Transcriptional regulation of ventral hippocampus-nucleus accumbens circuit excitability drives cocaine seeking - PubMed
6 hours ago
- #transcriptional regulation
- #neuroscience
- #cocaine addiction
- The study investigates how transcriptional regulation in the ventral hippocampus (vHPC)-nucleus accumbens (NAc) circuit affects cocaine seeking behavior.
- FosB/ΔFosB transcription factor, induced by cocaine, plays a critical role in cocaine seeking and reward, particularly in vHPC-NAc neurons.
- Circuit-specific knockout of FosB/ΔFosB in vHPC-NAc neurons impaired cocaine reward expression and abstinence-induced seeking.
- Cocaine exposure decreases vHPC-NAc excitability, mediated by ΔFosB expression.
- Cocaine induces a FosB/ΔFosB-dependent increase in calreticulin expression, an endoplasmic reticulum calcium-buffering protein, which mediates vHPC-NAc excitability and is necessary for cocaine reward.
- The findings reveal a noncanonical mechanism where cocaine increases calreticulin in vHPC, leading to decreased excitability and driving cocaine seeking and reward.