Goto et al. (2021) Stepwise synaptic plasticity events drive the early phase of
memory consolidation. Science 374(6569), 857-863.
https://www.science.org/doi/10.1126/science.abj9195
“…genetically encoded photosensitizer protein SuperNova (SN), which allows for
chromophore-assisted light inactivation (CALI) of specific molecules in living cells. Upon
illumination at specific wavelengths, SN generates reactive oxygen species that inactivate the
proteins to which it is fused” Authors use “fusion protein of CFL (cofilin) with SN (CFL-SN)” to
inhibit the actin dynamics in dendritic spines associated with LTP.
Mouse hippocampus and anterior cingulate cortex
Authors hypothesized that “…inactivating CFL [cofilin] would lead to destabilization
of the cofilactin structure within the dendritic spine, thereby permitting selective erasure of
sLTP.” They demonstrated this using a fusion protein of CFL with the CALI photosensitizer
protein SuperNova (SN) creating CFL-SN. Photoactivation of CFL-SN up to ~30minutes after
LTP induction reversed structural LTP at the individual spine level. Using this, the authors
demonstrated 3 distinct phases of memory formation that require LTP. Phase #1 (hippocampal
online LTP) is LTP in hippocampus immediately following the shock event. Phase #2
(hippocampal offline LTP) is LPT in the hippocampus during the first day’s sleep period which
the authors argue is required for ensemble stabilization in the hippocampus. Finally, Phase #3
(ACC offline LTP) is LPT in the ACC during the second day’s sleep and is required for system’s
consolidation.
“We found that hippocampal LTP occurs as two distinct temporal processes: online
immediately after learning and offline during periods of sleep. These two processes have
distinct roles: Online LTP establishes the selectivity of neuronal firing to the shock context, as
previously reported (32), and offline LTP is predominantly responsible for the recruitment of
those neurons into repeated bouts of synchronized firing. Synchronized activity was observed
when animals looked into the dark side of the chamber but did not enter, possibly reflecting
recall of the shock context. Our results indicate that this synchronous activity induces
further LTP in neurons, which serves to stabilize the nascent memory engram encoding
the abstract features encompassing an episode. After the two waves of LTP in the
hippocampus, a third wave of extra-hippocampal LTP takes place during sleep the next day in
the ACC; this is required for systems consolidation.”