neonatal rat upper thoracic spinal cord

et al. 2018

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HighlightsAbout half of the inspiratory interneurons in the ventromedial area of the third thoracic segment are glutamatergic.These glutamatergic interneurons may enhance the inspiratory intercostal motor activity.Inspiratory Renshaw cells exist in the ventromedial area of the third thoracic segments.Most of these Renshaw cells are GABAergic, and cause a single spike followed by ventral root stimulation at neonatal stage.

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Distinct development of the glycinergic terminals in the ventral and dorsal horns of the mouse cervical spinal cord

Cited by 15 publications

References 62 publications

Neuromuscular Activity Induces Paracrine Signaling and Triggers Axonal Regrowth after Injury in Microfluidic Lab-On-Chip Devices

Neuromuscular Activity Induces Paracrine Signaling and Triggers Axonal Regrowth after Injury in Microfluidic Lab-On-Chip Devices

Spinal GABAergic neurons are under feed-forward inhibitory control driven by Aδ and C fibers in Gad2 td-Tomato mice

Expressions of VGLUT1/2 in the inspiratory interneurons and GAD65/67 in the inspiratory Renshaw cells in the neonatal rat upper thoracic spinal cord

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