A retrograde mechanism coordinates memory allocation across brain regions

Abstract

Memories engage ensembles of neurons across different brain regions within a memory system. However, it is unclear whether the allocation of a memory to these ensembles is coordinated across brain regions. To address this question, we used CREB expression to bias memory allocation in one brain region, and rabies retrograde tracing to test memory allocation in connected presynaptic neurons in the other brain regions. We find that biasing allocation of CTA memory in the basolateral amygdala (BLA) also biases memory allocation in presynaptic neurons of the insular cortex (IC). By manipulating the allocation of CTA memory to specific neurons in both BLA and IC, we found that we increased their connectivity and enhanced CTA memory performance. These results – which are corroborated by mathematical simulations, and by studies with auditory fear conditioning – demonstrate that a retrograde mechanism coordinates the allocation of memories across different brain regions.

Engram Stability and Maturation During Systems Consolidation Underlies Remote Memory

“…The hippocampus receives and integrates input from multiple brain structures. To investigate the input sources of the CA1 ensemble cells, i.e., which cells impinge upon them during the different stages of memory acquisition and recall, we used the pseudorabies approach ( 30 ) that was used for a different purpose in the CA1 ( 50 ) and was recently used to study recent memory in the amygdala ( 51 ): we first expressed the mutated avian tumor virus (TVA) receptor (TC66T) and glycoprotein (oPBG) in ensemble cells by injecting AAV2-CAG-flex-TC66T-mCherry and AAV2-CAG-flex-oPBG into the dCA1 of TRAP2 mice (Fos tm2.1(icre/ERT2)Luo ) expressing CreER protein under the cFos promoter. Three weeks later, mice underwent a fear conditioning task, and 4-OHT was introduced during either acquisition, recent, or remote recall, allowing the Cre to enter the nucleus in the active ensemble cells and induce the expression of TVA and the glycoprotein (Figure 3A).…”