Biology subjects

Nicole, O.

Publications and source records attributed to Nicole, O..

2 recordsLinked to original sources

bioRxiv2026

Anterior cingulate cortex engram drives post traumatic stress disorder-like memory impairments in a rodent model of traumatic fear

Fear memories in post-traumatic stress disorder are marked by persistent cue-driven recollection and impaired contextual recall, yet the engram organization underlying this maladaptive state remains unclear. Here we used a rodent model combining contextual fear conditioning with systemic corticosterone to mimic trauma-associated glucocorticoid exposure. This paradigm generated a PTSD-like phenotype characterized by hypermnesia for a trauma-related but irrelevant (non-predictive of the threat) cue and contextual amnesia. Activity-dependent tagging and reactivation mapping revealed that traumatic memory is supported by a regionally dysregulated engram pattern, with enhanced recruitment of the anterior cingulate cortex (ACC) and basolateral amygdala (BLA), and reduced engagement of the dentate gyrus (DG). These changes persisted over time and correlated with the severity of the behavioral phenotype. Chemogenetic inhibition of ACC engram cells abolished traumatic memory expression, restored contextual recall, and normalized engram reactivation across DG and BLA. In contrast, inhibition of randomly tagged ACC or hippocampal populations had no such effect, indicating that the ACC engram is specifically required for traumatic memory expression. Together, these findings show that PTSD-like memory is not simply an amplified fear trace, but a distinct maladaptive engram state distributed across cortical-hippocampal- amygdalar circuits.

neuroscience↗

bioRxiv2024

Early intrinsic plasticity of ACC engram neurons defines memory formation and precision

Neocortical memory engrams are thought to stabilize and mature via enhanced interconnectivity during the so-called systems-consolidation process 1,2. While synaptic plasticity of these engram connections is considered an important mechanism for storing memories 3,4, it cannot fully account for the dynamic vividness of remote, cortically-based memories. Indeed, cell-intrinsic plasticity has been touted as the crucial early priming mechanism that renders nascent engram neurons susceptible to ongoing plastic processes while providing flexibility for later encoding events 5-7. Here, we reveal that learning-related neuron-wide intrinsic excitability (IE) plasticity of nascent cortical engram neurons is a permissive mechanism for the formation and specificity of remote associative memories. Using a c-fos-dependent genetic and viral system for the targeted labeling of engram neurons in the anterior cingulate cortex (ACC) combined with ex vivo electrophysiology, we found that contextual fear learning triggered a time-dependent increase in their IE signature expressed over days during the early, but not late, phase of memory formation. Remarkably, chemogenetically hyperpolarizing engram neurons during this early plastic phase enhanced their maturation, increasing the strength and context-precision of consolidated memories and preventing memory disturbance caused by an interference event. Altogether, our findings identify cell-intrinsic plasticity within nascent ACC engram neurons as an essential tagging mechanism whose features determine the fate and dynamic content of remote memories.

neuroscience↗