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Fear memory formation and recall are highly regulated processes, with the central amygdala (CeA) contributing to fear memory-related behaviors. We recently reported that a remote fear memory engram is resident in the anterior basolateral amygdala (aBLA). However, the extent to which downstream neurons in the CeA participate in this engram is unknown. We tested the hypothesis that CeA neurons activated during fear memory formation are reactivated during remote memory retrieval such that a CeA engram participates in remote fear memory recall and its associated behavior. Using contextual fear conditioning in TRAP2;Ai14 mice, we identified, by persistent Cre-dependent tdTomato expression (i.e., "TRAPing"), CeA neurons that were c-fos -activated during memory formation. Twenty-one days later, we quantified neurons activated during remote memory recall using Fos immunohistochemistry. Dual labeling was used to identify the subpopulation of CeA neurons that was both activated during memory formation and reactivated during recall. Compared with their context-conditioned (no shock) controls, fear-conditioned (electric shock) mice ( n = 5/group) exhibited more robust fear memory-related behavior (freezing) as well as larger populations of activated (tdTomato + ) and reactivated (dual-labeled) CeA neurons. Most neurons in both groups were mainly located in the capsular CeA subdivision (CeAC). Notably, however, only the size of the TRAPed population distributed throughout the CeA was significantly correlated with time spent freezing during remote fear memory recall. Our findings indicate that fear memory formation robustly activates CeA neurons and that a subset located mainly in the CeAC may contribute to both remote fear memory storage/retrieval and the resulting fear-like behavior., (© 2023 Hammack et al.; Published by Cold Spring Harbor Laboratory Press.)

Introduction: Threatening environmental cues often generate enduring fear memories, but how these are formed and stored remains actively investigated. Recall of a recent fear memory is thought to reflect reactivation of neurons, in multiple brain regions, activated during memory formation, indicating that anatomically distributed and interconnected neuronal ensembles comprise fear memory engrams. The extent to which anatomically specific activation-reactivation engrams persist during long-term fear memory recall, however, remains largely unexplored. We hypothesized that principal neurons in the anterior basolateral amygdala (aBLA), which encode negative valence, acutely reactivate during remote fear memory recall to drive fear behavior., Methods: Using adult offspring of TRAP2 and Ai14 mice, persistent tdTomato expression was used to "TRAP" aBLA neurons that underwent Fos-activation during contextual fear conditioning (electric shocks) or context only conditioning (no shocks) ( n = 5/group). Three weeks later, mice were re-exposed to the same context cues for remote memory recall, then sacrificed for Fos immunohistochemistry., Results: TRAPed (tdTomato +), Fos +, and reactivated (double-labeled) neuronal ensembles were larger in fear- than context-conditioned mice, with the middle sub-region and middle/caudal dorsomedial quadrants of aBLA displaying the greatest densities of all three ensemble populations. Whereas tdTomato + ensembles were dominantly glutamatergic in context and fear groups, freezing behavior during remote memory recall was not correlated with ensemble sizes in either group., Discussion: We conclude that although an aBLA-inclusive fear memory engram forms and persists at a remote time point, plasticity impacting electrophysiological responses of engram neurons, not their population size, encodes fear memory and drives behavioral manifestations of long-term fear memory recall., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hammack, Fischer, Andrade and Toney.)

Severe traumatic brain injury has historically been a non-survivable injury. Recent advances in neurosurgical care, however, have demonstrated that these patients not only can survive, but they also can recover functionally when they undergo appropriate cerebral decompression within hours of injury. At the present, general surgeons are deployed further forward than neurosurgeons (Role 2 compared to Role 3) and have been provided with guidelines that stipulate conditions where they may have to perform decompressive craniectomies. Unfortunately, Role 2 medical facilities do not have access to computed tomography imaging or intracranial pressure monitoring capabilities rendering the decision to proceed with craniectomy based solely on exam findings. Utilizing a case transferred from downrange to our institution, we demonstrate the utility of a small, highly portable quantitative pupillometer to obtain reliable and reproducible data about a patient's intracranial pressures. Following the case presentation, the literature supporting quantitative pupillometry for surgical decision-making is reviewed., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2020. This work is written by (a) US Government employee(s) and is in the public domain in the US.)