Progressive changes in synaptic inputs to motoneurons in adult sacral spinal cord of a mouse model of amyotrophic lateral sclerosis

Mingchen Jiang*, Jenna E. Schuster, Ronggen Fu, Teepu Siddique, C. J. Heckman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of motoneurons. One potential mechanism is excitotoxicity. Westudied 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 (∼P50)], early (∼P90), and late (>P120) 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, GABAA) 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.

Original languageEnglish (US)
Pages (from-to)15031-15038
Number of pages8
JournalJournal of Neuroscience
Volume29
Issue number48
DOIs
StatePublished - Dec 2 2009

ASJC Scopus subject areas

  • Neuroscience(all)

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