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Cortical Serotonin Type 2A Receptor Activation Shields Episodic-like Memories from Retroactive Interference in
Juan Facundo Morici1, Mariana Imperatori1, Pablo Koss1,2
1Instituto de Neurociencia Cognitiva y Traslacional (INCYT), CONICET, Fundación INECO, Universidad Favaloro, C1060 Buenos Aires, Argentina.
ACS Chemical Neuroscience
|May 16, 2026
Summary
Retroactive interference (RI) impairs memory consolidation. Activating serotonin 2A receptors (5-HT2AR) in the medial prefrontal cortex (mPFC) prevents RI, suggesting memories are hindered, not erased.
Area of Science:
- Neuroscience
- Cognitive Science
- Behavioral Neuroscience
Background:
- Temporally close information acquisition can impair memory consolidation, leading to retroactive interference (RI).
- The medial prefrontal cortex (mPFC) and the serotonergic system are implicated in regulating memory interference.
- Serotonin 2A receptors (5-HT2AR) in the mPFC influence memory retrieval, but their role in RI modulation is unclear.
Purpose of the Study:
- To investigate the role of serotonin 2A receptors (5-HT2AR) in modulating retroactive interference (RI).
- To determine if 5-HT2AR signaling is necessary for preventing RI and to explore its effects on memory expression.
Main Methods:
- Utilized a modified object recognition task in rodents to induce RI.
- Administered pharmacological agents to manipulate 5-HT2AR activity.
- Assessed the impact of RI and 5-HT2AR manipulation on memory recall.
Main Results:
- Retroactive interference (RI) was found to specifically impair the object-related component of memory.
- Serotonin signaling through 5-HT2AR was demonstrated to be necessary for preventing RI.
- Activation of 5-HT2AR before memory retrieval rescued memories affected by RI.
Conclusions:
- Retroactive interference (RI) may not erase memory traces but rather impedes their access.
- Serotonin 2A receptor (5-HT2AR) signaling in the medial prefrontal cortex (mPFC) plays a crucial role in mitigating RI.
- Targeting 5-HT2AR may offer therapeutic potential for memory disorders characterized by interference.
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