CREB and neuronal selection for memory trace

Abstract

Despite considerable progress over the past several decades, our understanding of the mechanisms underlying memory encoding, storage, and expression in a complex neural network are far from complete. In particular, how some neurons rather than others are selectively engaged to encode memory remains largely unknown. Using virus-mediated gene delivery into a small subset of neurons in a given network, molecular imaging of neuronal activity, pharmacological perturbation of specific neurons' activity and animal behavior assays, recent studies have begun to provide insight into molecular and cellular mechanisms responsible for the selection of neurons for inclusion into a memory trace. Here, we focus on a review of recent findings supporting the hypothesis that the level of the transcription factor CREB (cAMP/Ca2+-response element binding protein) is a key factor governing which neurons are recruited to a given memory trace. These recent findings open a new perspective on memory trace at the neural circuit level and also raise many important questions. Future studies employing more advanced neurobiological techniques for targeting defined populations of neurons and manipulating their activity in time and space in a complex neural network will give answers to these newly emerging questions and extend our understanding of the neurobiological basis of the memory trace.

High-throughput optical quantification of mechanosensory habituation reveals neurons encoding memory in Caenorhabditis elegans

“…Recently, there has been significant progress in identifying the neuronal substrates of memory in the brain (5,30,31). Nonetheless, it remains difficult to analyze the molecular basis of memory formation, even in cases where the responsible neurons have been identified, as the mammalian nervous system is highly complex and cell-specific genetic analysis is often difficult.…”

“…Using the developed system, we tried to address which neurons within the mechanosensory neural circuit are involved in memory formation. We focused on the C. elegans CREB homolog CRH-1, because CREB phosphorylation is a key factor in determining which neurons are recruited to a given memory trace (5,17,19,23,24). Previous studies have revealed that worms carrying a loss-of-function mutation in crh-1 exhibit a defect in mechanosensory habituation (8,17).…”

“…Recent studies have revealed that the transcription factor cAMP response element-binding protein (CREB) (1) is crucial for determining which neurons in the lateral amygdala participate in encoding an auditory fear memory, and that neurons with higher CREB activity are preferentially allocated into a unique memory trace (memory engram) (2)(3)(4)(5)(6). Thus, it has been generally thought through the accumulated weight of evidence that memory is represented by a specific population of neurons in the brain that forms memory engrams: only a portion of eligible neurons are recruited into a specific memory.…”

“…Thus, it has been generally thought through the accumulated weight of evidence that memory is represented by a specific population of neurons in the brain that forms memory engrams: only a portion of eligible neurons are recruited into a specific memory. Although this CREB-dependent memory allocation model is established (5), the identification of specific neurons supporting a given memory remains a long-standing challenge. Moreover, the extreme complexity of nervous systems in model animals still hampers cell-specific genetic analyses; therefore, even if neurons encoding memory could be identified, it would be difficult to address the subsequent question of how these neurons store memory at the molecular level in situ.…”

Basic Elements of Signal Transduction Pathways Involved in Chemical Neurotransmission

“…CREB is one of the transcription factors best associated to learning and memory (Kim et al, 2013). It has been largely probed that CREB transcription factor is fundamental for long-term memory consolidation.…”