Elsevier

Neuroscience

Volume 176, 10 March 2011, Pages 12-19
Neuroscience

Cellular and Molecular Neuroscience
Review
Learning and memory consolidation: linking molecular and behavioral data

https://doi.org/10.1016/j.neuroscience.2010.12.056Get rights and content

Abstract

This paper puts together and links some classic and recent molecular data and hypothesis from different authors and laboratories related to learning and memory consolidation. Mainly addressed to non-specialists, it describes how the glutamatergic activation of plastic synapses in the hippocampus can give rise to new or enlarged dendritic spines which may constitute the main structural basis of some kind of memories. To establish learning and memory, the nervous system can use part of the same mechanisms which make the basic structure of neurons during the ontogenetic development of the brain. Through different families of kinases, phosphatases and other proteins, the activated N-methyl-d-aspartate (NMDA) receptors and different intracellular signals originated in the post-synaptic membranes can promote the synthesis of new proteins and the dynamic of actin. The consecutive morphological changes in the cytoskeleton of the neuron, later stabilized by new receptors inserted in the post-synaptic membranes, make possible memory consolidation. Short and long-term, as well as persistence, of memory mechanisms are related to these molecular processes. Recent research on system consolidation and memory allocation in neural circuits is also explained.

Research highlights

▶Current research shows a complex image of mechanisms underlying memory formation. ▶ Molecular and behavioral data can be provisionally linked in an integrative approach. ▶Different families of proteins can promote memory consolidation and persistence.

Section snippets

Historical background

The Spanish Santiago Ramón y Cajal (1852–1934), whose intuition led him to infer the function of the nervous system from its morphology, was the first scientist suggesting plasticity in the number and strength of neural connections as the physical basis of learning and the support of memory (Ramón y Cajal, 1894). In 1949 the Canadian psychobiologist Donal O. Hebb (1904–1985) proposed associative plasticity as the mechanism from which coincidence in pre- and post-synaptic activity would be able

Hippocampal plasticity

Dendritic spines are branched protoplasmic extensions which are the major site of excitatory synaptic transmission in the vertebrate brain. Different authors and experimental research on the initiation and maintenance of synaptic plasticity, particularly in CA1 pyramidal neurons of the hippocampus, have shown that certain types of learning, as well as artificially induced LTP, can produce increases or morphological changes in dendritic spines giving rise to new or strengthen existing synapses

From short- to long-term memory

Short term memory (STM) is a brief retention (minutes, hours) of conscious information supported by transient or non-stabilized post-translational modification of preexisting molecules that alters the efficiency of synaptic transmission in plastic neural networks. When, as a consequence of saliency of information to be remembered, and/or repetition of experience, such changes persist, they can activate the above described machinery, producing the synthesis of new proteins and structural changes

System consolidation

Memory consolidation at synaptic level in places like the hippocampus can be followed by a more prolonged process that involves a gradual reorganization of the different brain regions that support memory. It has been suggested (Frankland and Bontempi, 2005) that the synaptic changes in the hippocampus can serve to integrate information from distributed cortical areas, each representing individual components of a memory. However, as the memory matures, connections between the different cortical

Memory allocation in neural circuits

Wherever memories are stored, it is important to know how learning selects the particular neurons and synapses where the information is allocated within a neural circuit avoiding interferences between the different memories stored throughout lifetime. This has been highlighted by recent experimental works from Silva and other researchers in UCLA. They have shown that several specific mechanisms could be involved in such selection. Thus, neurons activated by CREB during learning are more

Conclusion

Current experimental and clinical research shows a multiple and complex image of the synaptic and molecular mechanisms underlying learning and memory formation. Following different authors and laboratories, here we have tried to link some of these mechanisms together and with their related behavioral events in order to give an always partial and provisional, but somehow comprehensive, panorama of the different phases of these processes. This approach is obviously risky, but can prevent the

Acknowledgments

This research was supported by a Ministerio de Educación y Ciencia (MEC) grant (project PSI2009-07491), and a Generalitat de Catalunya grant (2009SGR).

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