Memory recall and modifications by activating neurons with elevated CREB

Abstract

Memory is supported by a specific ensemble of neurons distributed in the brain that form a unique memory trace. We previously showed that neurons in the lateral amygdala expressing elevated levels of cAMP response-element binding protein are preferentially recruited into fear memory traces and are necessary for the expression of those memories. However, it is unknown whether artificially activating just these selected neurons in the absence of behavioral cues is sufficient to recall that fear memory. Using an ectopic rat vanilloid receptor TRPV1 and capsaicin system, we found that activating this specific ensemble of neurons was sufficient to recall established fear memory. Furthermore, this neuronal activation induced a reconsolidation-like reorganization process, or strengthening of the fear memory. Thus, our findings establish a direct link between the activation of specific ensemble of neurons in the lateral amygdala and the recall of fear memory and its subsequent modifications.

Inhibition of Lactate Transport Erases Drug Memory and Prevents Drug Relapse

“…The blockade of lactate transport to neurons by DAB or MCT1/MCT2-ODN administration prevented the phosphorylation of CREB and ERK 1-2 h after memory retrieval. Additionally, previous studies showed that pCREB, pcofilin, and pERK are critical for memory reconsolidation (73)(74)(75). Thus, lactate transport may be a critical functional link between astrocytic glycogenolysis and the regulation of neuronal gene expression in memory reconsolidation.…”

Memory retrieval of inhibitory avoidance requires histamine H 1 receptor activation in the hippocampus

“…Indeed, retrieval is not simply a static readout of stored information; rather, it represents a dynamic process that can be studied separately from either acquisition or consolidation, with which it shares similar mechanisms (1,7,8). Furthermore, retrieval can elicit specific processes that modify the recalled memory (9). In this regard, protein synthesis, a necessary step in the transfer of a labile short-term memory into a stable long-term memory (LTM) (2), is required to enable retrieval, because infusion of protein synthesis inhibitors in the amygdala 10 min before retrieval impaired fear memory expression (10).…”

Pharmacogenetic reactivation of the original engram evokes an extinguished fear memory

“…For example, optogenetic reactivation of neuronal ensembles in the hippocampal DG or retrosplenial cortex that were activated during contextual fear conditioning has been shown to be sufficient to elicit freezing in a novel unconditioned context (Liu et al, 2012;Cowansage et al, 2014). Similarly in the lateral amygdala, reactivating the specific neuronal ensemble in which fear memory was allocated with elevated levels of cAMP response-element binding protein (CREB) was able to induce freezing (Kim et al, 2014). These studies suggest that conditioned fear memory engram resides in distributed brain regions including the hippocampal DG, neocortex, and lateral M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 13 amygdala.…”