An ex vivo preparation of mature mice spinal cord to study synaptic transmission on motoneurons

Moghaddasi, Mehrnoush; Velumian, Alexander A.; Zhang, Liang; Fehlings, Michael G.

doi:10.1016/j.jneumeth.2006.06.009

Cited by 13 publications

(7 citation statements)

References 40 publications

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“…The stimulus–response relationship showed that the maximum SR was mostly reached at an intensity of 2 times threshold with a slight, further increase up to 5–10 times threshold intensity, as illustrated in Figure 1, A and C . The latency for the SR was stable and short (~2 ms) in both NT and mSOD1 mice, and therefore it is likely mediated through monosynaptic transmission, as reported by two other laboratories (Li et al, 2004; Moghaddasi et al, 2007). This was further supported by jitter analysis (Doyle and Andresen, 2001), which showed little variability in the SR latency (stimulation, mean latency ± SD: 1.5 times threshold, 2.43 ms ±10 μ s; 5 times threshold, 2.34 ms ±20 μ s; n =4 mice).…”

Section: Resultssupporting

confidence: 64%

Progressive Changes in Synaptic Inputs to Motoneurons in Adult Sacral Spinal Cord of a Mouse Model of Amyotrophic Lateral Sclerosis

Jiang

Schuster²,

Fu³

et al. 2009

J. Neurosci.

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Amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of motoneurons. One potential mechanism is excitotoxicity. We studied the behaviors of spinal neurons using an in vitro preparation of the sacral cord from the G93A SOD1 mouse model of ALS. Measurements were conducted at presymptomatic [approximately postnatal day 50 (ϳP50)], early (ϳP90), and late (ϾP120) stages of the disease. Short-latency reflexes (SRs) in ventral roots, presumably monosynaptic, were evoked by electrical stimulation of a dorsal root. The fraction of motoneurons capable of responding to this activation was evaluated by measuring the compound action potential [total motor activity (TMA)] evoked by antidromic stimulation of the distal ventral root. In mutant SOD1 (mSOD1) mice, both the SR and the TMA decreased with age compared with nontransgenic littermates, ruling out the SR as a source of increasing excitotoxicity. Spinal interneuron activity was assessed using the synchronized ventral root bursts generated by both bath application of blockers of inhibitory neurotransmitters (glycine, GABA A ) and agonists of glutamate receptors (especially NMDA receptors). After symptom onset, a higher percentage of preparations from mSOD1 mice exhibited bursting, and these bursts exhibited more sub-bursts and a more disorganized pattern. In mSOD1 mice with clear muscle tremor, the ventral roots exhibited spontaneous synchronized bursts, which were highly sensitive to the blockade of NMDA receptors. These data suggest that although short-latency sensory input does not increase as symptoms develop, interneuron activity does increase and may contribute to excitotoxicity.

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Section: Resultssupporting

confidence: 64%

Progressive Changes in Synaptic Inputs to Motoneurons in Adult Sacral Spinal Cord of a Mouse Model of Amyotrophic Lateral Sclerosis

Jiang

Schuster²,

Fu³

et al. 2009

J. Neurosci.

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“…3L-S). These findings identify an extreme SSC instability as a major component of adult MN vulnerability in response to slicing procedures, most likely because of their large dendritic arbor (41).…”

Section: Mn Activity and Cholinergic Stimulation Affects Size And Intmentioning

confidence: 80%

Localization and dynamic changes of neuregulin‐1 at C‐type synaptic boutons in association with motor neuron injury and repair

et al. 2019

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C‐type synaptic boutons (C‐boutons) provide cholinergic afferent input to spinal cord motor neurons (MNs), which display an endoplasmic reticulum (ER)–related subsurface cistern (SSC) adjacent to their postsynaptic membrane. A constellation of postsynaptic proteins is clustered at C‐boutons, including M2 muscarinic receptors, potassium channels, and σ‐1 receptors. In addition, we previously found that neuregulin (NRG)1 is associated with C‐boutons at postsynaptic SSCs, whereas its ErbB receptors are located in the presynaptic compartment. C‐bouton–mediated regulation of MN excitability has been implicated in MN disease, but NRG1‐mediated functions and the impact of various pathologic conditions on C‐bouton integrity have not been studied in detail. Here, we investigated changes in C‐boutons after electrical stimulation, pharmacological treatment, and peripheral nerve axotomy. SSC‐linked NRG1 clusters were severely disrupted in acutely stressed MNs and after tunicamycin‐induced ER stress. In axotomized MNs, C‐bouton loss occurred in concomitance with microglial recruitment and was prevented by the ER stress inhibitor salubrinal. Activated microglia displayed a positive chemotaxis to C‐boutons. Analysis of transgenic mice overexpressing NRG1 type I and type III isoforms in MNs indicated that NRG1 type III acts as an organizer of SSC‐like structures, whereas NRG1 type I promotes synaptogenesis of presynaptic cholinergic terminals. Moreover, MN‐derived NRG1 signals may regulate the activity of perineuronal microglial cells. Together, these data provide new insights into the molecular and cellular pathology of C‐boutons in MN injury and suggest that distinct NRG1 isoform–mediated signaling functions regulate the complex matching between pre‐ and postsynaptic C‐bouton elements.—Salvany, S., Casanovas, A., Tarabal, O., Piedrafita, L., Hernández, S., Santafé, M., Soto‐Bernardini, M. C., Calderó, J., Schwab, M. H., Esquerda, J. E. Localization and dynamic changes of neuregulin‐1 at C‐type synaptic boutons in association with motor neuron injury and repair. FASEB J. 33, 7833–7851 (2019). http://www.fasebj.org

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“…The animals were anesthetized by halothane/N 2 O inhalation followed by intraperitoneal injection of pentobarbital (60 mg/kg). The animals were decapitated, the spine from the upper cervical to lower lumbar levels was quickly removed, and the spinal cord was hydraulically extruded as described in detail elsewhere (Chery et al 2000;Moghaddasi et al 2007;Velumian et al 2010). The whole procedure from decapitation to extruding the spinal cord typically took 1.5-2 min.…”

Section: Spinal Cord White Matter Preparationmentioning

confidence: 99%

Contribution of Fast and Slow Conducting Myelinated Axons to Single-Peak Compound Action Potentials in Rat Spinal Cord White Matter Preparations

Velumian¹,

Wan²,

Samoilova

et al. 2011

Journal of Neurophysiology

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Unlike recordings derived from optic nerve or corpus callosum, compound action potentials (CAPs) recorded from rodent spinal cord white matter (WM) have a characteristic single-peak shape despite the heterogeneity of axonal populations. Using a double sucrose gap technique, we analyzed the CAPs recorded from dorsal, lateral, and ventral WM from mature rat spinal cord. The CAP decay was significantly prolonged with increasing stimulus intensities suggesting a recruitment of higher threshold, slower conducting axons. At 3.5 mm conduction distance, a hidden higher threshold, slower conducting component responsible for prolongation of CAP decay was uncovered in 22 of 25 of dorsal WM strips by analyzing the stimulus-response relationships and a normalization-subtraction procedure. This component had a peak conduction velocity (CV) of 5.0 ± 0.2 (SE) m/s as compared with 9.3 ± 0.5 m/s for the lower threshold peak (P < 0.0001). Oxygen-glucose deprivation (OGD), along with its known effects on CAP amplitude, significantly (P < 0.015) shortened the CAP decay. The hidden higher threshold, slower conducting component showed greater sensitivity to OGD compared with the lower threshold, faster conducting component, suggesting a differential sensitivity of axonal populations of spinal cord WM. At longer conduction distances and lower temperatures (9.8 mm, 22-24°C), the slower peak could be directly visualized in CAPs at higher stimulation intensities. A detailed analysis of single-peak CAPs to identify their fast and slow conducting components may be of particular importance for studies of axonal physiology and pathophysiology in small animals where the conduction distance is not sufficiently long to separate the CAP peaks.

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An ex vivo preparation of mature mice spinal cord to study synaptic transmission on motoneurons

Cited by 13 publications

References 40 publications

Progressive Changes in Synaptic Inputs to Motoneurons in Adult Sacral Spinal Cord of a Mouse Model of Amyotrophic Lateral Sclerosis

Progressive Changes in Synaptic Inputs to Motoneurons in Adult Sacral Spinal Cord of a Mouse Model of Amyotrophic Lateral Sclerosis

Localization and dynamic changes of neuregulin‐1 at C‐type synaptic boutons in association with motor neuron injury and repair

Contribution of Fast and Slow Conducting Myelinated Axons to Single-Peak Compound Action Potentials in Rat Spinal Cord White Matter Preparations

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