Compartmentalized dendritic plasticity in the retrosplenial cortex integrates memories across time

Abstract

Events occurring close in time are often linked in memory, providing an episodic timeline and a framework for those memories. Recent studies suggest that memories acquired close in time are encoded by overlapping neuronal ensembles, and that this overlap is necessary for memory linking. Transient increases in neuronal excitability drive this ensemble overlap, but whether dendritic plasticity plays a role in linking memories is unknown. Here, we show that contextual memory linking is not only dependent on ensemble overlap in the retrosplenial cortex (RSC), but also on RSC branch-specific dendritic allocation mechanisms. Using longitudinal two-photon calcium imaging of RSC dendrites, we show that the same dendritic segments are preferentially activated by two linked (but not independent) contextual memories, and that spine clusters added after each of two linked (but not independent) contextual memories are allocated to the same dendritic segments. Importantly, with a novel optogenetic tool, selectively targeted to activated dendritic segments following learning, we show that reactivation of dendrites tagged during the first context exploration is sufficient to link two contextual memories. These results demonstrate a causal role for dendritic mechanisms in memory linking and reveal a novel set of rules that govern how linked, and independent memories are allocated to dendritic compartments.

Miniscope-LFOV: A large field of view, single cell resolution, miniature microscope for wired and wire-free imaging of neural dynamics in freely behaving animals

“…Here, we demonstrate the MiniLFOV enables single cell resolution across the entire FOV ( Fig. 5a ) by imaging GCaMP6f-expressing dorsal cortex 44,45 through a 4 mm × 4 mm cranial window in head-fixed mice running on a 29-mm circular treadmill ( Fig. 5a, s12a ).…”

Intrinsic neural excitability induces time-dependent overlap of memory engrams

“…Here, we built a model that is able to reproduce the overlap among memory engrams of events that are temporally linked. These overlaps have been observed in the amygdala (Rashid et al ., 2016), the hippocampus (Cai et al ., 2016) and the retrosplenial cortex (Sehgal et al ., 2021) while it has been reported that these three regions are involved in a memory consolidation process known as systems consolidation (Tonegawa et al ., 2018; Kitamura et al ., 2017). However, it remains unclear what information is transferred from one region to another and investigating a potential transfer of overlap between brain regions would help understand how temporal memory linking evolves over the course of systems consolidation.…”

“…This transient increase is likely due to the learning-induced expression of the transcription factor CREB (Rashid et al ., 2016; Silva et al ., 2009; Han et al ., 2007), which is known to play a role in regulating neural excitability (Dong et al ., 2006). As a result, time-varying excitability may account for overlapping neural ensembles encoding memories of events that are temporally linked (Sehgal et al ., 2018), namely events spaced by a short temporal delay, as observed in the lateral amygdala (Rashid et al ., 2016), the hippocampal dorsal CA1 (Cai et al ., 2016; Shen et al ., 2022), and the retrosplenial cortex (Sehgal et al ., 2021). Previous theoretical works have described how the dynamics of plasticity-related proteins and excitability can lead to co-allocation of memories at the dendritic level (Kastellakis et al ., 2016; Sehgal et al ., 2021; Chowdhury et al ., 2021).…”

“…As a result, time-varying excitability may account for overlapping neural ensembles encoding memories of events that are temporally linked (Sehgal et al ., 2018), namely events spaced by a short temporal delay, as observed in the lateral amygdala (Rashid et al ., 2016), the hippocampal dorsal CA1 (Cai et al ., 2016; Shen et al ., 2022), and the retrosplenial cortex (Sehgal et al ., 2021). Previous theoretical works have described how the dynamics of plasticity-related proteins and excitability can lead to co-allocation of memories at the dendritic level (Kastellakis et al ., 2016; Sehgal et al ., 2021; Chowdhury et al ., 2021). Attractor networks (Amit, 1989) have been previously used to describe the recurrent network properties of overlapping memory engrams (Gastaldi et al ., 2021) but without taking excitability into account.…”

“…Previous theoretical works have described how the dynamics of plasticity-related proteins and excitability can lead to co-allocation of memories at the dendritic level (Kastellakis et al, 2016;Sehgal et al, 2021;Chowdhury et al, 2021). Attractor networks (Amit, 1989) have been previously used to describe the recurrent network properties of overlapping memory engrams (Gastaldi et al, 2021) but without taking excitability into account.…”