Reconsolidation in humans opens up declarative memory to the entrance of new information Cecilia Forcato, María L.C. Rodríguez, María E. Pedreira 1 , Héctor Maldonado * ,1 Laboratorio de Neurobiología de la Memoria, Departamento de Fisiología y Biología Molecular y Celular, IFIBYNE-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, Buenos Aires 1428, C1428EGA Buenos Aires, Argentina article info Article history: Received 9 May 2009 Revised 13 August 2009 Accepted 18 August 2009 Available online 22 August 2009 Keywords: Labilization–reconsolidation Memory updating Reminder Declarative memory Retrieval interference abstract A consolidated memory recalled by a reminder enters a vulnerability phase (labilization), followed by a process of stabilization (reconsolidation). Several authors have suggested that the labilization of the con- solidated memory makes the incorporation of new information possible. Here, we demonstrate updating in the framework of memory declarative reconsolidation in humans by giving an opportune verbal instruction. Volunteers learn an association between five cue-syllables (L1) and their respective response-syllables. Twenty-four hours later, the paired-associate verbal memory is labilized by exposing the subjects to the reminder, and then they receive the verbal Instruction of adding three new cue- response syllables (INFO) with their respective responses to the former list of five. The new information is incorporated into the single former L1-memory and both INFO and L1 are successfully retrieved on the third day. However, when the Instruction is not preceded by a proper reminder, or when the instruction omits the order of adding the INFO into the former L1-memory, we observed interference in retrieval of both the original and the new information, suggesting that they are encoded independently and coexist as separate memories. Ó 2009 Elsevier Inc. All rights reserved. 1. Introduction According to the reconsolidation hypothesis, consolidated mem- ory recalled by a reminder enters a vulnerability phase (labilization) during which it is transiently sensitive to disruption (or enhance- ment), followed by a process of stabilization that returns memory to the former state (Nader, Schafe, & LeDoux, 2000; Sara, 2000a). The reminder is the event that triggers the labilization–reconsolida- tion process of the memory. This process has been shown in very di- verse species and types of memory, including the human procedural memory of a motor skill task (Walker, Brakefield, Hobson, & Stick- gold, 2003), and reconsolidation in verbal learning (Forcato, Burgos, Argibay, Pedreira, and Maldonado, 2007). In both cases, the amnesic agent was other learning and recently, Kindt, Soeter, and Vervliet (2009) showed that oral administration of the b-adrenergic receptor antagonist propanolol disrupts the human labilization–reconsolida- tion process of a fear memory, erasing its behavioural expression 24 h later and preventing the return of fear. Since the early formulation of the reconsolidation hypothesis, several controversial items have arisen, mainly concerning the dubious functionality of positing a consolidated memory in the transient but risky stage of being labilized. Several authors pro- posed that retrieval triggers a reconsolidation process that allows the integration of new information into the background of the past (memory updating). In other words, reconsolidation would make it possible to associate new learning with already established and reactivated memories (Lewis, 1979; Nader et al., 2000; Sara, 2000b). Indeed, it seems intuitively obvious that memory needs to be continuously updated with new learning (Alberini, 2007) and some authors have studied memory updating in the frame- work of reconsolidation (Hupbach, Gomez, Hardt, & Nadel, 2007; Morris et al., 2006; Rodriguez-Ortiz, De la Cruz, Gutierrez, & Ber- mudez-Rattoni, 2005; Tronel, Milekic, & Alberini, 2005). In our first paper on reconsolidation with humans (Forcato et al., 2007) we highlighted the suitability of this model to study the role of reconsolidation in memory updating thanks to the op- tion of using a verbal instruction as a tool in the experiment. In the present paper, we address the possibility that a proper verbal instruction, given contingently upon a memory that has just been labilized by a reminder, allows us to add new information to the former memory. Based on the results of our previous papers (Forcato, Argibay, Pedreira, & Maldonado, 2009; Forcato et al., 2007), the present re- search was aimed at studying the effect of changing either the 1074-7427/$ - see front matter Ó 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.nlm.2009.08.006 * Corresponding author. Fax: +54 11 4576 3384. E-mail address: hector@fbmc.fcen.uba.ar (H. Maldonado). 1 These authors contributed equally. Neurobiology of Learning and Memory 93 (2010) 77–84 Contents lists available at ScienceDirect Neurobiology of Learning and Memory journal homepage: www.elsevier.com/locate/ynlme