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Altered development in GABA co-release shapes glycinergic synaptic currents in cultured spinal slices of the SOD1G93A mouse model of ALS

Medelin, M; Rancic, V; Cellot, G; Laishram, J; Veeraraghavan, P; Rossi, C; Muzio, L; ... Ballerini, L; + view all (2016) Altered development in GABA co-release shapes glycinergic synaptic currents in cultured spinal slices of the SOD1G93A mouse model of ALS. The Journal of Physiology , 594 (13) pp. 3827-3840. 10.1113/JP272382. Green open access

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Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal, adult-onset neurological disease characterized by progressive degeneration of motoneurons (MNs). In our previous study we developed organotypic spinal cultures from an ALS mouse model expressing a mutant form of human superoxide dismutase 1 (SOD1G93A ). We reported the presence of a significant synaptic rearrangement expressed by these embryonic cultured networks, which may lead to altered development of spinal synaptic signalling, potentially linked to the adult disease phenotype. Recent studies on the same ALS mouse model, reported a selective loss of glycinergic innervation in cultured MNs, suggestive of a contribution of synaptic inhibition to MNs dysfunction and degeneration. Here we further exploit organotypic cultures from wild type and SOD1G93A mice to investigate the development of glycine-receptor mediated synaptic currents recorded from interneurons of the premotor ventral circuits. We perform single cell electrophysiology, immunocytochemistry and confocal microscopy and we suggest that GABA co-release may speed the decay of glycine responses altering, in SOD1G93A developing networks, temporal precision and signal integration at the postsynaptic site. Our hypothesis is supported by the finding of an increased MN bursting activity in immature SOD1G93A spinal cords and by immunofluorescence microscopy detection of longer persistence of GABA in SOD1G93A glycinergic terminals in cultured and ex-vivo spinal slices.

Type: Article
Title: Altered development in GABA co-release shapes glycinergic synaptic currents in cultured spinal slices of the SOD1G93A mouse model of ALS
Location: UK
Open access status: An open access version is available from UCL Discovery
DOI: 10.1113/JP272382
Publisher version: http://dx.doi.org/10.1113/JP272382
Language: English
Additional information: This is the peer reviewed version of the following article: Medelin, M; Rancic, V; Cellot, G; Laishram, J; Veeraraghavan, P; Rossi, C; Muzio, L; (2016) Altered development in GABA co-release shapes glycinergic synaptic currents in cultured spinal slices of the SOD1G93A mouse model of ALS. The Journal of Physiology, which has been published in final form at: http://dx.doi.org/10.1113/JP272382. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving (http://olabout.wiley.com/WileyCDA/Section/id-828039.html#terms).
Keywords: organotypic cultures, glycinergic currents, spinal interneurones, neurodegenerative disease
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: http://discovery.ucl.ac.uk/id/eprint/1478101
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