Time-dependent inhibition of Rac1 in the VTA enhances long-term aversive memory: implications in active forgetting mechanisms

Abstract The fate of memories depends mainly on two opposing forces: the mechanisms required for the storage and maintenance of memory and the mechanisms underlying forgetting, being the latter much less understood. Here, we show the effect of inhibiting the small Rho GTPase Rac1 on the fate of inhi...

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Main Authors: Juliana F. Dalto, Jorge H. Medina
Format: Article
Language:English
Published: Nature Portfolio 2023-08-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-40434-9
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author Juliana F. Dalto
Jorge H. Medina
author_facet Juliana F. Dalto
Jorge H. Medina
author_sort Juliana F. Dalto
collection DOAJ
description Abstract The fate of memories depends mainly on two opposing forces: the mechanisms required for the storage and maintenance of memory and the mechanisms underlying forgetting, being the latter much less understood. Here, we show the effect of inhibiting the small Rho GTPase Rac1 on the fate of inhibitory avoidance memory in male rats. The immediate post-training micro-infusion of the specific Rac1 inhibitor NSC23766 (150 ng/0.5 µl/ side) into the ventral tegmental area (VTA) enhanced long-term memory at 1, 7, and 14 days after a single training. Additionally, an opposed effect occurred when the inhibitor was infused at 12 h after training while no effect was observed immediately after testing animals at 1 day. Control experiments ruled out the possibility that post-training memory enhancement was due to facilitation of memory formation since no effect was found when animals were tested at 1 h after acquisition and no memory enhancement was observed after the formation of a weak memory. Immediate post-training micro-infusion of Rac1 inhibitor into the dorsal hippocampus, or the amygdala did not affect memory. Our findings support the idea of a Rac1-dependent time-specific active forgetting mechanism in the VTA controlling the strength of a long-term aversive memory.
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spelling doaj.art-ce24593ac2554e7685cd3d0c8bc7ca912023-11-20T09:14:04ZengNature PortfolioScientific Reports2045-23222023-08-0113111010.1038/s41598-023-40434-9Time-dependent inhibition of Rac1 in the VTA enhances long-term aversive memory: implications in active forgetting mechanismsJuliana F. Dalto0Jorge H. Medina1Instituto de Biología Celular y Neurociencias “Prof. Eduardo de Robertis”, Facultad de Medicina, Universidad de Buenos Aires-CONICETInstituto de Biología Celular y Neurociencias “Prof. Eduardo de Robertis”, Facultad de Medicina, Universidad de Buenos Aires-CONICETAbstract The fate of memories depends mainly on two opposing forces: the mechanisms required for the storage and maintenance of memory and the mechanisms underlying forgetting, being the latter much less understood. Here, we show the effect of inhibiting the small Rho GTPase Rac1 on the fate of inhibitory avoidance memory in male rats. The immediate post-training micro-infusion of the specific Rac1 inhibitor NSC23766 (150 ng/0.5 µl/ side) into the ventral tegmental area (VTA) enhanced long-term memory at 1, 7, and 14 days after a single training. Additionally, an opposed effect occurred when the inhibitor was infused at 12 h after training while no effect was observed immediately after testing animals at 1 day. Control experiments ruled out the possibility that post-training memory enhancement was due to facilitation of memory formation since no effect was found when animals were tested at 1 h after acquisition and no memory enhancement was observed after the formation of a weak memory. Immediate post-training micro-infusion of Rac1 inhibitor into the dorsal hippocampus, or the amygdala did not affect memory. Our findings support the idea of a Rac1-dependent time-specific active forgetting mechanism in the VTA controlling the strength of a long-term aversive memory.https://doi.org/10.1038/s41598-023-40434-9
spellingShingle Juliana F. Dalto
Jorge H. Medina
Time-dependent inhibition of Rac1 in the VTA enhances long-term aversive memory: implications in active forgetting mechanisms
Scientific Reports
title Time-dependent inhibition of Rac1 in the VTA enhances long-term aversive memory: implications in active forgetting mechanisms
title_full Time-dependent inhibition of Rac1 in the VTA enhances long-term aversive memory: implications in active forgetting mechanisms
title_fullStr Time-dependent inhibition of Rac1 in the VTA enhances long-term aversive memory: implications in active forgetting mechanisms
title_full_unstemmed Time-dependent inhibition of Rac1 in the VTA enhances long-term aversive memory: implications in active forgetting mechanisms
title_short Time-dependent inhibition of Rac1 in the VTA enhances long-term aversive memory: implications in active forgetting mechanisms
title_sort time dependent inhibition of rac1 in the vta enhances long term aversive memory implications in active forgetting mechanisms
url https://doi.org/10.1038/s41598-023-40434-9
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