Induction of activity synchronization among primed hippocampal neurons out of random dynamics is key for trace memory formation and retrieval

Abstract

Memory is thought to be encoded by sparsely distributed neuronal ensembles in memory‐related regions. However, it is unclear how memory‐eligible neurons react during learning to encode trace fear memory and how they retrieve a memory. We implemented a fiber‐optic confocal fluorescence endomicroscope to directly visualize calcium dynamics of hippocampal CA1 neurons in freely behaving mice subjected to trace fear conditioning. Here we report that the overall activity levels of CA1 neurons showed a right‐skewed lognormal distribution, with a small portion of highly active neurons (termed Primed Neurons) filling the long‐tail. Repetitive training induced Primed Neurons to shift from random activity to well‐tuned synchronization. The emergence of activity synchronization coincided with the appearance of mouse freezing behaviors. In recall, a partial synchronization among the same subset of Primed Neurons was induced from random dynamics, which also coincided with mouse freezing behaviors. Additionally, training‐induced synchronization facilitated robust calcium entry into Primed Neurons. In contrast, most CA1 neurons did not respond to tone and foot shock throughout the training and recall cycles. In conclusion, Primed Neurons are preferably recruited to encode trace fear memory and induction of activity synchronization among Primed Neurons out of random dynamics is critical for trace memory formation and retrieval.

Bidirectional regulation of distinct memory domains by α5-subunit-containing GABAAreceptors in CA1 pyramidal neurons

“…According to a recent study, there is a small pool (∼10%) of CA1 pyramidal neurons that are inherently active under resting/ free exploration conditions (named "primed neurons" by the authors), while 70% of pyramidal neurons remain silent regardless of behavioral state, with the rest falling into an intermediate zone between the two extremes (Zhou et al 2020). Trace fear-conditioning did not alter the overall activity architecture of CA1 pyramidal neurons, however, increased coherence and signal-to-noise ratio (SNR) among the primed neurons, without increasing activity of the silent neurons.…”

Entorhinal cortical Island cells regulate temporal association learning with long trace period

“…5 B,C). Our experiment disinhibited the processed input from MECIII ( Kitamura et al 2014 ), leaving the rest of the HPC processing apparatus largely intact for fine-tuned processing of an artificially boosted temporal signal ( McEchron et al 2003 ; Pastalkova et al 2008 ; MacDonald et al 2011 ; Pelkey et al 2017 ; Marks et al 2019 ; Zhang et al 2019 ; Zhou et al 2020 ). Therefore, this experiment suggests that the Island cells in the MEC exert control over the allowed length of time between events that can become associated across time.…”

The Quest for the Hippocampal Memory Engram: From Theories to Experimental Evidence

“…Further, by silencing CA1 engram neurons during memory retrieval, Tanaka and colleagues found compromised reactivation of cortical ensembles (Masamizu et al, 2014 ), confirming a direct link between the CA1 engram and cortical representations. Once an engram has formed, in vivo calcium imaging studies have revealed greater synchrony and higher repetitive activity in engram cells compared to non-engram cells, even in the absence of cue presentation (Ghandour et al, 2019 ; Zhou et al, 2020 ). Together, these data strongly support an indexing function for the hippocampal engram.…”