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GluN2B-mediated regulation of silent synapses for receptor specification and addiction memory

Summary

Researchers studied how a specific brain protein called GluN2B affects addiction memories from cocaine use. They found that removing this protein reduced the formation of ‘silent synapses’ – immature brain connections created by cocaine – and weakened drug-related memories. However, this also unexpectedly made mice more active, suggesting that GluN2B normally helps control both addiction memory and activity levels. The findings provide new insights into how addiction memories form and suggest potential ways to treat addiction.

Background

Cocaine addiction involves reemergence of silent synapses containing only NMDA-type glutamate receptors in the nucleus accumbens. GluN2B-containing NMDA receptors are abundant in these silent synapses, but their operational mechanisms in addiction memory are not fully understood.

Objective

To examine the synaptic and behavioral roles of GluN2B-containing NMDA receptors in silent synapses following repeated cocaine exposure, using conditional depletion of GluN2B in D1-expressing accumbal medium spiny neurons.

Results

GluN2B ablation reduced silent synapse proportion but some persisted through GluN2C substitution, driving aberrant incorporation of calcium-impermeable AMPARs. This precocious synapse maturation impaired addiction memory but increased locomotor activity, effects normalized by blocking calcium-impermeable AMPAR trafficking.

Conclusion

GluN2B supports the competence of cocaine-induced silent synapses to specify AMPAR subunit composition and thereby regulate addiction memory expression and related behaviors, revealing new insights into addiction mechanisms and potential therapeutic targets.
  • Published in:Experimental & Molecular Medicine,
  • Study Type:Experimental Research,
  • Source: 39930130
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