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Differences in chloride gradients allow for three distinct types of synaptic modulation by endocannabinoids
Yanqing Wang1, Brian D Burrell2
1Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, South Dakota; and Center for Brain and Behavior Research, Sanford School of Medicine, University of South Dakota, Vermillion, South Dakota.
Journal of Neurophysiology
|May 27, 2016
Summary
Differences in chloride ion (Cl-) gradients determine whether endocannabinoids depress or enhance synaptic activity. This study in leeches reveals how Cl- gradients dictate synaptic plasticity, impacting neural circuit output.
Area of Science:
- Neuroscience
- Synaptic Plasticity
- Ion Gradients
Background:
- Endocannabinoids modulate synaptic transmission, causing depression or disinhibition of neural circuits.
- The role of chloride ion (Cl-) gradients in directing these endocannabinoid effects remains unclear.
- The medicinal leech (Hirudo verbana) offers a well-characterized model for studying central nervous system (CNS) synaptic plasticity.
Purpose of the Study:
- To investigate how differences in Cl- gradients regulate endocannabinoid-mediated synaptic depression versus disinhibition.
- To determine the involvement of transient potential receptor vanilloid (TRPV) channels in these processes.
- To explore how distinct patterns of afferent stimulation influence endocannabinoid effects.
Main Methods:
- Exogenous application of endocannabinoids and capsaicin to leech CNS.
- Pharmacological manipulation of Cl- export and import.
- Electrophysiological recording of synaptic responses in identified neurons (P, Nmech, Npoly cells).
- Stimulation protocols including low-frequency stimulation (LFS) and high-frequency stimulus (HFS).
Main Results:
- Endocannabinoid-mediated potentiation of P synapses was blocked by inhibiting Cl- export.
- Endocannabinoid-mediated depression of Nmech synapses was prevented by blocking Cl- import, indicating disinhibition of excitatory GABAergic input.
- Npoly synapses showed direct depression, with elevated Cl- equilibrium potentials (ECl) potentially protecting against disinhibition.
- All observed plasticity required transient potential receptor vanilloid (TRPV) channel activation.
- LFS induced endocannabinoid-mediated depression in Npoly synapses; HFS induced potentiation in P synapses and depression in Nmech synapses.
Conclusions:
- Differences in neuronal Cl- gradients are critical in determining the direction (potentiation or depression) of endocannabinoid-mediated synaptic modulation.
- Elevated ECl in GABA-depolarized neurons plays a role in synaptic plasticity, potentially protecting against disinhibition.
- Endocannabinoid signaling and synaptic plasticity are tightly regulated by ion gradients and neuronal stimulation patterns, mediated via TRPV channels.
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