Silent Synapses in the Developing Hippocampus: Lack of Functional AMPA Receptors or Low Probability of Glutamate Release?

• Published in: Proceedings of the National Academy of Sciences - PNAS 2000-08, Vol.97 (17), p.9741-9746
• Main Authors: Gasparini, Sonia, Saviane, Chiara, Voronin, Leon L., Cherubini, Enrico
• Format: Article
• Language: English
• Subjects: 6-Cyano-7-nitroquinoxaline-2,3-dione - pharmacology; AMPA receptors; Animals; Animals, Newborn; Benzothiadiazines - pharmacology; Biological Sciences; Biology; Brain; Electric Stimulation; Excitatory Amino Acid Antagonists - pharmacology; Excitatory Postsynaptic Potentials - physiology; Glutamic Acid - metabolism; Hippocampus; In Vitro Techniques; Long term potentiation; Membrane potential; Mossy Fibers, Hippocampal - drug effects; Mossy Fibers, Hippocampal - growth & development; Mossy Fibers, Hippocampal - metabolism; Mossy Fibers, Hippocampal - physiology; Neurology; Neurons; Neuroscience; Neurotransmitters; Physical growth; Piperazines - pharmacology; Postnatal development; Probability; Rats; Rats, Wistar; Receptors; Receptors, AMPA - antagonists & inhibitors; Receptors, AMPA - metabolism; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - metabolism; Synapses; Synaptic Transmission - drug effects; Temperature
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.170032297

At early developmental stages, silent synapses have been commonly found in different brain areas. These synapses are called silent because they do not respond at rest but are functional at positive membrane potentials. A widely accepted interpretation is that N-methyl-D-aspartate (NMDA) but not α -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are functionally expressed on the subsynaptic membrane. Here we show that, in both CA3 and CA1 hippocampal regions, AMPA-mediated synaptic responses can be detected already at early stages of postnatal development. However, some synapses appear silent because of a very low probability of glutamate release. They can be converted into functional ones by factors that enhance release probability such as paired-pulse stimulation, increasing the temperature or cyclothiazide (CTZ), a drug that blocks AMPA receptor desensitization and increases transmitter release. Conversely, conducting synapses can be switched off by increasing the frequency of stimulation. Although we cannot exclude that "latest AMPA receptors" can become functional after activity-dependent processes, our results clearly indicate that, in the neonatal hippocampus, a proportion of glutamatergic synaptic connections are presynaptically rather than postsynaptically silent.