Thesis of Lisa Blum-Moyse

Modelling the integration of synaptic activity by astrocytes


The neural processes that transform memories from short-term to longterm
storage are collectively known as memory consolidation. They include synaptic consolidation,
relatively rapid intra-cellular changes that stabilize synaptic potentiation, and systems consolidation,
slower and larger-scale processes that reorganize and restructure memory traces across brain systems.
In particular, systems consolidation refers to mechanisms that gradually make memories independent
of the hippocampus. The theory of memory systems consolidation posits a dual-store memory
system: a fast-learning fast-decaying hippocampus that transfers memories to slow-learning longterm
cortical storage. Hippocampal lesions interrupt this transfer, so recent memories are more
likely to be lost than more remote memories.
The recent discovery of engram cells highlighted a new comprehension of the phenomenon. An
"engram" refers to the enduring offline physical and/or chemical changes that were elicited by
learning and underlie the newly formed memory associations. Engram cells are populations of cells
that constitute critical cellular components of a given engram.
Tonegawa suggested that Systems Consolidation Memory occurs in two major steps: the rapid
generation of silent engrams in the mPFC during learning and the slow functional maturation of
these engrams, which is aided by input from hippocampal engram cells during the post-training
period. This maturation process includes augmentation of spine density in the mPFC engram cells,
which also requires input from the hippocampal engram cells. The mechanisms responsible for
maturation and de-maturation of engram cells are still unknown. Maturation of cortical engram
cells could be ensured by repeated sharp-wave ripple-mediated replay of hippocampal CA1 engram
cell activity during the animal's slow-wave sleep. Concerning de-maturation the question is whether
this is a passive process in which unused engrams undergo a progressive loss of active synapses or
an active process that ensures turnover and reuse of hippocampal cells for new memories. The
mature mPFC engram cells could have a role in this process through their back projections to the
Furthermore there is compelling evidence that sleep actively supports the formation of longlasting
memory representations. Finally, a recent paper showed that synaptic scaling (a slow process usually associated
with the maintenance of activity homeostasis) appears a viable candidate mechanism to bridge
the large temporal gap between synaptic plasticity (minutes) and synaptic consolidation (days).
Scaling operates on time scales of hours to days and synaptic plasticity on seconds to minutes. In
their framework a system can be in a short or a long-term memory state, which could respectively
correspond to the hippocampal and cortical state, depending on some parameters like the input
strength or the ratio between synaptic scaling and synaptic plasticity.
The objective of the PhD is to developed mathematical models of systems consolidation based on biophysical models of neuronal networks for the cortex, the hippocampus, and their interconnections.

Advisor: Hugues Berry