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NMDA-Independent LTP by adenosine A2 receptor-mediated postsynaptic AMPA potentiation in hippocampus.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Kessey, Kofi Mogul, David J. |
| Copyright Year | 1997 |
| Abstract | The role of adenosine A2 receptors in normal synaptic transmission and tetanus-induced long-term potentiation (LTP) was tested by stimulation of the Schaffer collateral pathway and recording of the field excitatory postsynaptic potential (EPSP) in the CA1 region of rat transverse hippocampal slices. Activation of adenosine A2 receptors with the A2 agonist N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine (DPMA; 20 nM) enhanced synaptic transmission during low-frequency test pulses (0. 033 Hz). Paired stimulation before and during DPMA exposure indicated no paired-pulse facilitation as a result of A2 activation, suggesting that enhancement was not a result of presynaptic modulation. DPMA enhanced the early phase alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) component of the EPSP. In contrast, DPMA had no effect on the N-methyl--aspartate (NMDA) component isolated using low extracellular Mg2+ and the AMPA receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione (20 microM), indicating that the effects of A2 activation on synaptic transmission were mediated by a postsynaptic enhancement of the AMPA response. Activation of adenosine A2 receptors during a brief tetanus (100 Hz, 1 s) increased the level of LTP by 36% over that seen in response to a tetanus under control conditions. DPMA exposure after prior induction of LTP showed no additional potentiation, indicating that the mechanisms that contribute to both types of increases in synaptic transmission share a common mechanism. A slow onset NMDA-independent LTP could be induced by application of a tetanus during perfusion of DPMA with the NMDA blocker AP5 (50 microM). Blockade of L-type Ca channels with nifedipine (10 microM) had no effect on normal synaptic transmission but reduced NMDA-independent LTP by 32%. Very little NMDA-independent LTP could be induced after prior saturation of NMDA-dependent LTP via multiple tetani spaced 10 min apart, indicating that both forms of LTP are eventually convergent on a common mechanism, presumably the postsynaptic AMPA receptor response. Because extracellular adenosine levels are modulated by cellular activity throughout the brain and because adenosine receptor activation can markedly alter levels of synaptic transmission independent of NMDA receptors, adenosine may play an important and complex role as a modulator of synaptic transmission in the brain. |
| Starting Page | 387 |
| Ending Page | 406 |
| Page Count | 20 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://jn.physiology.org/content/jn/78/4/1965.full.pdf |
| PubMed reference number | 9325364v1 |
| Volume Number | 78 |
| Issue Number | 4 |
| Journal | Journal of neurophysiology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | AMPA Receptors Adenosine A2 Receptors Aspartic Acid CA1 field Calcium Excitatory Postsynaptic Potentials Hertz (Hz) Long-Term Potentiation Long-Term Synaptic Depression Modulator Device Component N-Methyl-D-Aspartate Receptors N-Methylaspartate Nifedipine Receptor Activation Process Receptors, Purinergic P1 Synaptic Transmission Tetany Thioctic Acid chemosensitization/potentiation facilitation |
| Content Type | Text |
| Resource Type | Article |
