کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5737362 1614714 2017 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Hyperexcitability in synaptic and firing activities of spinal motoneurons in an adult mouse model of amyotrophic lateral sclerosis
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Hyperexcitability in synaptic and firing activities of spinal motoneurons in an adult mouse model of amyotrophic lateral sclerosis
چکیده انگلیسی


- Hyperexcitability was observed in motor outputs due to diminished sSTD in the spinal motor system of mSOD1G93A mice.
- Spinal network- and NMDAR-dependent oEPSPs were first observed and were hyperactive in mSOD1G93A MNs.
- Fast EPSPs were found to be similar between mSOD1G93A MNs and NT MNs at P50-90.

Hyperexcitability is hypothesized to contribute to the degeneration of spinal motoneurons (MNs) in amyotrophic lateral sclerosis (ALS). Studies, thus far, have not linked hyperexcitability to the intrinsic properties of MNs in the adult ALS mouse model with the G93A-mutated SOD1 protein (mSOD1G93A). In this study, we obtained two types of measurements: ventral root recordings to assess motor output and intracellular recordings to assess synaptic properties of individual MNs. All studies were carried out in an in vitro preparation of the sacral spinal cords of mSOD1G93A mice and their non-transgenic (NT) littermates, both in the age range of 50-90 days. Ventral root recordings revealed that maximum compound action potentials (coAPs) evoked by a short-train stimulation of corresponding dorsal roots were similar between the two types of mice. Although the progressive depression of coAPs was present during the train stimulation in all recordings, the coAP depression in mSOD1G93A mice was to a lesser extent, which suggests an increased firing tendency in mSOD1G93A MNs. Intracellular recordings showed no changes in fast excitatory postsynaptic potentials (EPSPs) in mSOD1G93A MNs. However, recording did show that oscillating EPSPs (oEPSPs) were induced by poly-EPSPs at a higher frequency and by less-intense electrical stimulation in mSOD1G93A MNs. These oEPSPs were dependent upon the activities of spinal network and N-methyl-d-aspartate receptors (NMDARs), and were subjected to riluzole modulation. Taken together, these findings revealed abnormal electrophysiology in mSOD1G93A MNs that could underlie ALS excitotoxicity.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 362, 24 October 2017, Pages 33-46
نویسندگان
, , , ,