Activation of Early Silent Synapses by Spontaneous Synchronous Network Activity Limits the Range of Neocortical Connections

• Published in: The Journal of neuroscience 2005-05, Vol.25 (18), p.4605-4615
• Main Authors: Voigt, Thomas, Opitz, Thoralf, de Lima, Ana Dolabela
• Format: Article
• Language: English
• Subjects: 2-Amino-5-phosphonovalerate - pharmacology; 6-Cyano-7-nitroquinoxaline-2,3-dione - pharmacology; Animals; Axons - drug effects; Bicuculline - analogs & derivatives; Bicuculline - pharmacology; Calcium Signaling - drug effects; Calcium Signaling - physiology; Development/Plasticity/Repair; Dextrans - metabolism; Electric Stimulation - methods; Embryo, Mammalian; Excitatory Amino Acid Antagonists - pharmacology; GABA Antagonists - pharmacology; Immunohistochemistry - methods; Membrane Potentials - drug effects; Membrane Potentials - physiology; Membrane Potentials - radiation effects; Neocortex - cytology; Nerve Net - cytology; Nerve Net - embryology; Nerve Net - physiology; Neural Pathways - cytology; Neural Pathways - physiology; Patch-Clamp Techniques - methods; Rats; Rats, Sprague-Dawley; Receptors, AMPA - metabolism; Receptors, N-Methyl-D-Aspartate - metabolism; Rhodamines - metabolism; Synapses - physiology; Synaptophysin - metabolism; Time Factors
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.3803-04.2005

During the early development of neocortical networks, many glutamatergic synapses lack AMPA receptors and are physiologically silent. We show in neocortical cultures that spontaneous synchronous network activity is able to convert silent synapses to active synapses by the incorporation of AMPA receptors into synaptic complexes throughout the network within a few minutes. To test the effect of synaptic activation on the connectivity of neuronal populations, we created separated neuronal networks that could innervate each other. We allowed outgrowing axons to invade the neighboring network either before or after the onset of synchronous network activity. In the first case, both subnetworks connected to each other and synchronized their activity, whereas in the second case, axonal connections failed to form and network activity did not synchronize between compartments. We conclude that early spontaneous synchronous network activity triggers a global AMPAfication of immature synapses, which in turn prevents later-arriving axons from forming afferent connections. This activity-dependent process may set the range of corticocortical connections during early network development before experience-dependent mechanisms begin elaborating the mature layout of the neocortical connections and modules.