The Role of Reconsolidation and the Dynamic Process of Long-Term Memory Formation and Storage

It is becoming increasingly clear that the processes of memory formation and storage are exquisitely dynamic. Elucidating the nature and temporal evolution of the biological changes that accompany encoding, storage, and retrieval is key to understand memory formation. For explicit or medial temporal lobe-dependent memories that form after a discrete event and are stored for a long time, the physical changes underlying the encoding and processing of the information (memory trace or engram) remain in a fragile state for some time. However, over time, the new memory becomes increasingly resistant to disruption until it is consolidated. Retrieval or reactivation of an apparently consolidated memory can render the memory labile again, and reconsolidation is the process that occurs to mediate its restabilization. Reconsolidation also evolves with the age of the memory: Young memories are sensitive to post-reactivation disruption, but older memories are more resistant. Why does a memory become labile again if it is retrieved or reactivated? Here I suggest that the main function of reconsolidation is to contribute to the lingering consolidation process and mediate memory strengthening. I also discuss the literature and results regarding the influence of the passage of time on the reconsolidation of memory. These points have important implications for the use of reconsolidation in therapeutic settings

Mechanisms of Memory Enhancement

The ongoing quest for memory enhancement is one that grows necessary as the global population increasingly ages. The extraordinary progress that has been made in the past few decades elucidating the underlying mechanisms of how long-term memories are formed has provided insight into how memories might also be enhanced. Capitalizing on this knowledge, it has been postulated that targeting many of the same mechanisms, including CREB activation, AMPA/ NMDA receptor trafficking, neuromodulation (e.g. via dopamine, adrenaline, cortisol or acetylcholine) and metabolic processes (e.g. via glucose and insulin) may all lead to the enhancement of memory. These and other mechanisms and/or approaches have been tested via genetic or pharmacological methods in animal models, and several have been investigated in humans as well. In addition, a number of behavioral methods, including exercise and reconsolidation, may also serve to strengthen and enhance memories. By capitalizing on this knowledge and continuing to investigate these promising avenues, memory enhancement may indeed be achieved in the future

Temporally Graded Requirement for Protein Synthesis following Memory Reactivation

AbstractLearning of new information is transformed into long-lasting memory through a process known as consolidation, which requires protein synthesis. Classical theory held that once consolidated, memory was insensitive to disruption. However, old memories that are insensitive to protein synthesis inhibitors can become vulnerable if they are recalled (reactivated). These findings led to a new hypothesis that when an old memory is reactivated, it again becomes labile and, similar to a newly formed memory, requires a process of reconsolidation in order to be maintained. Here, we show that the requirement for protein synthesis of a reactivated memory is evident only when the memory is recent. In fact, memory vulnerability decreases as the time between the original training and the recall increases

Introduction to the special issue on the ontogeny of hippocampal functions

No Abstract available

The Ontogeny of Hippocampus-Dependent Memories

The formation of memories that contain information about the specific time and place of acquisition, which are commonly referred to as "autobiographical" or "episodic" memories, critically relies on the hippocampus and on a series of interconnected structures located in the medial temporal lobe of the mammalian brain. The observation that adults retain very few of these memories from the first years of their life has fueled a long-standing debate on whether infants can make the types of memories that in adults are processed by the hippocampus-dependent memory system, and whether the hippocampus is involved in learning and memory processes early in life. Recent evidence shows that, even at a time when its circuitry is not yet mature, the infant hippocampus is able to produce long-lasting memories. However, the ability to acquire and store such memories relies on molecular pathways and network-based activity dynamics different from the adult system, which mature with age. The mechanisms underlying the formation of hippocampus-dependent memories during infancy, and the role that experience exerts in promoting the maturation of the hippocampus-dependent memory system, remain to be understood. In this review, we discuss recent advances in our understanding of the ontogeny and the biological correlates of hippocampus-dependent memories

Towards a Framework for a New Research Ecosystem

A major gap exists between the conceptual suggestion of how much a nation should invest in science, innovation, and technology, and the practical implementation of what is done. We identify 4 critical challenges that must be address in order to develop an environment conducive to collaboration across organizations and governments, while also preserving commercial rewards for investors and innovators, in order to move towards a new Research Ecosystem.Comment: 20 pages, 1 table, 2 figure

Insulin-like growth factor 2 (IGF-2) rescues social deficits in NLG3–/y mouse model of ASDs

Autism spectrum disorders (ASDs) comprise developmental disabilities characterized by impairments of social interaction and repetitive behavior, often associated with cognitive deficits. There is no current treatment that can ameliorate most of the ASDs symptomatology; thus, identifying novel therapies is urgently needed. Here, we used the Neuroligin 3 knockout mouse (NLG3–/y), a model that recapitulates the social deficits reported in ASDs patients, to test the effects of systemic administration of IGF-2, a polypeptide that crosses the blood-brain barrier and acts as a cognitive enhancer. We show that systemic IGF-2 treatment reverses the typical defects in social interaction and social novelty discrimination reflective of ASDs-like phenotypes. This effect was not accompanied by any change in spontaneous glutamatergic synaptic transmission in CA2 hippocampal region, a mechanism found to be crucial for social novelty discrimination. However, in both NLG3+/y and NLG3–/y mice IGF-2 increased cell excitability. Although further investigation is needed to clarify the cellular and molecular mechanisms underpinning IGF-2 effect on social behavior, our findings highlight IGF-2 as a potential pharmacological tool for the treatment of social dysfunctions associated with ASDs