Cardozo, L. M. | bioRxiv Science

bioRxiv2022

Localized Synaptic Potentiation is Necessary and Sufficient for Context Fear Memory

The nature and distribution of the synaptic changes that underlie memory are not well understood. We examined the synaptic plasticity behind context fear conditioning and found that learning produced synaptic potentiation specifically onto engram neurons in the basolateral amygdala. This potentiation lasted at least 7 days, was reversed by extinction, and its disruption impaired memory recall. High frequency optogenetic stimulation of the CS and US-activated ensembles, or biochemical induction of synaptic potentiation in US-responsive neurons alone, was sufficient to produce a context fear association without prior associative training. These results suggest that plasticity of CS inputs onto US-responsive amygdala neurons underlies memory formation and is necessary and sufficient to establish context fear associations.

neuroscience↗

bioRxiv2019

Fear Learning Induces Long-Lasting Changes in Gene Expression and Pathway Specific Presynaptic Growth

The stabilization or consolidation of long-term memories lasting more than a few hours requires new gene expression. While neural activity has been shown to induce expression of a variety of genes within several hours of learning, whether this leads to persistent changes in gene expression that lasts for days or weeks remains unclear. We developed a novel mouse line which expresses Cre recombinase in an inducible manner and used it to examine gene expression in learning-activated neurons of the medial prefrontal cortex (mPFC) one month following contextual fear conditioning. The mPFC is not required for the initial retrieval of contextual memory but becomes necessary after one month, suggesting a slowly developing plasticity. We found a variety of changes in gene expression in learning-activated neural ensembles that were specific to the mPFC. One group of transcriptional changes observed was the coordinated upregulation of presynaptic proteins suggesting a potential learning-induced elaboration of presynaptic terminals. We tested this idea by labeling the projections of mPFC neurons active during initial learning and found an increase in the number of terminals in neurons projecting to the basolateral amygdala at 1 month following training. These results suggest a presynaptic growth mechanism that could account for the enhanced role of the mPFC in fear memory retrieval at long time points after learning.

neuroscience↗