This blockade will include the proteins required for the synaptic restructuring necessary for memory consolidation, such as the cell-adhesion molecules (Mileusnic et al. h later, produce lasting amnesia for the task (Davis and Squire 1984; Rose 2000). Beyond this Efonidipine hydrochloride time, the memory is insensitive to the inhibitors and has been regarded as permanent (long-term memory). However, recently reconfirmed older observations show that reminding the animal of the previously learned experience renders the memory labile once more (Sara 2000a,b; Nader 2003; Dudai 2004). Administration of protein synthesis inhibitors in association with the reminder for an aversive experience produces amnesia for the task, in some cases apparently permanent (Nader et al. 2000; Nader 2003), in others more transient (Litvin and Anokhin 2000; Milekic and Alberini 2002; Eisenberg and Dudai 2004). This has prompted an ongoing debate, i.e., is the amnesia due to a blockade of the same biochemical cascade as is involved in the initial consolidation (hence, permanently preventing reconsolidation), or does it represent a temporary failure to access the memory (retrieval) (Nadel and Land 2000; Alberini 2005). Of course, in some senses this distinction is artificial, as any reminder inevitably constitutes a new experience and will involve some learning, which may be part of a process leading to extinction of the earlier memory (Vianna et al. 2001). A further complexity Efonidipine hydrochloride is added by the fact that even without reminder, putative memory traces are not entirely stable, migrating from one brain region to others over a period that may vary from hours to weeks (Myers and Davis 2002; Tronel and Sara 2002; Frankland and Bontempi 2005). Our laboratory has been studying these phenomena using a one-trial passive avoidance task in young chicks and the protein synthesis inhibitor anisomycin (Ani) (Anokhin et al. MAPKAP1 2002; Salinska et al. 2004). Ani administered around the time of reminder produces a transient amnesia for the passive avoidance response, but both the dose and the temporal dynamics of the effect are different from those producing amnesia in the hours following initial training. Furthermore, whereas the biochemical locus of change Efonidipine hydrochloride following training is in the intermediate medial mesopallium (IMMP, previously called IMHV) (Reiner et Efonidipine hydrochloride al. 2004), following a reminder it is in the region we had earlier (Rose 2000) identified as a putative storage site for the memory trace, the medial striatum (MS; previously called LPO). One explanation for the differences in the amnestic effect of Ani could be that while the initial learning experience involves enhanced gene expression and somatic protein synthesis followed by the transport of the newly synthesized proteins to the synapse, re-evoking the experience by way of a reminder engages only local (dendritic/synaptic) protein synthesis. That such synthesis can occur in dendritic spines and presynaptic elements (synaptoneurosomes) is well established Efonidipine hydrochloride (Steward and Worley 2002; Tang and Schuman 2002). We reasoned that if this were the case, then while transiently blocking axonal and dendritic flow during consolidation should result in amnesia for the task, this would not be the case following recall of the experience. Such a transient blockade, lasting minutes to hours, occurs if microtubular structure is disrupted, which can be achieved by administration of Colchicine (Borisy and Taylor 1967a; Edson et al. 1993). In the experiments reported here we have examined the effects of Colchicine on recall for the passive avoidance task following both training and reminder. Results Colchicine effect on recall following training We began by replicating and extending an earlier study by Bell and Morgan (1981). These authors reported that bilateral injections of 5g (15 nmol) Colchicine into the forebrain shortly after training resulted in a transient amnesia.