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Vibrodissociation of Neurons from Rodent Brain Slices to Study Synaptic Transmission and Image Presynaptic Terminals
Published on: May 25, 2011
Depolarizing GABAergic synaptic input triggers endocannabinoid-mediated retrograde synaptic signaling.
Michael J Urbanski1, Flora E Kovacs, Bela Szabo
1Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Albert-Ludwigs-Universität, Freiburg i Br, Germany.
Synapse (New York, N.Y.)
|April 7, 2009
Summary
Depolarizing GABAergic input triggers endocannabinoid production in postsynaptic neurons, which then inhibits GABA release. This newly identified pathway involves calcium channel activation and CB(1) receptors.
Area of Science:
- Neuroscience
- Cellular Neuroscience
- Synaptic Plasticity
Background:
- Endocannabinoids (eCBs) are retrograde messengers synthesized in postsynaptic neurons.
- eCBs inhibit neurotransmitter release from presynaptic terminals, modulating synaptic transmission.
- Increased postsynaptic calcium concentration is a known stimulus for eCB production.
Purpose of the Study:
- To investigate if depolarizing GABAergic synaptic input can trigger eCB production.
- To elucidate the mechanisms and physiological significance of eCB production induced by GABAergic input.
Main Methods:
- Patch-clamp electrophysiology and calcium imaging in mouse cerebellar slices.
- Recording of spontaneous inhibitory postsynaptic currents (sIPSCs) under different conditions.
- Pharmacological manipulation using CB(1) receptor antagonist (rimonabant) and diacylglycerol lipase inhibitor (orlistat).
Main Results:
- Depolarizing GABAergic sIPSCs induced calcium spikes in postsynaptic Purkinje cells.
- A short-term suppression of sIPSCs followed calcium spikes, indicating retrograde signaling.
- This suppression was dependent on CB(1) receptors and 2-arachidonoylglycerol, but not anandamide degradation.
- In young mice, depolarizing GABAergic input occurred at a low rate and did not show signs of endocannabinoid tone.
Conclusions:
- Depolarizing GABAergic synaptic input represents a novel trigger for endocannabinoid production.
- This process involves postsynaptic calcium channel activation and subsequent CB(1) receptor-mediated suppression of GABA release.
- The findings reveal a new regulatory mechanism for GABAergic neurotransmission.
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