Role of P/Q-Ca2+ Channels in Metabotropic Glutamate Receptor 2/3-Dependent Presynaptic Long-Term Depression at Nucleus Accumbens Synapses

The nucleus accumbens (NAc) is an important cerebral area involved in reward and spatial memory (Pennartz et al., 1994), but little is known about synaptic plasticity in this region. Here, electron microscopy revealed that, in the NAc, metabotropic glutamate receptors 2/3 (mGlu2/3) immunostaining wa...

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Bibliographic Details
Published in:The Journal of neuroscience 2002-06, Vol.22 (11), p.4346-4356
Main Authors: Robbe, David, Alonso, Gerard, Chaumont, Severine, Bockaert, Joel, Manzoni, Olivier J
Format: Article
Language:English
Subjects:
Amino Acids - pharmacology
Animals
Bridged Bicyclo Compounds - pharmacology
Calcium - metabolism
Calcium Channel Blockers - pharmacology
Calcium Channels - metabolism
Calcium Channels, P-Type - metabolism
Calcium Channels, Q-Type - metabolism
Cyclic AMP-Dependent Protein Kinases - metabolism
Electric Stimulation
Excitatory Amino Acid Agonists - pharmacology
Excitatory Amino Acid Antagonists - pharmacology
Excitatory Postsynaptic Potentials - drug effects
Excitatory Postsynaptic Potentials - physiology
In Vitro Techniques
Male
Mice
Mice, Inbred C57BL
Neural Inhibition - physiology
Neuronal Plasticity - drug effects
Neuronal Plasticity - physiology
Nucleus Accumbens - cytology
Nucleus Accumbens - metabolism
Patch-Clamp Techniques
Presynaptic Terminals - metabolism
Receptors, Metabotropic Glutamate - agonists
Receptors, Metabotropic Glutamate - antagonists & inhibitors
Receptors, Metabotropic Glutamate - metabolism
Signal Transduction - drug effects
Signal Transduction - physiology
Synapses - metabolism
Synaptic Transmission - drug effects
Synaptic Transmission - physiology
Xanthenes - pharmacology
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Summary:The nucleus accumbens (NAc) is an important cerebral area involved in reward and spatial memory (Pennartz et al., 1994), but little is known about synaptic plasticity in this region. Here, electron microscopy revealed that, in the NAc, metabotropic glutamate receptors 2/3 (mGlu2/3) immunostaining was essentially associated with axonal terminals and glial processes, whereas postsynaptic dendrites and neuronal cell bodies were unstained. Electrophysiological techniques in the NAc slice preparation demonstrated that activation of mGlu2/3 with synaptically released glutamate or specific exogenous agonist, such as LY354740 (200 nm, 10 min), induced long-term depression of excitatory synaptic transmission (mGlu2/3-LTD). Tetanic-LTD and pharmacological mGlu2/3-LTD occluded each other, suggesting common mechanisms. The mGlu2/3-LTD did not require synaptic activity but depended on the cAMP-protein kinase A cascade. Selective inhibition of P/Q-type Ca(2+) channels with omega-agatoxin-IVA occluded the expression of mGlu2/3-LTD, and, conversely, the inhibitory effects of omega-agatoxin-IVA were abolished during mGlu2/3-LTD. Thus, mGlu2/3 play an important role in the control of use-dependent synaptic plasticity at prelimbic cortex-NAc synapses: their activation causes a form of LTD mediated by the long-lasting reduction of P/Q-type Ca(2+)channels contribution to transmitter release.
ISSN:0270-6474
1529-2401
DOI:10.1523/jneurosci.22-11-04346.2002