Hippocampus and amygdala fear memory engrams re-emerge after contextual fear relapse.

The formation and extinction of fear memories represent two forms of learning that each engage the hippocampus and amygdala. How cell populations in these areas contribute to fear relapse, however, remains unclear. Here, we demonstrate that, in male mice, cells active during fear conditioning in the dentate gyrus of hippocampus exhibit decreased activity during extinction and are re-engaged after contextual fear relapse. In vivo calcium imaging reveals that relapse drives population dynamics in the basolateral amygdala to revert to a network state similar to the state present during fear conditioning. Finally, we find that optogenetic inactivation of neuronal ensembles active during fear conditioning in either the hippocampus or amygdala is sufficient to disrupt fear expression after relapse, while optogenetic stimulation of these same ensembles after extinction is insufficient to artificially mimic fear relapse. These results suggest that fear relapse triggers a partial re-emergence of the original fear memory representation, providing new insight into the neural substrates of fear relapse.

Social behavior in mice following chronic optogenetic stimulation of hippocampal engrams.

The hippocampus processes both spatial-temporal information and emotionally salient experiences. To test the functional properties of discrete sets of cells in the dorsal dentate gyrus (dDG), we examined whether chronic optogenetic reactivation of these ensembles was sufficient to modulate social behaviors in mice. We found that chronic reactivation of discrete dDG cell populations in male mice largely did not affect social behaviors in an experience-dependent manner. However, we found that social behavior in a female exposure task was increased following chronic optogenetic stimulation when compared to pre-stimulation levels, suggesting that the protocol led to increased social behavior, although alternative explanations are discussed. Furthermore, multi-region analysis of neural activity did not yield detectable differences in immediate-early gene expression or neurogenesis following chronic optogenetic stimulation. Together, these results suggest that the effects of chronic optogenetic stimulation in the dDG on social behaviors are independent of the contextual experience processed by each cellular ensemble.

Aged rats with intact memory show distinctive recruitment in cortical regions relative to young adults in a cue mismatch task.

Similar to elderly humans, aged Long-Evans rats exhibit individual differences in performance on tasks that critically depend on the medial temporal lobe memory system. Although reduced memory performance is common, close to half of aged rats in this outbred rodent population perform within the range of young subjects, exhibiting a stable behavioral phenotype that may signal a resilience to memory decline. Increasing evidence from research on aging in the Long-Evans study population supports the existence of adaptive neural change rather than avoidance of detrimental effects of aging on the brain, indicating a malleability of brain function over the life span that may preserve optimal function. Augmenting prior work that centered on hippocampal function, the current study extends investigation to cortical regions functionally interconnected with the hippocampal formation, including medial temporal lobe cortices and posterior components of the default mode network. In response to an environmental manipulation that creates a mismatch in the expected cue orientation, aged rats with preserved memory show greater activation across an extended network of cortical regions as measured by immediate early gene expression. In contrast, young subjects, behaviorally similar to the aged rats in this study, show a more limited cortical response. This distinctive cortical recruitment in aged unimpaired rats, set against a background of comparable activation across hippocampal subregions, may represent adaptive cortical recruitment consistent with evidence in human studies of neurocognitive aging. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Aged rats with preserved memory dynamically recruit hippocampal inhibition in a local/global cue mismatch environment.

Similar to elderly humans, aged outbred Long-Evans rats exhibit individual differences in memory abilities, including a subset of aged rats that maintain memory function on par with young adults. Such individuals provide a basis for investigating mechanisms of resilience to age-related decline. The present study examined hippocampal gene expression in young adults and aged rats with preserved memory function under behavioral task conditions well established for assessing information processing central to the formation of episodic memory. Although behavioral measures and hippocampal gene induction associated with neural activity and synaptic plasticity were similar across age groups, a marker for inhibitory interneuron function in the hippocampal formation was distinctively increased only in aged rats but not in young adults. Because heightened hippocampal neural activity is associated with age-related memory impairment across species, including rats, monkeys, and humans, this finding may represent an adaptive homeostatic adjustment necessary to maintain neural plasticity and memory function in aging.