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Evaluation of Synaptic Multiplicity Using Whole-cell Patch-clamp Electrophysiology
Published on: April 23, 2019
Cholinergic modulation of multivesicular release regulates striatal synaptic potency and integration
Michael J Higley1, Gilberto J Soler-Llavina, Bernardo L Sabatini
1Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA.
Nature Neuroscience
|August 12, 2009
Summary
Neuromodulators like acetylcholine control synaptic strength by reducing glutamate release and concentration. This impacts postsynaptic signaling, influencing how neurons integrate information.
Area of Science:
- Neuroscience
- Synaptic Transmission
- Neuromodulation
Background:
- Neuromodulators have complex effects on synaptic transmission.
- Acetylcholine's role in striatal glutamate release via muscarinic receptors (mAchRs) requires clarification.
- Postsynaptic signaling consequences of acetylcholine modulation are not well understood.
Purpose of the Study:
- To investigate how acetylcholine modulates synaptic transmission in the rat striatum.
- To elucidate the mechanisms by which muscarinic receptor activation affects glutamate release and postsynaptic signaling.
Main Methods:
- Utilized two-photon microscopy for high-resolution imaging of individual synapses.
- Employed glutamate uncaging techniques to precisely control neurotransmitter release.
- Examined synaptic function in the rat striatum.
Main Results:
- Found high multivesicular release (MVR) and low postsynaptic receptor saturation at glutamatergic synapses.
- Demonstrated that muscarinic receptor activation decreases glutamate release probability and synaptic cleft concentration.
- Observed reduced synaptic potential duration and limited temporal summation due to decreased synaptic potency.
Conclusions:
- Presynaptic muscarinic receptor activation controls postsynaptic nonlinearities.
- Basal MVR and low receptor saturation enable neuromodulators to regulate synaptic integration.
- Provides a mechanism for neuromodulatory control of information processing in the striatum.
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