Model and remodel the trace: actin cytoskeleton?s role in different memory processes

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

San Diego, California

Congreso; Society for Neuroscience Annual Meeting; 2018

SfN

Memory consolidation is the process by which new information is encoded in a stable form in neural circuits. Once a memory is already consolidated, certain types of reminders of the learning event (i.e. a short re-exposure to the training context) might induce memory labilization and a process of reconsolidation is required to re-stabilize the memory trace. When the reminder of the learning event is prolonged in time, an extinction memory may form, consisting in a new memory trace which temporarily inhibits the expression of the original one. Long-term memory has been associated with morphological changes in the brain, in strict correlation with changes in synaptic efficacy. Such plasticity is proposed to rely on dendritic spines as a sort of neuronal canvas on which these changes can take place. 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. Depolymerization of actin cytoskeleton is mainly regulated by a family of actin-binding proteins termed ADF/cofilin, becoming an attractive target to study processes underlying dendritic plasticity. Using a contextual fear conditioning paradigm in mice, we have found that pharmacological induction of depolymerization of actin filaments through an intra-hippocampal injection of BMS-5 ?a potent inhibitor of LIM kinase, which is in turn an inhibitor of ADF/Cofilin activity? causes an impairment in memory consolidation and reconsolidation. On the other hand, when favoring stabilization of actin filaments by intra-hippocampal injection of Jasplakinolide immediately before a reminder session that usually elicits reconsolidation of memory, the consolidation of an extinction memory was facilitated. Moreover, extinction was impaired when direct actin cytoskeleton depolymerization was induced by intra-hippocampal administration of Latrunculin-A immediately after a prolonged reminder session. In addition, western blot analysis of synaptoneurosome-enriched hippocampal fraction obtained after a short reminder session that leads to reconsolidation showed an increased P-Cofilin/Cofilin ratio, implying a diminished depolymerization activity by this factor, therefore favoring stabilization of actin filaments. All of these results support the role of actin cytoskeleton dynamics in the morphological changes which underlie different memory processes.