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Habituation is a ubiquitous form of non-associative learning observed as a decrement in responding to repeated stimulation that cannot be explained by sensory adaptation or motor fatigue. One of the defining characteristics of habituation is its sensitivity to the rate at which training stimuli are presented--animals habituate faster in response to more rapid stimulation. The molecular mechanisms underlying this interstimulus interval (ISI)-dependent characteristic of habituation remain unknown. In this article, we use behavioural neurogenetic and bioinformatic analyses in the nematode Caenorhabiditis elegans to identify the first molecules that modulate habituation in an ISI-dependent manner. We show that the Caenorhabditis elegans orthologues of Ca2+ calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs. In addition, both cmk-1 and ogt-1 mutants display a raremechanosensory hyper-responsive phenotype (i.e. larger mechanosensory responses than wild-type).Overall, our work identifies two conserved genes that function in sensory neurons to modulate habituation in an ISI-dependent manner, providing the first insights into the molecular mechanisms underlying the universally observed phenomenon that habituation has different properties when stimuli are delivered at different rates. [ABSTRACT FROM AUTHOR]

We investigated the role of the Caenorhabditis elegans CREB (cAMP response element binding protein) homologue, crh-1, in response to tap (nonlocalized mechanosensory stimulation) and tap habituation. Worms with a loss-of-function mutation in crh-1 performed smaller reversals in response to tap than did wild-type worms and did not show long-term memory for spaced training 24-hr posttraining; however, they did show short-term habituation to tap stimuli when stimuli were presented at both 10-s and 60-s interstimulus intervals, and showed 12-hr intermediate memory for spaced habituation training (intermediate-term memory). Expressing CRH-1 broadly throughout the nervous system and in a subset of interneurons of the tap withdrawal circuit, but not in the mechanosensory neurons, rescued the long-term memory defects observed in crh-1 mutants. Here we show for the first time that CREB is required for long-term habituation and show that the interneurons of the tap withdrawal response circuit are the locus of plasticity for long-term mechanosensory habituation in C. elegans. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

This review outlines research into the cellular and molecular mechanisms underlying a simple behavior in the soil-dwelling nematode, C. elegans. A tap administered to the side of a petri plate acts as a nonlocalized mechanical stimulus to the worms within. Most adult worms respond to this tap stimulus with backward locomotion, an action known as the tap-withdrawal response. This behavior has been thoroughly characterized and the neural circuit mediating it has been determined. The response habituates following repeated stimulation, and current work is aimed at elucidating the mechanism behind this simple form of nonassociative learning. Changes in cell excitability and the strength of glutamatergic synapses play key roles in mediating this plasticity. [ABSTRACT FROM AUTHOR]

Long-term memory for habituation to tap in Caenorhabditis elegans depends on glr-1, a homolog of mammalian non-NMDA glutamate receptors; mutations in glr-1 blocked long-term memory formation. Green fluorescent protein (GFP) constructs were used to visualize glr-1 expression in the interneurons of the mechanosensory circuit and synaptobrevin in the tap sensory neurons of trained and untrained worms. Trained animals had less GLR-1::GFP expression than untrained animals; there was no difference in the vesicle marker synaptobrevin. Heat shock during training blocked both the behavioral expression of long-term memory and the change in GLR-1::GFP expression. Thus, long-term memory in C. elegans is dependent on glr-1 and likely involves changes in the expression or localization of glutamate receptors. [ABSTRACT FROM AUTHOR]

Presents a study on whether context conditioning plays a role in habituation caernorhabditis elegans and whether context mediates its effects by means of a context-unconditional stimulus association. Information on related studies; Experimental methods; Results and discussions.

Habituation and spontaneous recovery from habituation to tap were studied across development in C. elegans. Unlike adult worms, larval worms do not consistently swim backwards to tap, but reverse half of the time and accelerate forward half of the time. In adult worms, the tap response is produced by the integration of two competing circuits: The head touch circuit, mediated by ALM and AVM sensory neurons, produces backward movement (reversals); the tail touch circuit, mediated by PLM neurons, produces forward movement (accelerations). Because the response type changes over development, habituation of each of the subcircuits was studied separately. Habituation of the head touch circuit was studied by laser ablating PLM, and habituation of the tail circuit was studied by ablating ALM. Worms were tested at six stages of development at either 10- or 60-s interstimulus intervals. All stages of development showed normal habituation and spontaneous recovery at both interstimulus intervals. © 2000 John Wiley & Sons, Inc. Dev Psychobiol 36: 261–270, 2000 [ABSTRACT FROM AUTHOR]

Assesses the habituation of the tap withdrawal reflex of Caenorhabditis elegans to determine whether the kinetics of recovery from habituation were dependent on the interstimulus interval (ISI) used during habituation training or on the rate and asymptotic level of habituation produced at a given ISI. Use of laser ablation to alter habituation kinetics.

The article focuses on the importance of habituation mechanism in cognitive function. Topics include an overview of the habituation concept, the behavioral and animal models used in the habituation mechanism study, and the role played by molecular and synaptic processes in behavioral habituation. Also discussed are the influence of brain's modulatory norepinephrine system in odor memory and habituation in rats, the putative role of habituation as a cortical dysfunction marker.

Abnormalities in the simplest form of learning, habituation, have been reported in a variety of neuropsychiatric disorders as etiologically diverse as Autism Spectrum Disorder, Fragile X syndrome, Schizophrenia, Parkinson’s Disease, Huntington’s Disease, Attention Deficit Hyperactivity Disorder, Tourette’s Syndrome, and Migraine. Here we provide the first comprehensive review of what is known about alterations in this form of non-associative learning in each disorder. Across several disorders, abnormal habituation is predictive of symptom severity, highlighting the clinical significance of habituation and its importance to normal cognitive function. Abnormal habituation is discussed within the greater framework of learning theory and how it may relate to disease phenotype either as a cause, symptom, or therapy. Important considerations for the design and interpretation of habituation experiments are outlined with the hope that these will aid both clinicians and basic researchers investigating how this simple form of learning is altered in disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: The ability to learn and remember is critical for all animals to survive in the ever-changing environment. As we age, many of our biological faculties decay and of these, decline in learning and memory can be the most distressing. To carefully define age-dependent changes in learning during reproductive age in the nematode Caenorhabditis elegans, we performed a parametric behavioral study of habituation to nonlocalized mechanical stimuli (petri plate taps) over a range of intensities in middle-aged worms. We found that as worms age (from the onset of reproduction to the end of egg laying), response probability habituation increases (at both 10- and 60-second interstimulus intervals) and that these age-related changes were associated with a decrease in the discrimination between stimuli of different intensities. We also used optogenetics to investigate where these age-dependent changes occur. Our data suggest that the changes occur upstream of mechanosensory neuron depolarization. These data support the idea that declines in stimulus intensity discrimination abilities during aging may be one variable underlying age-related cognitive deficits. [Copyright &y& Elsevier]