Nucleus reuniens of the thalamus controls fear memory reconsolidation

Diverse therapeutic developments for post-traumatic stress disorder (PTSD) indicate common mechanisms of memory modulation

“…Intra-BLA administration of NMDA N2A antagonist NVP-AAM077 before reactivation of memory reduced the freezing on test day while it did not affect the amnesia caused by anisomycin suggesting it did not have an effect on memory destabilization but disrupted the restabilization of reconsolidating memory (Milton, et al, 2013). Furthermore, administration of NMDA N2A antagonist TCN-201 in nucleus reuniens of thalamus after memory reactivation disrupted the reconsolidation of fear memory (Troyner & Bertoglio, 2021). This suggests that nonselective NMDA receptor antagonists disrupt fear memory reconsolidation mainly through their action on NMDA N2A receptors.…”

Synaptic plasticity regulated by phosphorylation of PSD-95 Serine 73 in dorsal CA1 is required for contextual fear extinction

“…Human studies also showed that EC-CA1 projections are activated by cognitive prediction error (that may drive memory extinction), while CA3-CA1 projections are activated by memory recall without prediction errors (Bein et al, 2020). The role of the Re in fear memory encoding, retrieval, extinction and generalisation has been demonstrated (Ramanathan et al, 2018;Troyner and Bertoglio, 2021;Xu and Sudhof, 2013). Still, it has to be established whether the plasticity of dCA1 synapses is specific to Re and/or EC projections.…”

Pathways for Memory, Cognition and Emotional Context: Hippocampal, Subgenual Area 25, and Amygdalar Axons Show Unique Interactions in the Primate Thalamic Reuniens Nucleus

“…In the absence of a direct pathway from mPFC to hippocampus, prefrontal signals must be conveyed to hippocampus through a third area, such as the entorhinal cortex or RE, both of which have bidirectional connections with the hippocampus and mPFC (Barbas, 2000a;Varela et al, 2014). This tripartite system involving RE has been associated with memory, ranging from acquisition to extinction (Troyner and Bertoglio, 2021), and for sequential events (Jayachandran et al, 2019). In addition, RE mediates hippocampus-mPFC synchronization during slow-wave sleep, promoting information transfer and memory consolidation (Roy et al, 2017;Hauer et al, 2019).…”

“…Connections from hippocampus likely transmit contextual information to RE needed to flexibly gauge behavioral responses in a changing environment, such as learning to avoid stimuli that signal danger and extinguish fear responses when the stimuli no longer signify danger (Ramanathan et al, 2018a). The centrality of RE for contextual significance of memories is exemplified by the consequences after its destruction, leading to degraded mnemonic specificity and overgeneralization (Xu and Sudhof, 2013;Ramanathan et al, 2018b;Ramanathan and Maren, 2019;Linley et al, 2021;Silva et al, 2021;Troyner and Bertoglio, 2021).…”

“…Situated directly above the third ventricle, the reuniens nucleus (RE) is the most ventral of the midline thalamic nuclei in rats, mice, and primates. Through strong bidirectional connections with the hippocampus and mPFC, studies in rats have revealed a pivotal role of RE in cognitive functions including spatial working memory, memory consolidation, and strategy shifting (Cholvin et al, 2013;Prasad et al, 2013;Saalmann, 2014;Ramanathan et al, 2018a;Hauer et al, 2019;Troyner and Bertoglio, 2021). Because the medial prefrontal cortex (mPFC) does not project directly to hippocampus, connections through RE provide a conduit for mPFC signals to enter the hippocampus (Cassel et al, 2013), a communication that is necessary for cognitive processes.…”