Antisense oligonucleotides to the GluR2 AMPA receptor subunit modify excitatory synaptic transmission in vivo
| Autor: | Alejandro Caicedo, Nicole Renard, Rémy Pujol, Jean-Luc Puel, Jérôme Ruel, Christine D'Aldin |
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| Rok vydání: | 1998 |
| Předmět: |
Receptor complex
Protein subunit Guinea Pigs Action Potentials Nerve Tissue Proteins Perilymph AMPA receptor Neurotransmission Biology Synaptic Transmission Diffusion Cellular and Molecular Neuroscience Drug Delivery Systems medicine Animals Receptors AMPA Cloning Molecular Receptor Molecular Biology Cochlear Nerve Cochlea Hair Cells Auditory Inner Glutamate receptor Oligonucleotides Antisense Cell biology medicine.anatomical_structure nervous system Acoustic Stimulation Audiometry Pure-Tone Neuron Neuroscience |
| Zdroj: | Brain research. Molecular brain research. 55(1) |
| ISSN: | 0169-328X |
| Popis: | In the brain, fast excitatory synaptic transmission is mostly mediated by the α -amino-3-hydroxy-5-methyl-isoxazole-propionic acid (AMPA) subtype of the glutamate receptors. Molecular cloning has revealed that four subunits, GluR1, GluR2, GluR3, and GluR4 form heteromeric receptors with high affinity for AMPA. Because antagonists and agonists do not discriminate between individual AMPA receptor subunits, we decided to use antisense oligonucleotides to block the expression of the GluR2 subunit within the receptor complex in adult animals. In the present study, we exploited several advantages afforded by the guinea pig cochlea to determine whether an antisense oligonucleotide directed to the mRNA of the GluR2 subunit could modify primary auditory neurotransmission. While a random probe with the same base composition had no effect, a GluR2 antisense oligonucleotide, continuously delivered into the cochlea, transiently reduced the compound action potential and diminished spontaneous activity of single auditory nerve fibers. Although antisense oligonucleotides penetrated a variety of cells, their effect could be physiologically localized to a single site of GluR2 antisense probe action, the primary auditory neuron. Subunit specificity of this effect was confirmed by a significant reduction in GluR2/3, but not GluR4 immunoreactivity in primary auditory neurons. Besides being the first demonstration that transient knockout of GluR2 subunit in adult animal modifies excitatory synaptic transmission in vivo, these results support the use of the antisense strategy as a powerful tool for blocking expression of any gene in the cochlea. |
| Databáze: | OpenAIRE |
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