C. Paraciani, MSc
Research interests
PhD thesis: 'Lost' to sleep loss: Mechanisms and strategies to reverse sleep deprivation-induced amnesia (2026)
Sleep is a conserved biological process essential for
physiological homeostasis and cognitive function, particularly
memory consolidation. While memory acquisition and retrieval occur
during wakefulness, consolidation (the stabilization and
integration of newly encoded information) primarily takes place
during sleep. Sleep deprivation (SD), increasingly prevalent in
modern society, disrupts this process, impairing memory at
behavioral, structural, and molecular levels. However, whether SD
leads to permanent memory loss or merely impairs access to stored
information remains unclear.
This thesis investigates the effects of SD on memory, memory
engrams and their retrievability. In Chapter 2, pharmacological and
optogenetic approaches demonstrate that SD-induced amnesia reflects
impaired retrieval rather than erasure of memory traces.
Restoration of memory performance via engram reactivation or
modulation of the cAMP-PKA-CREB signaling pathway indicates that
stored information remains accessible under appropriate conditions.
Chapter 3 extends this analysis to the whole-brain level,
identifying network-level disruptions associated with SD.
Functional connectivity analyses reveal key brain regions involved
in memory retrieval deficits, while interventions targeting
cGMP-PKG signaling with the FDA-approved drug vardenafil
successfully rescue memory function. These improvements correlate
with restored reactivation of dentate gyrus engram cells,
highlighting their central role in memory accessibility. Finally,
Chapter 4 addresses sex differences in sleep and memory,
emphasizing the underrepresentation of female subjects in SD
research and the modulatory role of ovarian hormones.
Together, these findings suggest that SD primarily disrupts memory
retrievability, not storage, and identify potential therapeutic
strategies to mitigate its cognitive consequences.
