Differential Contributions of Glutamatergic Hippocampal→Retrosplenial Cortical Projections to the Formation and Persistence of Context Memories

Abstract

Learning to associate stressful events with specific environmental contexts depends on excitatory transmission in the hippocampus, but how this information is transmitted to the neocortex for lasting memory storage is unclear. We identified dorsal hippocampal (DH) projections to the retrosplenial cortex (RSC), which arise mainly from the subiculum and contain either the vesicular glutamate transporter 1 (vGlut1) or vGlut2. Both vGlut1+ and vGlut2+ axons strongly excite and disynaptically inhibit RSC pyramidal neurons in superficial layers, but vGlut2+ axons trigger greater inhibition that spreads to deep layers, indicating that these pathways engage RSC circuits via partially redundant, partially differentiated cellular mechanisms. Using contextual fear conditioning in mice to model contextual associative memories, together with chemogenetic axonal silencing, we found that vGlut1+ projections are principally involved in processing recent context memories whereas vGlut2+ projections contribute to their long-lasting storage. Thus, within the DH→RSC pathway, engagement of vGlut1+ and vGlut2+ circuits differentially contribute to the formation and persistence of fear-inducing context memories.

Secondary Motor Cortex Transforms Spatial Information into Planned Action During Navigation

“…In this respect, it follows that M2 tuning to spatial context 22 may be a remnant of an integration process in which spatial information is transformed into an 23 appropriate motor plan. 24 We conclude that M2 ensemble activity discriminates, in a manner largely independent of 25 spatial context, the specific motor acts associated with navigation constrained to paths. We 26 also conclude that such activity can contribute to both the planning and execution of action.…”

“…Specific features 3 of cortico-hippocampal connectivity point to retrosplenial and posterior parietal cortex as 4 intermediaries in this encoding process. Retrosplenial (RSP) and posterior parietal (PPC) 5 cortices are interconnected with hippocampus, subiculum, and perirhinal, postrhinal, and 6 entorhinal cortices [16][17][18][19][20][21][22][23][24] . These two regions contain neurons representing information in multiple 7 egocentric and allocentric reference frames 9,[25][26][27][28][29][30][31][32][33] and boast dense projections to secondary 8 motor cortex (M2) [34][35][36] .…”

Uniquely excitable neurons enable precise and persistent information transmission through the retrosplenial cortex

“…Of even more direct relevance is the persistent nature of the navigational information being received and processed by the superficial RSC. The subiculum represents one of these key functional inputs to RSC L2/3 cells (Wyss and van Groen, 1992;Yamawaki et al, 2019bYamawaki et al, , 2019a. Subicular neurons, particularly those in the postsubiculum, display a strong preference for particular orientations and are thus called head direction (HD) cells (Taube et al, 1990).…”

“…We next used these biophysically-realistic models to understand the information processing capabilities of LR versus RS neurons. The subicular complex provides one of the most prominent sources of input to the superficial layers of the RSC (Yamawaki et al, 2019a). Most cells in the subicular complex fire selectively when an animal is facing a particular direction and are hence called head-direction (HD) cells (Taube et al, 1990).…”

“…The RSC receives prominent spatial and memory-related inputs from the hippocampus, subicular complex, anterior thalamus, secondary motor cortex, and visual cortex, as well as the contralateral RSC Wyss, 1990, 2003;Wyss and van Groen, 1992;Miyashita and Rockland, 2007). Recent studies have started to document the functional nature of these inputs to the RSC (Yamawaki et al, 2016, 2019a, 2019bSempere-Ferràndez et al, 2018;Sempere-ferràndez et al, 2019). However, the precise properties of the RSC neuronal subtypes involved Sugar et al, 2011;Kurotani et al, 2013) is rarely studied and the local connectivity between RSC subtypes completely unknown.…”