Abstract
We remember our lives as sequences of events, but it is unclear how these memories are controlled during retrieval. In rats, the prelimbic cortex (PL) is positioned to influence sequence memory through extensive top-down inputs to regions heavily interconnected with the hippocampus, notably the nucleus reuniens of the thalamus (RE) and perirhinal cortex (PER). Here we used an hM4Di synaptic-silencing approach to test our hypothesis that specific PL→RE and PL→PER projections regulate sequence memory retrieval. First, we found that suppressing PL activity impaired sequence memory. Second, we found that inhibiting PL→RE and PL→PER pathways effectively abolished sequence memory. Finally, we performed a sequential lag analysis showing that the PL→RE pathway contributes to a working memory retrieval strategy, whereas the PL→PER pathway contributes to a temporal context memory retrieval strategy. These findings demonstrate that the PL→RE and PL→PER pathways serve as top-down mechanisms that control sequence memory retrieval strategies.
Highlights
We remember our lives as sequences of events, which is at the core of episodic memory
Incubation Time of AAV-hM4Di (Adeno-Associated Virus) in medial prefrontal cortex (mPFC) Neurons We targeted mPFC, which has been implicated in the temporal organization of memory (Uylings et al, 2003; Devito and Eichenbaum, 2011; Tiganj et al, 2017, 2018), using an axon-preferring hM4Di variant (AAV9.CAG.mCherry-2a-hM4Dinrxn.WPRE.SV40), referred to as hM4Dinrxn
The gestation time for these experiments was determined by injecting hM4Di in a separate group of rats (n = 4, 1 per time point) that were perfused at 1, 2, 4, or 8 weeks after surgery
Summary
We remember our lives as sequences of events, which is at the core of episodic memory. Memory for sequences of events relies on the hippocampus (HC) (Fortin et al, 2002; Kesner et al, 2002; Allen et al, 2016) and medial prefrontal cortex (mPFC). MPFC may bias different sequence retrieval strategies through its top-down projection pathways. MPFC is ideally situated to influence memory retrieval through its projections to the thalamus and cortex (Sesack et al, 1989; Chiba et al, 2001; Vertes, 2002; Hoover and Vertes, 2007). If this is the case, selective inhibition of distinct mPFC projection pathways should impair sequence memory with different effects
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
