Cocaine inverts rules for synaptic plasticity of glutamate transmission in the ventral tegmental area

Mameli, Manuel; Bellone, Camilla; Brown, Matthew T.; Lüscher, Christian

doi:10.1038/nn.2763

Cited by 153 publications

(159 citation statements)

References 15 publications

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“…2C). In the VTA, a single injection of cocaine leads to a change in AMPAR subunit composition from GluA2-containing to GluA2-lacking (Bellone and Lüscher, 2006;Mameli et al, 2011). We found that the RIs in LHb 3 RMTg neurons from the saline and cocaine groups were not significantly different (Fig.…”

Section: Cocaine Postsynaptically Potentiates Ampar-mediated Transmismentioning

confidence: 71%

“…Photolysis was optimized by adjusting the laser beam position and power (3-10 mW) such that laser-evoked EPSCs [(L)-EPSCs] yielded amplitudes and kinetics similar to mEPSCs. AMPA/NMDA ratios of (L)-EPSCs were obtained by dividing the peak of AMPA-EPSC at Ϫ60 mV and the NMDA-EPSCs at ϩ40 mV at 30 ms after onset as previously described (Mameli et al, 2011).…”

Section: Methodsmentioning

confidence: 99%

“…Hippocampal interneurons and DA neurons in the VTA undergo long-term synaptic changes through GluA2-lacking AMPAR- mediated calcium influx (Lamsa et al, 2007;Mameli et al, 2011). Given that cocaine increases the levels of AMPARs in LHb 3 RMTg neurons, we asked whether cocaine experience altered long-term synaptic plasticity rules.…”

Section: Cocaine Drives Metaplasticity In the Lhbmentioning

confidence: 99%

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Cocaine Evokes Projection-Specific Synaptic Plasticity of Lateral Habenula Neurons

Maroteaux

Mameli

2012

J. Neurosci.

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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.

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Section: Cocaine Postsynaptically Potentiates Ampar-mediated Transmismentioning

confidence: 71%

Section: Methodsmentioning

confidence: 99%

Section: Cocaine Drives Metaplasticity In the Lhbmentioning

confidence: 99%

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Cocaine Evokes Projection-Specific Synaptic Plasticity of Lateral Habenula Neurons

Maroteaux

Mameli

2012

J. Neurosci.

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“…CP-AMPARs also accumulate in the mouse NAc after a similar regimen in association with enhanced cocaine craving (Mameli et al, 2009). From the standpoint of synaptic transmission, the presence of CPAMPARs is expected to have important consequences, such as providing a route for Ca 2 þ entry other than NMDARs and thus altering the 'rules' for induction of synaptic plasticity (eg, Mameli et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Different Adaptations in AMPA Receptor Transmission in the Nucleus Accumbens after Short vs Long Access Cocaine Self-Administration Regimens

Purgianto

Scheyer

Loweth

et al. 2013

Neuropsychopharmacol

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Ca 2 þ -permeable AMPA receptors (CP-AMPARs) accumulate in the nucleus accumbens (NAc) after B1 month of withdrawal from a long-access cocaine self-administration regimen (6 h/d, 10d). This is functionally significant because CP-AMPARs mediate the 'incubated' cue-induced cocaine craving produced by this regimen. Our present goal was to determine if other commonly employed cocaine selfadministration regimens also elicit CP-AMPAR accumulation. We compared four regimens, named according to whether sessions were short-access (ShA, 2 h) or long-access (LgA, 6 h) and the total number of sessions: LgA/10d (already shown to elicit CP-AMPAR accumulation), ShA/11d, ShA/20-24d, and LgA/20-24d. In the latter regimens, rats began with 10 days of ShA and then entered a differential phase (10-14 days) in which ShA sessions either continued or switched to LgA. Controls self-administered saline. After 440 days of withdrawal, whole-cell patch-clamp recordings were performed in NAc core medium spiny neurons to assess the contribution of CP-AMPAR transmission, based on the magnitude of synaptic suppression elicited by bath application of the selective CP-AMPAR antagonist naspm (100 mM). Naspm produced a non-significant (B10%) attenuation of electrically evoked local excitatory postsynaptic current in the saline and ShA groups. By contrast, a significant naspm-induced synaptic attenuation (25-30%) was observed in both the LgA groups. Further analyses indicate that this emergence of CP-AMPAR transmission in the LgA groups is associated with increased baseline responsiveness of MSN to excitatory drive. Together with data on cocaine infusions in each group, our results show that CP-AMPAR accumulation and enhanced glutamate transmission is associated with longer sessions (6 h), rather than the number of sessions or cocaine infusions.

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“…Whole-cell patch-clamp recordings confirmed that these light pulses applied close to spines on secondary dendrites of CA1 pyramidal neurons reproducibly evoked synaptic responses (see Fig. 5A; n ϭ 5; Mameli et al, 2011). The amount of photo-released glutamate was adjusted by changing the number of pulses.…”

Section: Methodsmentioning

confidence: 61%

Alteration of Synaptic Network Dynamics by the Intellectual Disability Protein PAK3

Dubos¹,

Combeau²,

Bernardinelli³

et al. 2012

J. Neurosci.

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Several gene mutations linked to intellectual disability in humans code for synaptic molecules implicated in small GTPase signaling. This is the case of the Rac/Cdc42 effector p21-activated kinase 3 (PAK3). The mechanisms responsible for the intellectual defects and the consequences of the mutation on the development and wiring of brain networks remain unknown. Here we show that expression of PAK3 mutants, suppression of PAK3, or inhibition of PAK3 function in rat hippocampal slice cultures interfere with activity-mediated spine dynamics. Inhibition of PAK3 resulted in two main alterations: (1) an increased growth of new, unstable spines, occurring in clusters, and mediated by activity; and (2) an impairment of plasticity-mediated spine stabilization interfering with the formation of persistent spines. Additionally, we find that PAK3 is specifically recruited by activity from dendrites into spines, providing a new mechanism through which PAK3 could participate in the control of both spine stabilization and local spine growth. Together, these data identify a novel function of PAK3 in regulating activity-mediated rearrangement of synaptic connectivity associated with learning and suggest that defects in spine formation and refinement during development could account for intellectual disability.

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Cocaine inverts rules for synaptic plasticity of glutamate transmission in the ventral tegmental area

Cited by 153 publications

References 15 publications

Cocaine Evokes Projection-Specific Synaptic Plasticity of Lateral Habenula Neurons

Cocaine Evokes Projection-Specific Synaptic Plasticity of Lateral Habenula Neurons

Different Adaptations in AMPA Receptor Transmission in the Nucleus Accumbens after Short vs Long Access Cocaine Self-Administration Regimens

Alteration of Synaptic Network Dynamics by the Intellectual Disability Protein PAK3

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