Abstract:
Neocortical memory engrams are thought to mature via strengthened interconnectivity, yet synaptic plasticity alone cannot explain the dynamic vividness of enduring memories. Neuronal intrinsic excitability (IE) plasticity has been touted as an early priming mechanism that renders engram neurons susceptible to ongoing plastic processes and later encoding events. Here, we reveal that learning-induced IE plasticity of nascent anterior cingulate cortex (ACC) engram neurons is a permissive mechanism for the formation and specificity of remote memories. Using c-fos-dependent genetic/viral targeting in mice, we found that contextual fear learning triggered a time-limited increase in ACC engram IE during the early phase of memory formation. Remarkably, chemogenetically hyperpolarizing these neurons within-but not outside-the IE plasticity window strengthened consolidated memories, enhanced their context-precision, and prevented interference-induced engram reallocation. Thus, IE plasticity in nascent ACC engram neurons acts as an essential tagging mechanism that determines the fate and dynamic content of remote memories.

Abstract:
Neurocognitive impairment (NCI) is one of the most relevant clinical manifestations of multiple sclerosis (MS). The profile of NCI and the structural and functional changes in the brain structures relevant for cognition in MS share some similarities to those in Alzheimer's disease (AD), the most common cause of neurocognitive disorders. Additionally, despite clear etiopathological differences between MS and AD, an accumulation of effector/memory CD8+ T cells and CD8+ tissue-resident memory T (Trm) cells in cognitively relevant brain structures of MS/AD patients, and higher frequency of effector/memory CD8+ T cells re-expressing CD45RA (TEMRA) with high capacity to secrete cytotoxic molecules and proinflammatory cytokines in their blood, were found. Thus, an active pathogenetic role of CD8+ T cells in the progression of MS and AD may be assumed. In this mini-review, findings supporting the putative role of CD8+ T cells in the pathogenesis of MS and AD are displayed, and putative mechanisms underlying their pathogenetic action are discussed. A special effort was made to identify the gaps in the current knowledge about the role of CD8+ T cells in the development of NCI to 'catalyze' translational research leading to new feasible therapeutic interventions.

Abstract:
Post-learning hippocampal sharp wave-ripples (SWRs) generated during slow wave sleep are thought to play a crucial role in memory formation. While in Alzheimer's disease, abnormal hippocampal oscillations have been reported, the functional contribution of SWRs to the typically observed spatial memory impairments remains unclear. These impairments have been related to degenerative synaptic changes produced by soluble amyloid beta oligomers (Abetaos) which, surprisingly, seem to spare the SWR dynamics during routine behavior. To unravel a potential effect of Abetaos on SWRs in cognitively-challenged animals, we submitted vehicle- and Abetao-injected mice to spatial recognition memory testing. While capable of forming short-term recognition memory, Abeta mice exhibited faster forgetting, suggesting successful encoding but an inability to adequately stabilize and/or retrieve previously acquired information. Without prior cognitive requirements, similar properties of SWRs were observed in both groups. In contrast, when cognitively challenged, the post-encoding and -recognition peaks in SWR occurrence observed in controls were abolished in Abeta mice, indicating impaired hippocampal processing of spatial information. These results point to a crucial involvement of SWRs in spatial memory formation and identify the Abeta-induced impairment in SWRs dynamics as a disruptive mechanism responsible for the spatial memory deficits associated with Alzheimer's disease.