Transcriptional regulation of long-term memory in the marine snail Aplysia

Yong-Seok Lee,Craig H Bailey,Bong-Kiun Kaang,Eric R Kandel

doi:10.1186/1756-6606-1-3

Abstract

Whereas the induction of short-term memory involves only covalent modifications of constitutively expressed preexisting proteins, the formation of long-term memory requires gene expression, new RNA, and new protein synthesis. On the cellular level, transcriptional regulation is thought to be the starting point for a series of molecular steps necessary for both the initiation and maintenance of long-term synaptic facilitation (LTF). The core molecular features of transcriptional regulation involved in the long-term process are evolutionally conserved in Aplysia, Drosophila, and mouse, and indicate that gene regulation by the cyclic AMP response element binding protein (CREB) acting in conjunction with different combinations of transcriptional factors is critical for the expression of many forms of long-term memory. In the marine snail Aplysia, the molecular mechanisms that underlie the storage of long-term memory have been extensively studied in the monosynaptic connections between identified sensory neuron and motor neurons of the gill-withdrawal reflex. One tail shock or one pulse of serotonin (5-HT), a modulatory transmitter released by tail shocks, produces a transient facilitation mediated by the cAMP-dependent protein kinase leading to covalent modifications in the sensory neurons that results in an enhancement of transmitter release and a strengthening of synaptic connections lasting minutes. By contrast, repeated pulses of 5-hydroxytryptamine (5-HT) induce a transcription- and translation-dependent long-term facilitation (LTF) lasting more than 24 h and trigger the activation of a family of transcription factors in the presynaptic sensory neurons including ApCREB1, ApCREB2 and ApC/EBP. In addition, we have recently identified novel transcription factors that modulate the expression of ApC/EBP and also are critically involved in LTF. In this review, we examine the roles of these transcription factors during consolidation of LTF induced by different stimulation paradigms.

Highlights

Memory can be divided into declarative and non-declarative processes
We focus on the role of nuclear transcription factors in the presynaptic sensory neurons of Aplysia during long-term facilitation (LTF)
The depolarization-induced Aplysia the CCAAT enhancer-binding protein (ApC/EBP) induction appears to be mediated by transient induction of the nucleolar protein, ApLLP, which was recently characterized as a novel transcription factor induced by neural activity in Aplysia sensory neuron [39]

Summary

Introduction

Memory can be divided into declarative and non-declarative processes. Declarative or explicit memory is the conscious recall of knowledge about facts and events and is well developed in the vertebrate brain. The depolarization-induced ApC/EBP induction appears to be mediated by transient induction of the nucleolar protein, ApLLP, which was recently characterized as a novel transcription factor induced by neural activity in Aplysia sensory neuron [39]. When TM-apCAM was overexpressed in sensory neurons, five pulses of 5-HT failed to produce synaptic facilitation or enhancement of synaptic growth, suggesting that down-regulation of apCAM is required for both LTF and the presynaptic structural changes induced by 5-HT [53]. PKA stimulates the nuclear translocation of the retrograde signal molecule CAMAP via phosphorylating its Ser148 This phosphorylation results in both the dissociation from TM-apCAM and the restoration of its transcriptional activity from autoinhibition. ApC/EBP, which pairs with ApAF, could activate the transcription of effector genes critically involved in the consolidation and maintenance of long-term memory [36].

Kandel ER

11. Kandel ER