Neuronal microcircuits for decision making in C. elegans

The simplicity and genetic tractability of the nervous system of the nematode Caenorhabditis elegans make it an attractive system in which to seek biological mechanisms of decision making. Although work in this area remains at an early stage, four basic types paradigms of behavioral choice, a simple form of decision making, have now been demonstrated in C. elegans. A recent series of pioneering studies, combining genetics and molecular biology with new techniques such as microfluidics and calcium imaging in freely moving animals, has begun to elucidate the neuronal mechanisms underlying behavioral choice. The new research has focussed on choice behaviors in the context of habitat and resource localization, for which the neuronal circuit has been identified. Three main circuit motifs for behavioral choice have been identified. One motif is based mainly on changes in the strength of synaptic connections whereas the other two motifs are based on changes in the basal activity of an interneuron and the sensory neuron to which it is electrically coupled. Peptide signaling seems to play a prominent role in all three motifs, and it may be a general rule that concentrations of various peptides encode the internal states that influence behavioral decisions in C. elegans.

Introduction

One of the primary functions of the nervous system is to make decisions that maximize evolutionary fitness in an unpredictable world. Neurobiologists investigate the neuronal mechanisms of decision making at two main levels of complexity. The simpler level, which may be called behavioral choice [1], mainly concerns the proximal causes of selecting between alternative sensory cues or behaviors. A typical experiment at this level seeks to identify the states of the nervous system that predict which of two or more mutually exclusive behaviors will be activated on each trial in a series of identical stimuli. The more complex level, which has been termed value-based decision making [2], examines not only proximal causes, but ultimate causes as well. Here, experimental conditions are arranged so that the subject's prior assessment of the relative benefits of distinct choices can be manipulated experimentally. At the neuronal level, researchers seek to understand how benefits are represented by the nervous system, and how these representations are integrated with the proximal causes of the selection between alternatives. In one simple scenario, the proximal causes of behavioral choice are the neuronal building blocks of value-based decision making. To the extent that this is so, the former serves as an important experimental model for the latter.

Historically, the neuronal analysis of decision making has emphasized humans and nonhuman primates. However, because of the difficulty of accurately manipulating the activity of functionally specific neuronal subpopulations in awake, behaving subjects, it has so far been easier to establish the neuronal correlates of decision making than its neuronal causes. Clearly, progress toward a biological theory of decision making would be accelerated by a complementary approach that studies decision making in organisms that can be genetically engineered (nematode, fruit fly, zebrafish, mouse). Such organisms are unusually amenable to optogenetic methods for activating and inactivating subpopulations of neurons, which is one of the most efficient ways to demonstrate that a particular neuronal event is necessary and sufficient for decision making. For this reason, engineerable organisms are now being used at an increasing rate in studies of decision making [3, 4].

The nematode Caenorhabditis elegans is an attractive system in which to seek biological mechanisms of decision making. Like other members of its genus, it is a so-called fruit nematode, which forages for capricious blooms of bacteria in rotting fruits, flowers, and stems [5]. Its tiny nervous system, with only 302 neurons, has been anatomically reconstructed almost completely at the ultrastructural level, yielding the celebrated ‘wiring diagram of the worm’ [6, 7]. The well-known genetic tractability of C. elegans, together with technical advances in basic nematode neurophysiology — including patch clamp electrophysiology [8], calcium imaging [9], and optical control of neuronal and muscular activity [10, 11, 12] — is accelerating the pace of research into the neuronal basis of behavior in this organism. More recently, opto-mechanical systems have been developed that enable recordings from C. elegans neurons in freely moving animals engaged in natural behaviors [13••, 14, 15, 16•]. Additionally, C. elegans uses many of the same neurotransmitters and neuromodulators as higher organisms, including dopamine and serotonin, which are involved in signaling positive and negative rewards in primate decision making [17, 18]. Thus, C. elegans is well suited for the identification of genetic, synaptic, and network-level causes of action selection that may underlie decision making in more complex organisms.