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Involvement of voltage-sensitive calcium channels in activity-dependent depression of Neuronal signalling in the adult rat hippocampus

Involvement of voltage-sensitive calcium channels in activity-dependent depression of Neuronal signalling in the adult rat hippocampus
Involvement of voltage-sensitive calcium channels in activity-dependent depression of Neuronal signalling in the adult rat hippocampus

Synaptic activity and network excitability in area CA1 of adult rat hippocampal slices were investigated using field potential recordings. Changes in network excitability associated with long-term depression (LTD) were measured using EPSP-to-spike (E-S) curves. Network inhibition was evaluated using a paired-pulse stimulation protocol with a 20 ms inter-pulse interval. The participation of voltage-sensitive calcium channels (VSCCs) in the induction of LTD and in E-S coupling (and dissociation of this E-S relationship) was investigated pharmacologically. A critical assessment was made of published methods of analysing E-S data.

Application of low-frequency stimulation (LFS, 1Hz, 900 pulses) to the Schaffer collateral-commissural fibres of slices at both room temperature and 32°C (at which further work was carried out), induced NMDA receptor-dependent LTD of field EPSP slope (EPSP-S) and population spike amplitude (PS-A), which lasted for at least 30 minutes. Interestingly, after LFS, there was only a small E-S depression but, importantly, paired-pulse inhibition of the PS-A persisted. This novel observation was not due to inability of these slices to express E-S potentiation. Induction of long-term potentiation, as well as application of GABAA antagonists, caused significant E-S potentiation, but with large decreases in inhibition. The full range of changes to the E-S relationship has not been fully described previously, however here; slices were shown to be able to also undergo significant E-S depression when responses to paired-pulse stimuli were compared, i.e. paired-pulse inhibition of the spike lead to E-S depression.

The R/T-type VSCC blocker NiCl2 (50mM) caused highly significant reductions of both EPSP-S and PS-A and a decrease in inhibition. However, paired-pulsed inhibition remained functional (>80%) and only a non-significant E-S depression was observed. NiCl2 significantly reduced the amount of LTD of the PS-A but did not block LTD of the EPSP-S and did not alter the E-S relationship found after LFS under control conditions.

University of Southampton
Marsden, David Peter
3d481273-881f-49e0-aea1-d759823e797c
Marsden, David Peter
3d481273-881f-49e0-aea1-d759823e797c

Marsden, David Peter (2002) Involvement of voltage-sensitive calcium channels in activity-dependent depression of Neuronal signalling in the adult rat hippocampus. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

Synaptic activity and network excitability in area CA1 of adult rat hippocampal slices were investigated using field potential recordings. Changes in network excitability associated with long-term depression (LTD) were measured using EPSP-to-spike (E-S) curves. Network inhibition was evaluated using a paired-pulse stimulation protocol with a 20 ms inter-pulse interval. The participation of voltage-sensitive calcium channels (VSCCs) in the induction of LTD and in E-S coupling (and dissociation of this E-S relationship) was investigated pharmacologically. A critical assessment was made of published methods of analysing E-S data.

Application of low-frequency stimulation (LFS, 1Hz, 900 pulses) to the Schaffer collateral-commissural fibres of slices at both room temperature and 32°C (at which further work was carried out), induced NMDA receptor-dependent LTD of field EPSP slope (EPSP-S) and population spike amplitude (PS-A), which lasted for at least 30 minutes. Interestingly, after LFS, there was only a small E-S depression but, importantly, paired-pulse inhibition of the PS-A persisted. This novel observation was not due to inability of these slices to express E-S potentiation. Induction of long-term potentiation, as well as application of GABAA antagonists, caused significant E-S potentiation, but with large decreases in inhibition. The full range of changes to the E-S relationship has not been fully described previously, however here; slices were shown to be able to also undergo significant E-S depression when responses to paired-pulse stimuli were compared, i.e. paired-pulse inhibition of the spike lead to E-S depression.

The R/T-type VSCC blocker NiCl2 (50mM) caused highly significant reductions of both EPSP-S and PS-A and a decrease in inhibition. However, paired-pulsed inhibition remained functional (>80%) and only a non-significant E-S depression was observed. NiCl2 significantly reduced the amount of LTD of the PS-A but did not block LTD of the EPSP-S and did not alter the E-S relationship found after LFS under control conditions.

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Published date: 2002

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Local EPrints ID: 464810
URI: http://eprints.soton.ac.uk/id/eprint/464810
PURE UUID: 5295bb50-aaf1-459d-a8aa-ab57dc213f81

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Date deposited: 05 Jul 2022 00:02
Last modified: 16 Mar 2024 19:45

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Author: David Peter Marsden

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