Journal
JOURNAL OF NEUROSCIENCE
Volume 32, Issue 36, Pages 12641-12646Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2405-12.2012
Keywords
-
Categories
Funding
- Paris Neuroscience School (ENP)
- INSERM ATIP-AVENIR
- City of Paris
Ask authors/readers for more resources
Addictive drugs share the ability to increase dopamine (DA) levels and trigger synaptic adaptations in the mesocorticolimbic system, two cellular processes engaged in the early stages of drug seeking. Neurons located in the lateral habenula (LHb) modulate the activity of DA neurons and DA release, and adaptively tune goal-directed behaviors. Whether synaptic modifications in LHb neurons occur upon drug exposure remains, however, unknown. Here, we assessed the influence of cocaine experience on excitatory transmission onto subsets of LHb neurons using a combination of retrograde tracing and ex vivo patch-clamp recordings in mice. Recent evidence demonstrates that AMPA receptors lacking the GluA2 subunit mediate glutamatergic transmission in LHb neurons. We find that cocaine selectively potentiates AMPA receptor-mediated EPSCs in LHb neurons that send axons to the rostromedial tegmental nucleus, a GABAergic structure that modulates the activity of midbrain DA neurons. Cocaine induces a postsynaptic accumulation of AMPA receptors without modifying their subunit composition or single-channel conductance. As a consequence, a protocol pairing presynaptic glutamate release with somatic hyperpolarization, to increase the efficiency of GluA2-lacking AMPA receptors, elicited a long-term potentiation in neurons only from cocaine-treated mice. This suggests that cocaine resets the rules for the induction of synaptic long-term plasticity in the LHb. Our study unravels an early, projection-specific, cocaine-evoked synaptic potentiation in the LHb that may represent a permissive step for the functional reorganization of the mesolimbic system after drug exposure.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available