Habituation as an adaptive shift in response strategy mediated by neuropeptides

Abstract

Habituation is a non-associative form of learning characterized by a decremented response to repeated stimulation. It is typically framed as a process of selective attention, allowing animals to ignore irrelevant stimuli in order to free up limited cognitive resources. However, habituation can also occur to threatening and toxic stimuli, suggesting that habituation may serve other functions. Here we took advantage of a high-throughput Caenorhabditis elegans learning assay to investigate habituation to noxious stimuli. Using real-time computer vision software for automated behavioral tracking and optogenetics for controlled activation of a polymodal nociceptor, ASH, we found that neuropeptides mediated habituation and performed an RNAi screen to identify candidate receptors. Through subsequent mutant analysis and cell-type-specific gene expression, we found that pigmentdispersing factor (PDF) neuropeptides function redundantly to promote habituation via PDFR-1-mediated cAMP signaling in both neurons and muscles. Behavioral analysis during learning acquisition suggests that response habituation and sensitization of locomotion are parts of a shifting behavioral strategy orchestrated by pigment dispersing factor signaling to promote dispersal away from repeated aversive stimuli.

Habituation Is More Than Learning to Ignore: Multiple Mechanisms Serve to Facilitate Shifts in Behavioral Strategy

“…This dispersal response is mediated by PDF neuropeptide signaling and is not observed in PDFR‐1 mutants. Adapted with permission . Copyright 2017, Nature Research.…”

“…In this view, once animals learn to stop responding to the training stimuli, they will revert to their prestimulation behavior. However, these studies show that in reality, animals begin to alter other behaviors before they are fully habituated to the repeated training stimulus to seamlessly shift behavioral strategy . Thus, habituation may not be a passive learning process after all; animals may play a much more active role in this form of learning to optimize their behavioral strategy to adapt to a particular physiological state and environmental context.…”

“…However, these studies show that in reality, animals begin to alter other behaviors before they are fully habituated to the repeated training stimulus to seamlessly shift behavioral strategy. [48] Thus, habituation may not be a passive learning process after all; animals may play a much more active role in this form of learning to optimize their behavioral strategy to adapt to a particular physiological state and environmental context. If this hypothesis is correct, then one should always be able to find 1) a concurrent change in other ongoing behaviors during habituation training and 2) an increase in activity in some other part of the nervous system in addition to the decrementing areas mediating habituation.…”

High‐Throughput Analysis of Behavior Under the Control of Optogenetics in Caenorhabditis elegans

“…It is critical to adjust the data analysis parameters used to define a "stimulus-evoked response" in Choreography accordingly. For example, a 2-sec blue-light stimulus that activates ChR2 in ASH triggers a response of a longer latency than the response when the same blue-light stimulus activates ChR2 in the mechanosensory neurons (Ardiel et al, 2016(Ardiel et al, , 2017.…”

“…Here, we describe a detailed basic protocol that uses our high‐throughput behavioral tracking system, the Multi‐Worm Tracker (freely available at https://sourceforge.net/projects/mwt/), in conjunction with a low‐cost and effective custom‐built light‐emitting diode (LED) light source (Support Protocol 1) and a cofactor solution (Support Protocol 2) to study the behavior of populations of freely behaving C. elegans under the control of optogenetics (Ardiel et al., , ). This method is versatile and is easy to adapt to other worm‐tracking systems.…”