Abstract
The ability to form long-lasting memories is critical to survival and thus is highly conserved across the animal kingdom. By virtue of its complexity, this same ability is vulnerable to disruption by a wide variety of neuronal traumas and pathologies. To identify effective therapies with which to treat memory disorders, it is critical to have a clear understanding of the cellular and molecular mechanisms which subserve normal learning and memory. A significant challenge to achieving this level of understanding is posed by the wide range of distinct temporal and spatial profiles of molecular signaling induced by learning-related stimuli. In this review we propose that a useful framework within which to address this challenge is to view the molecular foundation of long-lasting plasticity as composed of unique spatial and temporal molecular networks that mediate signaling both within neurons (such as via kinase signaling) as well as between neurons (such as via growth factor signaling). We propose that evaluating how cells integrate and interpret these concurrent and interacting molecular networks has the potential to significantly advance our understanding of the mechanisms underlying learning and memory formation.
Highlights
The ability to form long-lasting memories is an evolutionarily conserved phenomenon that is critical to survival, and the dynamic process of acquiring and storing memories is often compromised in psychiatric and neurodegenerative disorders
It is widely appreciated that learning-related stimuli induce molecular signaling cascades in discrete temporal and spatial profiles dictated by the nature of the stimulus, and these profiles are of critical importance to the resulting functional outcome
Prolonged stimulation that leads to transcription-dependent long-term synaptic facilitation (LTF) and long-term memory (LTM) in Aplysia results in a more persistent increase in cyclic adenosine monophosphate (cAMP) levels and protein kinase (PKA) activation, causing the catalytic subunit of PKA to translocate into the nucleus where it phosphorylates transcription factors important for inducing new gene expression required for long-term plasticity, including cAMP response element binding protein (CREB)-1 [58,59,60]
Summary
The ability to form long-lasting memories is an evolutionarily conserved phenomenon that is critical to survival, and the dynamic process of acquiring and storing memories is often compromised in psychiatric and neurodegenerative disorders. The study of long-lasting plasticity underlying memory formation has served as a valuable platform for the analysis of several novel molecular mechanisms, including long-term DNA modification [6] and reconsolidation [7]. A second challenge lies in the spatial regulation required by the molecular mechanisms underlying LTMs. LTM uniquely requires new gene expression, which raises the critical question as to how the synapse, where neural communication initially occurs, and the cell body, where transcription occurs, effectively communicate. We will first introduce the concept of spatial and temporal molecular networks in the context of learning and memory by reviewing the spatial and temporal profiles of selected molecular signaling cascades critical for long-lasting plasticity and LTM formation. We will discuss how neurons might integrate and interpret these concurrent and interacting molecular networks, and how this overall framework can inform the study of LTM function and dysfunction
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