Federica Lareno Faccini
Hippocampo-cortical dynamics underlying memory formation and consolidation
The two-stage model of memory trace formation posits that the hippocampus is responsible for the quick but volatile encoding of a memory trace. During subsequent sleep, such newly encoded memory traces are transferred to the neocortex for long-term storage. This mechanistic model was initially formulated by Buzsaki in 1989 and proposed a role for ripples (high frequency oscillations taking place in the hippocampus, during sleep and quiet wakefulness) in the consolidation phase. Further support to this model was given by the discovery of replays, the neuronal content of ripples, where sequences of place cells (space modulated cells) activated during exploration are reactivated in the same order but compressed in time.
For two decades, direct causal evidence to confirm such a model was lacking. Our lab has helped to demonstrate the key role hippocampal activity plays in both encoding and consolidation of spatial and episodic memory. One main question regarded the mechanism underlying the encoding of the sequences of place cells during exploration. By dynamically modulating the ability of the rat to walk, while being moved on a model train, we were able to show that the fine tuning of the sequences at the theta, 7-12Hz, timescale (theta sequences), and not at the behavioural timescale, was needed for the generation of replays. We also showed the role of ripples in the consolidation of memory traces, by disrupting their natural occurrence during sleep after a spatial memory task. This was obtained by a closed-loop electrical stimulation of online detected ripples. The team investigated also the hippocampal-prefrontal pathway and its role in consolidation of spatial and episodic memory. We enhanced the synchrony of ripples (hippocampal activity) and delta waves and spindles (neocortical and thalamo-cortical activity, respectively) during sleep after a behavioural task, designed to promote encoding but not consolidation. Behavioural performance was increased in subsequent trials and the prefrontal local network underwent functional reorganisation. This demonstrated the importance of the hippocampo-prefrontal pathway in memory consolidation. Lastly, we have investigated the nature of delta waves (down state of cortical slow oscillations). They have been historically considered as periods of general silence of the neocortical network. But upon close inspection, a small number of residual spikes was detected and we demonstrated that these neurons were part of neuronal assemblies functionally linked with hippocampal neurons reactivated during replays. We thus hypothesised that delta waves are needed to increase the signal-to-noise ratio of specific neuronal assemblies and facilitate consolidation of newly acquired memory traces.
In conclusion, we have shown how the hippocampus plays a crucial role in the encoding of memory traces by means of theta sequences and in their consolidation through replays and the hippocampo-cortical connections that induce plastic reorganisation of the neocortical network.
Federica Lareno Faccini studied neuroscience at the Università degli studi di Trieste, Italy where she investigated the interactions between neurons and carbon-based nanomaterialsin vitro, in the group of Laura Ballerini at SISSA.
She completed her PhD at the Institut des Neurosciences Cellulaires et Intégratives (INCI) in Strasbourg, under the supervision of Philippe Isope. During this period, she studied the role of the cerebello-prefrontal network in implicit time perception in mice. She aided in the establishment of a new experimental axis in the laboratory, for extracellular recordings and optogenetic stimulation in behaving mice.
She joined the team of Michaël Zugaro at the Collège de France in 2022 as a postdoctoral researcher, where she is specializing in data analysis of hippocampal electrophysiological signals.
Her current research is focused on the neural mechanisms under lying the formation and consolidation of episodic and spatial memory in rats.