Silent learning

Contains fulltext : 200389.pdf (publisher's version ) (Closed access)We introduce the concept of "silent learning"-the capacity to learn despite neuronal cell-firing being largely absent. This idea emerged from thinking about dendritic computation [1, 2] and examining whether the encoding, expression, and retrieval of hippocampal-dependent memory could be dissociated using the intrahippocampal infusion of pharmacological compounds. We observed that very modest enhancement of GABAergic inhibition with low-dose muscimol blocked both cell-firing and the retrieval of an already-formed memory but left induction of long-term potentiation (LTP) and new spatial memory encoding intact (silent learning). In contrast, blockade of hippocampal NMDA receptors by intrahippocampal D-AP5 impaired both the induction of LTP and encoding but had no effect on memory retrieval. Blockade of AMPA receptors by CNQX impaired excitatory synaptic transmission and cell-firing and both memory encoding and retrieval. Thus, in keeping with the synaptic plasticity and memory hypothesis [3], the hippocampal network can mediate new memory encoding when LTP induction is intact even under conditions in which somatic cell-firing is blocked

The Role of the Entorhinal Cortex in Extinction: Influences of Aging

The entorhinal cortex is perhaps the area of the brain in which neurofibrillary tangles and amyloid plaques are first detectable in old age with or without mild cognitive impairment, and very particularly in Alzheimer's disease. It plays a key role in memory formation, retrieval, and extinction, as part of circuits that include the hippocampus, the amygdaloid nucleus, and several regions of the neocortex, in particular of the prefrontal cortex. Lesions or biochemical impairments of the entorhinal cortex hinder extinction. Microinfusion experiments have shown that glutamate NMDA receptors, calcium and calmodulin-dependent protein kinase II, and protein synthesis in the entorhinal cortex are involved in and required for extinction. Aging also hinders extinction; it is possible that its effect may be in part mediated by the entorhinal cortex

Retrieval induces hippocampal-dependent reconsolidation of spatial memory

Nonreinforced retrieval can cause extinction and/or reconsolidation, two processes that affect subsequent retrieval in opposite ways. Using the Morris water maze task we show that, in the rat, repeated nonreinforced expression of spatial memory causes extinction, which is unaffected by inhibition of protein synthesis within the CA1 region of the dorsal hippocampus. However, if the number of nonreinforced retrieval trials is insufficient to induce long-lasting extinction, then a hippocampal protein synthesis-dependent reconsolidation process recovers the original memory. Inhibition of hippocampal protein synthesis after reversal learning sessions impairs retention of the reversed preference and blocks persistence of the original one, suggesting that reversal learning involves reconsolidation rather than extinction of the original memory. Our results suggest the existence of a hippocampal protein synthesis-dependent reconsolidation process that operates to recover or update retrieval-weakened memories from incomplete extinction

On the role of hippocampal protein synthesis in the consolidation and reconsolidation of object recognition memory

Upon retrieval, consolidated memories are again rendered vulnerable to the action of metabolic blockers, notably protein synthesis inhibitors. This has led to the hypothesis that memories are reconsolidated at the time of retrieval, and that this depends on protein synthesis. Ample evidence indicates that the hippocampus plays a key role both in the consolidation and reconsolidation of different memories. Despite this fact, at present there are no studies about the consequences of hippocampal protein synthesis inhibition in the storage and post-retrieval persistence of object recognition memory. Here we report that infusion of the protein synthesis inhibitor anisomycin in the dorsal CA1 region immediately or 180 min but not 360 min after training impairs consolidation of long-term object recognition memory without affecting short-term memory, exploratory behavior, anxiety state, or hippocampal functionality. When given into CA1 after memory reactivation in the presence of familiar objects, ANI did not affect further retention. However, when administered into CA1 immediately after exposing animals to a novel and a familiar object, ANI impaired memory of both of them. The amnesic effect of ANI was long-lasting, did not happen after exposure to two novel objects, following exploration of the context alone, or in the absence of specific stimuli, suggesting that it was not reversible but was contingent on the reactivation of the consolidated trace in the presence of a salient, behaviorally relevant novel cue. Our results indicate that hippocampal protein synthesis is required during a limited post-training time window for consolidation of object recognition memory and show that the hippocampus is engaged during reconsolidation of this type of memory, maybe accruing new information into the original trace