Hippocampal Memory Traces Are Differentially Modulated by Experience, Time, and Adult Neurogenesis

Abstract

SUMMARY Memory traces are believed to be ensembles of cells used to store memories. To visualize memory traces, we created a transgenic line that allows for the comparison between cells activated during encoding and expression of a memory. Mice re-exposed to a fear-inducing context froze more and had a greater percentage of reactivated cells in the dentate gyrus (DG) and CA3 than mice exposed to a novel context. Over time, these differences disappeared, in keeping with the observation that memories become generalized. Optogenetically silencing DG or CA3 cells that were recruited during encoding of a fear-inducing context prevented expression of the corresponding memory. Mice with reduced neurogenesis displayed less contextual memory and less reactivation in CA3 but, surprisingly, normal reactivation in the DG. These studies suggest that distinct memory traces are located in the DG and in CA3 but that the strength of the memory is related to reactivation in CA3.

Memory retrieval by activating engram cells in mouse models of early Alzheimer’s disease

“…Using this technology, several groups have demonstrated that DG neurons activated during CFC learning are both sufficient 11 -14 and necessary 15 for subsequent memory retrieval. In addition, our recent study found that engram cells under protein synthesis inhibitor-induced amnesia were capable of driving acute memory recall if they are directly activated optogenetically 14 .…”

Memory Retrieval in Mice and Men

“…Given the highly parallel nature of neural connectivity and processing, it is possible that although these ensembles may be sufficient for retrieval, they are not necessary as other pathways could compensate. The question of necessity was addressed in two recent studies using a light-gated proton pump from archaebacteria (ArchT) to hyperpolarize and silence cfos tagged neural ensembles in experiments analogous to those described above with ChR2 (Denny et al 2014;Tanaka et al 2014). Both teams of investigators also used context fear conditioning and examined the requirement for ensembles in three different hippocampal regions, the DG, CA3, and CA1.…”

Dendritic Spikes Provide a Mechanism for Hippocampal Replay and Sharp-Wave/Ripple Generation

“…These events display temporal dynamics, which suggest they may be important for synaptic modification in cortical targets whose activity increases after SPW/Rs as would be predicted by the "two-step" hypothesis (Markram et al, 1997). Consistent with this hypothesis, enhancing or suppressing SPW/Rs enhances and impairs memory consolidation, respectively (Girardeau et al, 2009;Barnes and Wilson, 2014).…”

“…In awake behaving animals, cholinergic modulation suppresses the activity of recurrent hippocampal connections and gives priority to the incoming sensory stream from the entorhinal cortex, which then is encoded into the short-term store of the hippocampus (for review, see Gupta and Hasselmo, 2014). Recall can occur at a later time, by reactivation of the same neurons active during encoding by use of a retrieval cue (Garner et al, 2012;Liu et al, 2012).…”