Differential control of thrombospondin over synaptic glycine and AMPA receptors in spinal cord neurons

• Published in: The Journal of neuroscience Vol. 33; no. 28; pp. 11432 - 11439
• Main Authors: Hennekinne, Laetitia, Colasse, Sabrina, Triller, Antoine, Renner, Marianne
• Format: Journal Article
• Language: English
• Published: United States Society for Neuroscience 10.07.2013
• Subjects: Animals; Cells, Cultured; Female; Male; Neurons - drug effects; Neurons - metabolism; Rats; Rats, Sprague-Dawley; Receptors, AMPA - antagonists & inhibitors; Receptors, AMPA - metabolism; Receptors, Glycine - agonists; Receptors, Glycine - metabolism; Spinal Cord - drug effects; Spinal Cord - metabolism; Synapses - drug effects; Synapses - metabolism; Thrombospondin 1 - physiology
• ISSN: 0270-6474; 1529-2401; 1529-2401
• DOI: 10.1523/jneurosci.5247-12.2013

Thrombospondin-1 (TSP-1) is a large extracellular matrix protein secreted by astrocytes during development and inflammation. In the developing CNS, TSP-1 is involved in neuronal migration and adhesion, neurite outgrowth, and synaptogenesis. We investigated the effects of TSP-1 on neurons with mature synapses using immunocytochemistry, single-particle tracking, surface biotinylation, and calcium imaging. We show that in cultured rat spinal cord neurons TSP-1 decreased neuronal excitability by reducing the accumulation of excitatory AMPA receptors (AMPARs) and increasing that of inhibitory glycine receptors (GlyRs) in synapses. The effects of TSP-1 on GlyRs were dependent on the activation of excitatory receptors. These changes were abolished by blocking β1-integrins and mimicked by blocking β3-integrins. In the presence of TSP-1, AMPARs were less stabilized at synapses, increasing their lateral diffusion and endocytosis. Interestingly, TSP-1 counteracted the increased neuronal excitability and neuronal death induced by TNFα. These results suggest a role of TSP-1 in controlling the balance between excitation and inhibition which could help the recovery of normal synaptic activity after injury responses.