Catharine H. Rankin

Habituation revisited: an updated and revised description of the behavioral characteristics of habituation.

The most commonly cited descriptions of the behavioral characteristics of habituation come from two papers published almost 40 years ago [Groves, P. M., & Thompson, R. F. (1970). Habituation: A dual-process theory. Psychological Review, 77, 419-450; Thompson, R. F., & Spencer, W. A. (1966). Habituation: A model phenomenon for the study of neuronal substrates of behavior. Psychological Review, 73, 16-43]. In August 2007, the authors of this review, who study habituation in a wide range of species and paradigms, met to discuss their work on habituation and to revisit and refine the characteristics of habituation. This review offers a re-evaluation of the characteristics of habituation in light of these discussions. We made substantial changes to only a few of the characteristics, usually to add new information and expand upon the description rather than to substantially alter the original point. One additional characteristic, relating to long-term habituation, was added. This article thus provides a modern summary of the characteristics defining habituation, and can serve as a convenient primer for those whose research involves stimulus repetition.

High-throughput behavioral analysis in C. elegans

We designed a real-time computer vision system, the Multi-Worm Tracker (MWT), which can simultaneously quantify the behavior of dozens of Caenorhabditis elegans on a Petri plate at video rates. We examined three traditional behavioral paradigms using this system: spontaneous movement on food, where the behavior changes over tens of minutes; chemotaxis, where turning events must be detected accurately to determine strategy; and habituation of response to tap, where the response is stochastic and changes over time. In each case, manual analysis or automated single-worm tracking would be tedious and time-consuming, but the MWT system allowed rapid quantification of behavior with minimal human effort. Thus, this system will enable large-scale forward and reverse genetic screens for complex behaviors.

An elegant mind: Learning and memory in Caenorhabditis elegans

This article reviews the literature on learning and memory in the soil-dwelling nematode Caenorhabditis elegans. Paradigms include nonassociative learning, associative learning, and imprinting, as worms have been shown to habituate to mechanical and chemical stimuli, as well as learn the smells, tastes, temperatures, and oxygen levels that predict aversive chemicals or the presence or absence of food. In each case, the neural circuit underlying the behavior has been at least partially described, and forward and reverse genetics are being used to elucidate the underlying cellular and molecular mechanisms. Several genes have been identified with no known role other than mediating behavior plasticity.

Dopamine Mediates Context-Dependent Modulation of Sensory Plasticity in C. elegans

Dopamine has been implicated in the modulation of diverse forms of behavioral plasticity, including appetitive learning and addiction. An important challenge is to understand how dopamines effects at the cellular level alter the properties of neural circuits to modify behavior. In the nematode C. elegans, dopamine modulates habituation of an escape reflex triggered by body touch. In the absence of food, animals habituate more rapidly than in the presence of food; this contextual information about food availability is provided by dopaminergic mechanosensory neurons that sense the presence of bacteria. We find that dopamine alters habituation kinetics by selectively modulating the touch responses of the anterior-body mechanoreceptors; this modulation involves a D1-like dopamine receptor, a Gq/PLC-beta signaling pathway, and calcium release within the touch neurons. Interestingly, the body touch mechanoreceptors can themselves excite the dopamine neurons, forming a positive feedback loop capable of integrating context and experience to modulate mechanosensory attention.

A Dynamic Network Simulation of the Nematode Tap Withdrawal Circuit: Predictions Concerning Synaptic Function Using Behavioral Criteria

The nematode tap withdrawal reflex demonstrates several forms of behavioral plasticity. Although the neural connectivity that supports this behavior is identified (Integration of mechanosensory stimuli in Caenorhabditis elegans, Wicks and Rankin, 1995, J Neurosci 15:2434–2444), the neurotransmitter phenotypes, and hence whether the synapses in the circuit are excitatory or inhibitory, remain uncharacterized. Here we use a novel strategy to predict the polarity configuration, i.e., the array of excitatory and inhibitory connections, of the nematode tap withdrawal circuit using an anatomically and physiologically justifiable dynamic network simulation of that circuit. The output of the modeled circuit was optimized to the behavior of animals, which possessed circuits altered by surgical ablation by exhaustively enumerating an array of synaptic signs that constituted the modeled circuit. All possible polarity configurations were then compared, and a statistical analysis was used to determine whether, for a given synaptic class, a particular polarity was associated with a good fit to behavioral data. The results from four related experiments were used to predict the polarities of seven of the nine cell classes of the tap withdrawal circuit. In addition, the model was used to assess possible roles for two novel mechanosensory integration neurons: DVA and PVD.

Factors affecting habituation and recovery from habituation in the nematode Caenorhabditis elegans..

In four experiments, the factors that affect the rate of habituation, the degree of habituation, and the rate of recovery from habituation in a simple reflex circuit in Caenorhabditis elegans were investigated. The results showed that habituation was more pronounced and faster, and that recovery from habituation was more rapid, with short interstimulus intervals (ISIs) than with longer ISIs. Rate of recovery differed in animals that had reached asymptotic response levels when compared with animals still in the descending portion of the habituation curve. Once animals reached asymptotic response levels, rate of recovery appeared to be determined by ISI and not by additional stimuli.

Blocking memory reconsolidation reverses memory-associated changes in glutamate receptor expression.

It has been reported that consolidated memories can return to a labile state when reactivated and undergo a process of re-storage, termed reconsolidation, required for later recall. We investigated memory for a nonassociative learning task (habituation) and found that memory for this task also undergoes reconsolidation after recall. To investigate reconsolidation, we first demonstrated that adult Caenorhabditis elegans are capable of reliable memory 48 h after habituation training (p < 0.05). When heat shock was administered immediately after a reminder, response magnitudes of trained animals matched response levels of untrained animals: the inhibitory effects of heat shock on protein synthesis disrupted memory reconsolidation. Pharmacological blockade of non-NMDA-type glutamate receptors during reminder also eliminated 48 h retention. When expression levels of a specific glutamate receptor subunit (GLR-1) (40% homology to mammalian AMPA-type glutamate receptors) (Hart et al., 1995; Maricq et al., 1995) were measured 48 h after training, there was a significant decrease in trained compared with untrained controls. If trained worms were given a reminder followed immediately by heat shock, the effect of training on GLR-1 levels was reversed. From these studies, we conclude that both the behavioral expression of long-term memory for habituation and a cellular correlate of that memory (the alteration in expression levels of GLR-1) in C. elegans can be altered after retrieval. Furthermore, conditions that impair memory consolidation similarly disrupt memory reconsolidation, suggesting that similar mechanisms are involved.

From gene to identified neuron to behaviour in Caenorhabditis elegans

Understanding the role of genes in behaviour is greatly enhanced by understanding how they affect the function of the neurons that underlie behaviour. The study of behavioural genetics in Caenorhabditis elegans, an organism with a nervous system small enough to allow the role of every neuron in a given behaviour to be known, has given researchers unique insights into how genes contribute to behaviour in general. Many have taken advantage of the unique features of this worm to analyse genes from their sequence to their role in neuronal function and, ultimately, in behaviour.

Context conditioning in habituation in the nematode Caenorhabditis elegans.

Habituation has traditionally been considered a nonassociative form of learning. However, recent research suggests that retention of this nonassociative form of learning may be aided by associations formed during training. An example of this is context conditioning, in which animals that are trained and tested in the presence of a contextual cue show greater retention than animals trained and tested in different environments. This article reports context conditioning in habituation in the nematode Caenorhabditis elegans. The results showed that retention of habituation to tap at both 10- and 60-s interstimulus intervals was significantly greater if training and testing occurred in the presence of the same chemosensory cue (NaCH3COO). This context conditioning showed both extinction and latent inhibition, demonstrating that these simple worms with only 302 neurons are capable of associative context conditioning.

Behavioral and genetic characterization of habituation using Caenorhabditis elegans

This review surveys the literature that investigates the behavioral characterization and cellular and molecular mechanisms of habituation using the model organism Caenorhabditis elegans. In 1990, C. elegans was first observed to show habituation to a non-localized mechanical tap. The parameters that govern this behavioral plasticity in C. elegans were subsequently characterized, which lead to the important hypothesis that habituation is mediated by multiple mechanisms. Many tools are available to C. elegans researchers that allow for relatively easy genetic manipulation. This has lead to a number of recent genetic studies that have begun to identify key genes and molecules that play a role in the mechanisms of habituation. Some of these genes include a vesicular glutamate transporter, a glutamate receptor subunit, a dopamine receptor and downstream intracellular signaling molecules, such as G proteins and kinases. Some of these genes only affect certain parameters of habituation, but not others supporting the hypothesis that multiple mechanisms mediate habituation. The field of research has also led to the dissection of different phases of memory (short-term vs. long-term memory for habituation), which are triggered by different training paradigms. The differences in mechanism between these various forms of memory are also beginning to be revealed.