Developmental Disruption of Recurrent Inhibitory Feedback Results in Compensatory Adaptation in the Renshaw Cell–Motor Neuron Circuit

Enjin, Anders; Perry, Sharn; Hilscher, Markus M.; Nagaraja, Chetan; Larhammar, Martin; Gezelius, Henrik; Eriksson, Anders; Leão, Katarina E.; Kullander, Klas

doi:10.1523/jneurosci.0949-16.2017

Cited by 21 publications

(15 citation statements)

References 54 publications

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“…It was originally used to detect neuromuscular injury and skeletal muscle dystrophy 41,42 . It was later used to assess damage to the corticospinal tract after spinal cord injury 43,44 , but the grip test has not been used to assess WMI-induced motor function after ICH. Our results showed that changes in muscle strength were significantly associated with changes in the latency of MEPs.…”

Section: Discussionmentioning

confidence: 99%

Modified behavioural tests to detect white matter injury- induced motor deficits after intracerebral haemorrhage in mice

Chen

Xia

Guo

et al. 2019

Sci Rep

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Motor function deficit induced by white matter injury (WMI) is one of the most severe complications of intracerebral haemorrhage (ICH). The degree of WMI is closely related to the prognosis of patients after ICH. However, the current behavioural assessment of motor function used in the ICH mouse model is mainly based on that for ischaemic stroke and lacks the behavioural methods that accurately respond to WMI. Here, a series of easy-to-implement behavioural tests were performed to detect motor deficits in mice after ICH. The results showed that the grip strength test and the modified pole test not only can better distinguish the degree of motor dysfunction between different volumes of blood ICH models than the Basso Mouse Scale and the beam walking test but can also accurately reflect the severity of WMI characterized by demyelination, axonal swelling and the latency of motor-evoked potential delay induced by ICH. In addition, after ICH, the results of grip tests and modified pole tests, rather than the Basso Mouse Scale and the beam walking test, were worse than those observed after intraventricular haemorrhage (IVH), which was used as a model of brain haemorrhage in non-white matter areas. These results indicate that the grip strength test and the modified pole test have advantages in detecting the degree of motor deficit induced by white matter injury after ICH in mice.

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Section: Discussionmentioning

confidence: 99%

Modified behavioural tests to detect white matter injury- induced motor deficits after intracerebral haemorrhage in mice

Chen

Xia

Guo

et al. 2019

Sci Rep

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“…For this reason, several recent studies have made use of highly purified MN preparations for pharmacology and studies of disease-state excitability ( Ullian et al, 2004 ; Barthélémy-Requin et al, 2006 ; Beaudet et al, 2015 ; Sances et al, 2016 ). However, interneurons within the spinal cord provide important, recurrent inhibitory feedback to the MNs and some studies suggest that Renshaw cells have an integral role in movement, though their role is yet to be fully elucidated ( Alvarez and Fyffe, 2007 ; Enjin et al, 2017 ). Additionally, our culture was largely comprised of non-neuronal support cells (likely a combination of astrocytes and Schwann cells).…”

Section: Discussionmentioning

confidence: 99%

Spontaneous and Evoked Activity from Murine Ventral Horn Cultures on Microelectrode Arrays

Black

Atmaramani

Pancrazio

2017

Front. Cell. Neurosci.

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Motor neurons are the site of action for several neurological disorders and paralytic toxins, with cell bodies located in the ventral horn (VH) of the spinal cord along with interneurons and support cells. Microelectrode arrays (MEAs) have emerged as a high content assay platform for mechanistic studies and drug discovery. Here, we explored the spontaneous and evoked electrical activity of VH cultures derived from embryonic mouse spinal cord on multi-well plates of MEAs. Primary VH cultures from embryonic day 15–16 mice were characterized by expression of choline acetyltransferase (ChAT) by immunocytochemistry. Well resolved, all-or-nothing spontaneous spikes with profiles consistent with extracellular action potentials were observed after 3 days in vitro, persisting with consistent firing rates until at least day in vitro 19. The majority of the spontaneous activity consisted of tonic firing interspersed with coordinated bursting across the network. After 5 days in vitro, spike activity was readily evoked by voltage pulses where a minimum amplitude and duration required for excitation was 300 mV and 100 μs/phase, respectively. We characterized the sensitivity of spontaneous and evoked activity to a host of pharmacological agents including AP5, CNQX, strychnine, ω-agatoxin IVA, and botulinum neurotoxin serotype A (BoNT/A). These experiments revealed sensitivity of the cultured VH to both agonist and antagonist compounds in a manner consistent with mature tissue derived from slices. In the case of BoNT/A, we also demonstrated intoxication persistence over an 18-day period, followed by partial intoxication recovery induced by N- and P/Q-type calcium channel agonist GV-58. In total, our findings suggest that VH cultures on multi-well MEA plates may represent a moderate throughput, high content assay for performing mechanistic studies and for screening potential therapeutics pertaining to paralytic toxins and neurological disorders.

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“…But evidence that supports layered processing in the spinal cord has been indirect, and results largely from studies of “errors” in stepping called deletions ( Dyck et al., 2012 , Griener et al., 2017 , Rybak et al., 2006 , Zhong et al., 2012 ). Another approach to examine layered processing in the spinal cord has been to quantify the changes in locomotor behavior when whole cardinal classes of genetically defined neurons are silenced or eliminated from spinal motor circuits ( Andersson et al., 2012 , Caldeira et al., 2017 , Crone et al., 2008 , Crone et al., 2009 , Dougherty et al., 2013 , Enjin et al., 2017 , Gosgnach et al., 2006 , Lanuza et al., 2004 , Talpalar et al., 2013 , Zhang et al., 2008 , Zhang et al., 2014 ). With these approaches, specific interneuronal classes have been assigned to different layers of processing: a rhythm-generating layer that projects to a pattern formation layer that in turn forms synaptic connections with motoneurons ( Dyck et al., 2012 , Griener et al., 2017 , Zhong et al., 2012 ).…”

Section: Introductionmentioning

confidence: 99%

Sub-populations of Spinal V3 Interneurons Form Focal Modules of Layered Pre-motor Microcircuits

et al. 2018

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SummaryLayering of neural circuits facilitates the separation of neurons with high spatial sensitivity from those that play integrative temporal roles. Although anatomical layers are readily identifiable in the brain, layering is not structurally obvious in the spinal cord. But computational studies of motor behaviors have led to the concept of layered processing in the spinal cord. It has been postulated that spinal V3 interneurons (INs) play multiple roles in locomotion, leading us to investigate whether they form layered microcircuits. Using patch-clamp recordings in combination with holographic glutamate uncaging, we demonstrate focal, layered modules, in which ventromedial V3 INs form synapses with one another and with ventrolateral V3 INs, which in turn form synapses with ipsilateral motoneurons. Motoneurons, in turn, provide recurrent excitatory, glutamatergic input to V3 INs. Thus, ventral V3 interneurons form layered microcircuits that could function to ensure well-timed, spatially specific movements.

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Developmental Disruption of Recurrent Inhibitory Feedback Results in Compensatory Adaptation in the Renshaw Cell–Motor Neuron Circuit

Cited by 21 publications

References 54 publications

Modified behavioural tests to detect white matter injury- induced motor deficits after intracerebral haemorrhage in mice

Modified behavioural tests to detect white matter injury- induced motor deficits after intracerebral haemorrhage in mice

Spontaneous and Evoked Activity from Murine Ventral Horn Cultures on Microelectrode Arrays

Sub-populations of Spinal V3 Interneurons Form Focal Modules of Layered Pre-motor Microcircuits

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