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Aminoglycoside antibiotics affect hippocampal LTP: a comparative study with the N-type calcium antagonist
C Frank1, Y C Zeng, S Sagratella
1Department of Pharmacology, Istituto Superiore di Sanità, Roma, Italy.
Abstract:
The in vitro activity of N-type calcium antagonists such as omega-conotoxin-GVIA and the aminoglycoside antibiotics neomycin and streptomycin was studied in rat hippocampal slices. The effects of the drugs were tested on basal CA1 synaptic transmission and on the hippocampal long-term potentiation (LTP) induced by tetanic electrical stimulation and by increasing (4mM) the calcium concentration. Omega-conotoxin-GVIA, neomycin and streptomycin were able to significantly reduce the amplitude of the CA1 population spike at 1 microM, 0.5 mM and 1 mM, respectively. In addition, the drugs affected the induction and maintenance of the CA1 tetanic and calcium-induced LTP at concentrations which did not modify the magnitude of the control CA1 population spike. Omega-conotoxin-GVIA (0.5 microM), neomycin (0.3 mM) and streptomycin (0.7 mM) perfused for 60 min, before inducing LTP, prevented the subsequent increase of the CA1 population spike in all the experiments. The same concentrations of these drugs perfused for 60-min after a previously established LTP significantly reduced the amplitude of the CA1 population spike. The results promote a role for the N-type calcium channels and for the release of neurotransmitters in both the induction and the maintenance of hippocampal LTP.
Insights
N-type calcium channel blockers, omega-conotoxin-GVIA, neomycin, and streptomycin, inhibit hippocampal long-term potentiation (LTP) in rats. These drugs impact both the induction and maintenance phases of synaptic plasticity.
Area of Science:
- Neuroscience
- Pharmacology
- Cellular Biology
Background:
- Hippocampal long-term potentiation (LTP) is a key cellular mechanism for learning and memory.
- N-type calcium channels and neurotransmitter release are implicated in synaptic plasticity.
Purpose of the Study:
- To investigate the effects of N-type calcium antagonists (omega-conotoxin-GVIA) and aminoglycoside antibiotics (neomycin, streptomycin) on hippocampal CA1 synaptic transmission and LTP.
- To determine the role of N-type calcium channels in LTP induction and maintenance.
Main Methods:
- In vitro electrophysiology in rat hippocampal slices.
- Assessment of basal CA1 synaptic transmission.
- Induction of LTP via tetanic stimulation and increased calcium concentration.
- Application of omega-conotoxin-GVIA, neomycin, and streptomycin at varying concentrations.
Main Results:
- Omega-conotoxin-GVIA, neomycin, and streptomycin significantly reduced CA1 population spike amplitude.
- These drugs inhibited both the induction and maintenance of LTP without affecting basal synaptic transmission.
- Pre- and post-LTP application of drugs prevented or reversed LTP, respectively.
Conclusions:
- N-type calcium channels play a crucial role in both the induction and maintenance of hippocampal LTP.
- Neurotransmitter release, modulated by these channels, is essential for synaptic plasticity.
- Omega-conotoxin-GVIA, neomycin, and streptomycin serve as valuable tools for studying LTP mechanisms.