  In long-term potentiation (LTP), one of the most studied types of neural
plasticity, synaptic strength is persistently increased in response to
stimulation. Although a number of different proteins have been implicated in
the sub-cellular molecular processes underlying induction and maintenance of
LTP, the precise mechanisms remain unknown. A particular challenge is to
demonstrate that a proposed molecular mechanism can provide the level of
stability needed to maintain memories for months or longer, in spite of the
fact that many of the participating molecules have much shorter life spans.
Here we present a computational model that combines simulations of several
biochemical reactions that have been suggested in the LTP literature and show
that the resulting system does exhibit the required stability. At the core of
the model are two interlinked feedback loops of molecular reactions, one
involving the atypical protein kinase PKM{\zeta} and its messenger RNA, the
other involving PKM{\zeta} and GluA2-containing AMPA receptors. We demonstrate
that robust bistability - stable equilibria both in the synapse's potentiated
and unpotentiated states - can arise from a set of simple molecular reactions.
The model is able to account for a wide range of empirical results, including
induction and maintenance of late-phase LTP, cellular memory reconsolidation
and the effects of different pharmaceutical interventions.
