Frequency-dependent depression of excitatory synaptic transmission is independent of activation of MCPG-sensitive presynaptic metabotropic glutamate receptors in cultured hippocampal neurons
| Autor: | Robert G. Maki, Marc A. Dichter, D. D. Cummings |
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| Rok vydání: | 1995 |
| Předmět: |
Agonist
medicine.medical_specialty Physiology medicine.drug_class Glycine Presynaptic Terminals Hippocampal formation Neurotransmission Receptors Metabotropic Glutamate Benzoates Hippocampus Synaptic Transmission chemistry.chemical_compound Internal medicine medicine Extracellular Animals Cells Cultured Neurons Chemistry musculoskeletal neural and ocular physiology General Neuroscience Antagonist Electric Stimulation Rats Endocrinology nervous system Metabotropic glutamate receptor Excitatory postsynaptic potential ACPD Neuroscience Excitatory Amino Acid Antagonists |
| Zdroj: | Journal of neurophysiology. 74(4) |
| ISSN: | 0022-3077 |
| Popis: | 1. A paired-pulse paradigm, and a high-frequency train followed by a test pulse, were used to investigate the possible role of presynaptic metabotropic glutamate receptors (mGluRs) in frequency-dependent modulation of the amplitude of excitatory post-synaptic currents (EPSCs). Paired whole cell patch-clamp recordings from monosynaptically connected hippocampal neurons maintained in very low-density cultures were performed, using the mGluR antagonist (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG, 500 microM) and the mGluR agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD, 100 microM]. 2. Paired-pulse depression (PPD) was observed in all the excitatory pairs recorded. The average PPD ratio (amplitude of the 2nd EPSC divided by the amplitude of the 1st EPSC) was 0.80 +/- 0.1 (SD) (n = 8). Application of the mGluR antagonist MCPG had no effect on the amplitude of the EPSCs and did not affect the ratio of the two EPSCs (PPD ratio 0.79 +/- 0.2). 3. The amplitudes of 10 successive EPSCs stimulated at a high frequency (20 Hz) decremented on average in both 4 mM extracellular Ca2+ (n = 5) and in 1 mM extracellular Ca2+ (n = 6). In all pairs tested, posttetanic depression (PTD) was observed (PTD ratio 0.7 +/- 0.2). Bath application of MCPG (500 microM) did not affect the amplitudes of the EPSCs during the train; MCPG also did not affect PTD. 4. The mGluR agonist (1S,3R)-ACPD depressed the amplitudes of the EPSCs in both the paired-pulse (1st EPSC, 35 +/- 9%; 2nd EPSC, 36 +/- 10%) and posttetanic pulse (1 and 4 mM extracellular Ca2+) paradigms. The amount of depression observed, both PPD and PTD, remained unaffected by application of (1S,3R)-ACPD. Coapplication of the antagonist MCPG (500 microM) blocked the effects of (1S,3R)-ACPD (100 microM). 5. We conclude that frequency-dependent depression of EPSC amplitudes occurs independent of endogenous activation of MCPG-sensitive mGluRs in cultured hippocampal neurons. Moreover, we demonstrate that exogenous activation of mGluRs by the agonist (1S,3R)-ACPD can produce additional EPSC depression above that already present due to frequency-dependent mechanisms. |
| Databáze: | OpenAIRE |
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