Age-related impairment of declarative memory: linking memorization of temporal associations to GluN2B redistribution in dorsal CA1

GluN2B subunits of NMDA receptors have been proposed as a target for treating age‐related memory decline. They are indeed considered as crucial for hippocampal synaptic plasticity and hippocampus‐dependent memory formation, which are both altered in aging. Because a synaptic enrichment in GluN2B is associated with hippocampal LTP in vitro, a similar mechanism is expected to occur during memory formation. We show instead that a reduction of GluN2B synaptic localization induced by a single‐session learning in dorsal CA1 apical dendrites is predictive of efficient memorization of a temporal association. Furthermore, synaptic accumulation of GluN2B, rather than insufficient synaptic localization of these subunits, is causally involved in the age‐related impairment of memory. These challenging data identify extra‐synaptic redistribution of GluN2B‐containing NMDAR induced by learning as a molecular signature of memory formation and indicate that modulating GluN2B synaptic localization might represent a useful therapeutic strategy in cognitive aging

Effect of learning on slow gamma propagation between hippocampus and cortex in the wild-type and AD mice

Abstract Slow gamma oscillations (20–50 Hz) have been suggested to coordinate information transfer between brain structures involved in memory formation. Whereas the involvement of slow gamma in memory processing was studied by means of correlation between the gamma power and the occurrence of a given event (sharp wave ripples (SWRs), cortical transients), our approach consists of the analysis of the transmission of slow gamma itself. We use the method based on Granger causality principle—direct Directed Transfer Function, which allows to determine directed propagation of brain activity, including bidirectional flows. Four cortical sites along with CA1 ipsi- and contralateral were recorded in behaving wild-type and APP/PS1 mice before and after learning session of a spatial memory task. During slow wave sleep propagation of slow gamma was bidirectional, forming multiple loops of interaction which involved both CA1 and some of cortical sites. In episodes coincident with SWRs the number and strength of connectivity pathways increased in both groups compared to episodes without SWRs. The effect of learning was expressed only in APP/PS1 mice and consisted in strengthening of the slow gamma transmission from hippocampus to cortex as well as between both CA1 which may serve more efficient transmission of information from impaired CA1

Extracellular hippocampal acetylcholine level controls amygdala function and promotes adaptive conditioned emotional response

International audienc