Conference Agenda

Human memory has been classically investigated by studying individuals with average memory performance or patients with memory deficits. The discovery of individuals with a naturally enhanced type of memory, the so-called Highly Superior Autobiographical Memory (HSAM), provides the opportunity to investigate memory functions from an entirely new perspective, that might unravel the neurological foundation of enhanced memory performance. In this talk, I will review recent studies from our group that started to reveal the neurobiological mechanisms of enhanced recall in HSAM. Then, I will move on to new evidence that highlights for the first-time deficient forgetting mechanisms in HSAM. During functional magnetic resonance imaging (fMRI), 12 HSAM and 30 control subjects were presented with single words (i.e., stimulus presentation phase), each followed by a memory instruction requiring either to “remember” or “forget” the current word (i.e., active encoding/forgetting phase). Five minutes later, participants underwent an old/new memory recognition task for the previously studied (or new) words. Behaviourally, both groups showed a similar active forgetting effect, with a decreased rate of words recognized as ‘old’ when they were to be forgotten as compared to when they were to be remembered. However, at the neural level, the HSAM group showed increased activity in the dorsal and ventral frontoparietal regions during the stimulus presentation phase. Moreover, regions of the anterior and posterior midline showed increased activity during active forgetting in the HSAM vs. control group. Overall, these findings extend our current knowledge of HSAM, highlighting the existence of a mechanism related to increased stimulus elaboration and effortful stimulus suppression that might importantly contribute to this enhanced form of memory.

Enhanced memory for traumatic events is a well-recognized phenomenon, which has obvious adaptive value in evolutionary terms, as it is vital to remember dangerous situations. However, the efficient encoding of traumatic memories can, in certain conditions, become maladaptive. Severe stress often turns emotional memories into a source of chronic anxiety, which may lead to the development of stress related disorders. An appropriate emotional response to an aversive event requires fine-tuned neurotransmitter release regulation and functional neuronal circuits.

We have previously developed a rat model for PTSD-like symptomatology that allows early post-trauma behavioral profiling to enable the differentiation between susceptible and resilient phenotypes to the development of long-lasting trauma-induced behavioral alterations. However, to date, the available PTSD-like susceptible (SUS) or resilient (RES) animal models are primarily obtained based on post-trauma behavioral profiling, thus they do not allow for examination of neurobiological determinants of vulnerability (or resilience) before trauma exposure. We have now generated, by selective breeding, 2 populations of rats SUS or RES to develop PTSD-like symptoms and performed a behavioral and molecular characterization (transcriptomic analyses of fear-related brain regions) to identify markers of vulnerability and resilience to develop PTSD-like symptomatology. Data collected so far, indicated a marked distinction between the two phenotypes in terms of behavioral indices of traumatic memory (i.e., increased traumatic memory consolidation, and recall and reduced extinction in SUS vs RES) and post-trauma behavioral alterations. The availability of such SUS and RES lines of rats represents an unprecedented tool to determine mechanisms of PTSD vulnerability or resilience and identify new targets for prophylactic and/or therapeutic interventions for the treatment of trauma-related disorders.

Fear associative learning increases the chances of survival by allowing individuals to anticipate threatening events and respond pre-emptively. However, the suppression of fera memory when the danger is removed (the so-called extinction process) is crucial to permit other survival functions, and impairment in such a coping mechanism may lead to maladaptive behaviors, as in the case of trauma-related disorders. These highly debilitating conditions have immeasurable social and economic costs and affect more than 4% of the population who have witnessed traumatic events. It is classically considered that, traumatized individuals with fear symptomatology show responses that probably activate the neurobiological processes of inadequate fear inhibition (a failure in the extinction process). The ground-breaking hypothesis of this research is that in susceptible individuals the fearful event reactivates a footprint existing already before the event itself. So, trauma-related disorders may reflect neural and molecular correlates of risk, preceding the trauma. In this framework, we characterized mouse phenotypes that spontaneously show individual differences in adaptive or maladaptive fear extinction and, before the fearful experience, we found that specific morphological, electrophysiological and transcriptomic patterns of amygdala-prefrontal cortex pyramidal neurons predispose to impaired extinction. Finally, by using an optogenetic approach we showed the possibility to rescue the inefficient fear extinction activating infralimbic pyramidal neurons.