Dottorato in FARMACOLOGIA E TOSSICOLOGIA

Titolo della tesi: Memory mosaics: Navigating from hypermemory to memory disfunction, unrevealing sex-differences and brain circuits

Memory processes, intricate and multifaceted, constitute a cornerstone of cognitive function, encompassing various domains such as fear memory and episodic memory. Fear memory, a critical survival mechanism, is intricately woven into the neural fabric, involving the encoding, consolidation, and retrieval of threatening stimuli. Episodic memory, on the other hand, entails the recollection of personal experiences, embedding contextual details within the temporal framework of one's life. Despite their distinct manifestations, fear memory and episodic memory converge on shared neural substrates, including the amygdala, hippocampus and prefrontal cortex (PFC), that orchestrate the intricate dance of memory formation and retrieval. Post-Traumatic Stress Disorder (PTSD) and Alzheimer's disease (AD) represent poignant examples of memory dysfunction, albeit through divergent trajectories. PTSD, characterized by intrusive recollections and hyperarousal in response to traumatic events, underscores the dysregulation of fear memory processes. In contrast, AD unfolds as a progressive neurodegenerative disorder, marked by the insidious erosion of episodic memory and cognitive decline. Despite their disparate clinical presentations, both PTSD and AD share commonalities in terms of the challenges encountered in preclinical research. The lack of suitable animal models that faithfully recapitulate the complexities of these human conditions hampers our understanding of their underlying pathophysiology and impedes the development of effective therapeutic interventions. Despite extensive efforts to find effective treatments, for example exploring the potential of psychostimulants in preclinical and clinical studies, the elusive nature of PTSD underscores the critical need for a deeper understanding of its neurobiological underpinnings. This imperative is further emphasized by the challenges inherent in navigating the intricate landscape of PTSD research, particularly in replicating the multifaceted human pathology in preclinical models. Moreover, the disproportionate representation of males in preclinical studies overlooks essential insights into sex differences in PTSD susceptibility, urging the adoption of a more inclusive research paradigm. In this scenario, a novel perspective in memory research is fundamental and the recent discovery of individuals with Highly Superior Autobiographical Memory (HSAM) could offer new insights, since much of the focus in memory research has been on investigating normal or impaired memory capabilities. These individuals exhibit exceptional recall abilities, providing valuable discoveries into the neurobiological substrates of memory. This exploration not only enriches our understanding of memory processes but also holds promise for shedding light on memory-related disorders such as AD. In conclusion, memory stands as a cornerstone of human experience, shaping our past, present, and future. Yet, in the face of neurological and psychiatric disorders, memory can become a double-edged sword, both haunting and elusive. By bridging the gap between basic research and clinical practice, we can strive towards a deeper understanding of memory disorders and pave the way for more effective interventions that honor the complexity of human cognition.