The biochemistry of memory

Abstract

Almost fifty years ago, Julius Adler initiated a program of research to gain insights into the basic biochemistry of intelligent behavior by studying the molecular mechanisms that underlie the chemotactic responses of Escherichia coli. All living organisms share elements of a common biochemistry for metabolism, growth and heredity - why not intelligence? Neurobiologists have demonstrated that this is the case for nervous systems in animals ranging from worms to man. Motile unicellular organisms such as E. coli exhibit rudimentary behaviors that can be loosely described in terms of cognitive phenomena such as memory and learning. Adler's initiative at least raised the prospect that, because of the numerous experimental advantages provided by E. coli, it would be the first organism whose behavior could be understood at molecular resolution.

Figure 1. The E. coli nanobrain

Sensory-motor regulation in motile bacteria such as E. coli involves a so-called nanobrain consisting of an array of several thousand alpha-helical transmembrane protein fibers clustered together at one pole. Receptor protein domains that specifically bind attractants such as serine, aspartate, ribose, etc. are associated with the extracytoplasmic sensory receptor input ends of these fibers, and a protein kinase that serves to control flagellar function is associated with the opposite, protein kinase output end of each fiber. The binding of attractant ligands induces changes in fiber conformation that act to control protein kinase activity and thereby modulate swimming behavior. Each of the thousands of fibers that constitute the nanobrain consists of a four-helix bundle with at least eight potentially anionic glutamate side chains that can be either exposed as a minus charge or neurtralized by methylation. Attractants induce increases in methylation (filled ovals) that counteract the effects of attractant binding and restore behavior to a preset, adapted steady state value. The new steady state level of methylation provides a memory function that acts as a reference to control further behavioral modifications. Subsequent increases (or decreases) in attractant concentration produce attractant (or repellent) behavioral responses that lead, in turn, to increases (or decreases) in methylation that act to restore steady state behavior, and provide a new baseline ‘memory’ for the assessment of future attractant or repellent stimuli.