Role of actin cytoskeleton dynamics and its modulator Cofilin 1 in fear memory processing

MEDINA, CANDELA; DE LA FUENTE, VERÓNICA; ROMANO, ARTURO

Villa Carlos Paz, Córdoba

Congreso; XXXIV Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; 2019

Sociedad Argentina de Investigación en Neurociencias

Synaptic efficacy modulation, in tight relationship with synaptic morphological changes, is proposed to underlie long-term memory processing. Such plasticity is known to occur in dendritic spines. These small actin-rich protrusions from dendrites provide a suitable biochemical compartment to locally control and integrate different inputs, due to spatial confinement. Therefore, spine number, morphology and underlying actin polymerization level can modulate synaptic efficacy in many different ways. Actin cytoskeleton has major regulating factors of its depolymerization such as Cofilin 1 (Cfl1), becoming an attractive target to study processes underlying dendritic plasticity. Using a contextual fear conditioning paradigm in mice, we found that pharmacological induction of depolymerization of actin filaments through the inhibition of LIM kinase, which is in turn an inhibitor Cfl1 activity, causes an impairment in memory reconsolidation, as well as in memory consolidation. On top of that, Cfl1 activity is inhibited and its mRNA is downregulated in CA1 neuropil after re-exposure to the training context. Moreover, by pharmacological disruption of actin cytoskeleton dynamics, the process of memory extinction can either be facilitated or impaired.