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GABA-activated Single-channel and Tonic Currents in Rat Brain Slices
Published on: July 17, 2011
Bicuculline-resistant paired-pulse inhibition in the rat hippocampal slice
1Department of Pharmacology, University of Glasgow.
Insights
Bicuculline unexpectedly enhanced paired-pulse inhibition in hippocampal slices. This study reveals bicuculline-resistant inhibition involves GABAB receptors and postsynaptic depression, offering new insights into neural circuit regulation.
Area of Science:
- Neuroscience
- Neurophysiology
- Synaptic Plasticity
Background:
- GABAergic inhibition is crucial for regulating neuronal excitability and synaptic plasticity.
- Bicuculline, a GABA-A receptor antagonist, typically reduces inhibition, but an unexpected increase in paired-pulse inhibition was observed.
Purpose of the Study:
- To investigate the mechanisms underlying bicuculline-resistant paired-pulse inhibition in hippocampal slices.
- To elucidate the role of GABAB receptors and postsynaptic mechanisms in this phenomenon.
Main Methods:
- Electrophysiological recordings in rat hippocampal slices.
- Paired-pulse stimulation protocols with varying inter-pulse intervals (i.p.i.).
- Application of bicuculline, 2-hydroxysaclofen, baclofen, and adenosine.
Main Results:
- Bicuculline treatment revealed a medium-latency (300-500 ms i.p.i.) inhibition.
- This inhibition was significantly reduced by 2-hydroxysaclofen and baclofen, indicating GABAB receptor involvement.
- A GABAB-independent postsynaptic depression also contributed to the bicuculline-resistant inhibition.
Conclusions:
- Bicuculline can unmask GABAB-receptor-mediated inhibition and postsynaptic depression in hippocampal circuits.
- GABAB receptors involved in orthodromic inhibition may be presynaptically located on Schaffer collateral terminals.
- These findings provide a deeper understanding of inhibitory mechanisms beyond GABA-A receptor blockade.
Abstract:
1. An initial observation that paired-pulse inhibition in hippocampal slices was increased rather than decreased by bicuculline prompted the present study to explore the mechanism underlying bicuculline-resistant inhibition. 2. In the presence of bicuculline, paired-pulse interactions were dependent on the interpulse interval (i.p.i.) but a medium-latency inhibition was consistently observed at an i.p.i. of 300 to 500 ms. 3. The medium-latency (300 ms) bicuculline-resistant inhibition produced by paired orthodromic stimuli was substantially reduced by 2-hydroxysaclofen and was probably largely mediated by GABAB-receptor activation. Paired-pulse inhibition produced by an orthodromic/antidromic stimulation sequence was not affected by 2-hydroxysaclofen suggesting the possibility that the GABAB-receptors involved in orthodromic inhibition may be located presynaptically on the Schaffer collateral terminals rather than on the postsynaptic surface. The medium latency inhibition was also reduced by baclofen and under some conditions, by adenosine. 4. In addition to the GABAB-component, a hydroxysaclofen-resistant depression of postsynaptic excitability contributed to bicuculline-resistant paired-pulse inhibition at the 300 ms latency.
