Reconsolidation is a putative neuronal process in which the retrieval of a previously consolidated memory returns it to a labile state that is once again subject to stabilization. This study explored the idea that reconsolidation occurs in spatial memory when animals retrieve memory under circumstances in which new memory encoding is likely to occur. Control studies confirmed that intrahippocampal infusions of anisomycin inhibited protein synthesis locally and that the spatial training protocols we used are subject to overnight protein synthesis-dependent consolidation. We then compared the impact of anisomycin in two conditions: when memory retrieval occurred in a reference memory task after performance had reached asymptote over several days; and after a comparable extent of training of a delayed matching-to-place task in which new memory encoding was required each day. Sensitivity to intrahippocampal anisomycin was observed only in the protocol involving new memory encoding at the time of retrieval.

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The N-methyl-D-aspartate (NMDA) receptor, a subtype of excitatory amino acid receptor, mediates synaptic responses in many regions of the central nervous system. This receptor plays a critical role in the mechanisms of both synaptic plasticity and excitotoxicity. Although these receptors were generally thought to be a single homogeneous receptor population, we report observations indicating that two anatomically distinct forms of the NMDA-receptor complex exist. buffer, pH 7.0, preincubated at 30°C for 10 min, and then incubated for 10 min in ice-cold buffer containing 100 nM L-[3H]glutamate. NMDA receptors were selectively labeled by the inclusion of 100 ,uM 4-acetamido-4'-isothiocyanoatostilbene-2,2'-disulfonic acid, 5 ,uM amino-3-hydroxy-5-methylisoxazole-4-propionic acid, and 1 ,M kainic acid, which displace all detectable non-NMDA-receptor binding. Under these conditions the specific binding is fully displaced by NMDA agonists and antagonists at concentrations appropriate for NMDA receptors (12)(13)(14)(15)(16)(17)(18).Sections were then rinsed for 30 s, air dried, and placed against tritium-sensitive film along with tritium standards. Tissue sections in the experiments described in Fig. 2 9836The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Electrophysiological studies indicate the existence of several types of receptors for excitatory amino acids. Thus, responses induced by N-methyl-D-aspartate (NMDA) are potently and selectively blocked by D(-)-2-amino-5-phosphonopentanoic acid (D-AP5), while responses induced by such agonists as kainate and quisqualate are relatively resistant to this antagonist. Evidence is mounting that excitatory amino acid receptors are involved in synaptic excitation in many regions of the central nervous system (see refs 1 and 4 for reviews). Although the identity of the transmitter(s) acting at these receptors remains uncertain, L-aspartate has been considered the most likely transmitter at NMDA receptors and L-glutamate at kainate/quisqualate receptors. Other endogenous acidic amino acids proposed as possible transmitters include a range of sulphur-containing amino acids and the tryptophan metabolite, quinolinic acid. Ligand-binding studies offer a means not only of assessing receptor densities in different brain regions but also of comparing affinities of transmitter candidates for these receptors. However, to avoid difficulties of interpretation arising from the use of ligands which bind to more than one type of receptor, such as [3H]-L-glutamate and [3H]-L-aspartate (for example, refs 8-12), ligands with high receptor selectivity are required. Here, we report that [3H]-D-AP5 binds specifically to rat brain membranes, that the hippocampus and cerebral cortex are enriched in these sites relative to other brain areas and that L-glutamate has higher affinity for these receptors than have all other transmitter candidates tested.