title: Spinal inhibitory circuits and their role in motor neuron degeneration.
abstract: In the spinal cord neuronal activity is controlled by the balance between excitatory and inhibitory neurotransmission, mediated mainly by the neurotransmitters glutamate and GABA/glycine, respectively. Alterations of this equilibrium have been associated with spinal motor neuron hyperexcitability and degeneration, which can be induced by excitotoxicity or by decreasing inhibitory neurotransmission. Here we review the ventral horn neuronal network and the possible involvement of inhibitory circuits in the mechanisms of degeneration of motor neurons characteristic of amyotrophic lateral sclerosis (ALS). Whereas glutamate mediated excitotoxicity seems to be an important factor, recent experimental and histopathological evidence argue in favor of a decreased activity of the inhibitory circuits controlling motor neuron excitability, mainly the recurrent inhibition exerted by Renshaw cells. A decreased Renshaw cell activity may be caused by cell loss or by a reduction of its inhibitory action secondary to a decreased excitation from cholinergic interneurons. Ultimately, inhibitory failure by either mechanism might lead to motor neuron degeneration, and this suggests inhibitory circuits and Renshaw cells as pharmacologic targets for ALS treatment.
authors.affiliation: División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 México, D. F., Mexico.
authors.forename: Uri Nimrod
authors.initials: UN
authors.lastname: Ramírez-Jarquín
authors.affiliation: División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 México, D. F., Mexico.
authors.forename: Rafael
authors.initials: R
authors.lastname: Lazo-Gómez
authors.affiliation: División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 México, D. F., Mexico.
authors.forename: Luis B
authors.initials: LB
authors.lastname: Tovar-Y-Romo
authors.affiliation: División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 México, D. F., Mexico. Electronic address: rtapia@ifc.unam.mx.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Tapia
mesh_terms: D000818:Animals; D000870:Anterior Horn Cells / Q000502:physiology; D006801:Humans; D016472:Motor Neuron Disease / Q000503:physiopathology*; D009046:Motor Neurons / Q000502:physiology*; D009410:Nerve Degeneration / Q000503:physiopathology*; D009433:Neural Inhibition / Q000502:physiology*; D066293:Renshaw Cells / Q000502:physiology; D013116:Spinal Cord / Q000503:physiopathology*
keywords: Acetylcholine; Amyotrophic lateral sclerosis; GABA; Glycine; Inhibitory circuits; Renshaw cell; Spinal motor neuron degeneration