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

MEDINA C; DE LA FUENTE V; ROMANO A

Villa Carlos Paz, Córdoba

Congreso; XXXIV Reunión 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 underlielong-term memory processing. Such plasticity is known to occur in dendritic spines. These small actin-richprotrusions from dendrites provide a suitable biochemical compartment to locally control and integratedifferent inputs, due to spatial confinement. Therefore, spine number, morphology and underlying actinpolymerization level can modulate synaptic efficacy in many different ways. Actin cytoskeleton has majorregulating factors of its depolymerization such as Cofilin 1 (Cfl1), becoming an attractive target to studyprocesses underlying dendritic plasticity. Using a contextual fear conditioning paradigm in mice, we found thatpharmacological induction of depolymerization of actin filaments through the inhibition of LIM kinase, which isin turn an inhibitor Cfl1 activity, causes impairment in memory reconsolidation, as well as in memoryconsolidation. On top of that, Cfl1 activity is inhibited and its mRNA is downregulated in CA1 neuropil after reexposure to the training context. Moreover, by pharmacological disruption of actin cytoskeleton dynamics, theprocess of memory extinction can either be facilitated or impaired.