Chapter 8 - Biochemical Mechanisms for Long-Term Information Storage at the Cellular Level

Abstract

This chapter discusses the mechanisms unique to inducing and maintaining the long-lasting, late phase of long-term potentiation (LTP). The late phase of LTP (L-LTP) is defined in terms of the protein synthesis-dependent form of synaptic potentiation in area CA1. The particular mechanisms that are being worked out to explain L-LTP are likely to have impact far beyond understanding L-LTP at Schaffer/collateral and perforant-path synapses. This area of LTP research is frequently discussed as an analogue of long-term memory as opposed to being limited to a description of a specific neuronal plasticity phenomenon. This chapter provides a brief overview of the data indicating that altered gene expression becomes manifest at just the appropriate synapse, looking at Arc mRNA as a prototype molecule. The chapter discuses N-Methyl-D-aspartate (NMDA) receptor coupling to the genome and the receptor-effector coupling mechanisms in the context of transcriptional regulation. The chapter discusses some identified gene targets in L-LTP and the issue of the way the products of these genes get to the right synapses. The chapter examines the read-outs of altered expression of these target genes—suggesting that these changes mediate structural and morphological changes in neurons. The altered expression of gene products gets translated into structural changes at the synaptic spine and altered connectivity of the neuron. Ultimately these changes are manifested as changes in the synaptic circuit in which the neuron resides. The chapter explores the induction mechanisms of L-LTP and the way a triggering calcium signal gets converted into a genomic read-out.