Hippocampal efferents to retrosplenial cortex and lateral septum are required for memory acquisition

Abstract

Learning and memory involves a large neural network of many brain regions, including the notable hippocampus along with the retrosplenial cortex (RSC) and lateral septum (LS). Previous studies have established that the dorsal hippocampus (dHPC) plays a critical role during the acquisition and expression of episodic memories. However, the role of downstream circuitry from the dHPC, including the dHPC-to-RSC and dHPC-to-LS pathways, has come under scrutiny only recently. Here, we employed an optogenetic approach with contextual fear conditioning in mice to determine whether the above two pathways are involved in acquisition and expression of contextual fear memory. We found that a selective inhibition of the dHPC neuronal terminals in either the RSC or LS during acquisition impaired subsequent memory performance, suggesting that both the dHPC-to-RSC and dHPC-to-LS pathways play a critical role in memory acquisition. We also selectively inhibited the two dHPC efferent pathways during memory expression and found a differential effect on memory performance. These results indicate the intricacies of memory processing and that hippocampal efferents to cortical and subcortical regions may be differentially involved in aspects of physiological and cognitive memory processes.

Putting Together Pieces of the Lateral Septum: Multifaceted Functions and Its Neural Pathways

“…First, transection of the CA1/Sub projection to the LS to anatomically disrupt this pathway abolishes fear responses upon exposure to a fearful context or cue (Hunsaker et al, 2009). Second, optogenetic inhibition of the dCA1/Subdm-LS pathway decreases freezing responses upon exposure to a fearful context (Opalka and Wang, 2020). These results provide initial evidence of the role of the dCA1/Subdm-LS pathway in promoting fear, though more evidence is needed to confirm this notion.…”

“…Growing evidence supports the role of the LS in fear memory processes. First, the LS is critical for fear memory acquisition, as disruption of LS activity during fear conditioning training impairs subsequent memory performance, evidenced by reduced freezing responses upon re-exposure to footshock chambers (Calandreau et al, 2010;Calandreau et al, 2007;Desmedt et al, 1999;Hunsaker et al, 2009;Opalka and Wang, 2020). Notably, this role of the LS in acquisition appears to be dependent on its input from the hippocampus (Hunsaker et al, 2009;Opalka and Wang, 2020).…”

“…First, the LS is critical for fear memory acquisition, as disruption of LS activity during fear conditioning training impairs subsequent memory performance, evidenced by reduced freezing responses upon re-exposure to footshock chambers (Calandreau et al, 2010;Calandreau et al, 2007;Desmedt et al, 1999;Hunsaker et al, 2009;Opalka and Wang, 2020). Notably, this role of the LS in acquisition appears to be dependent on its input from the hippocampus (Hunsaker et al, 2009;Opalka and Wang, 2020). Second, the LS is critical for fear memory consolidation, as a post-training manipulation of the LS (intra-LS administration of CRF) immediately after an inhibitory avoidance task enhances relevant fear memory (Lee, 1995); however, more studies are needed to confirm this notion.…”

Retrosplenial and hippocampal synchrony during retrieval of old memories in macaques

“…Both the hippocampus and retrosplenial cortex are important structures for forming long-lasting memories of spatiotemporally distinct events (1-2). The neural mechanisms within these structures that give rise to retrieval over large time spans is unclear, though the retrosplenial cortex may assume a greater, more independent role over time (3)(4)(5)(6)(7)(8)(9). Tests of this role have been limited by i. species-adapted tasks in rodents that use shorter delays and restricted memorandum, ii.…”

“…In rats and mice, the neural ensembles in RSC coordinate their activity with hippocampal ensembles (5,9,11,12), and these interactions may be essential for the laying down of longlasting mnemonic representations. To assess interactions between these two structures, we calculated their debiased weighted phase lag index (wPLI) during sigma bouts obtained from search, inter-trial-intervals, and rest epochs.…”