Takeishi A (2022) Curr Opin Neurobiol "Environmental-temperature and internal-state dependent thermotaxis plasticity of nematodes."

Takeishi A

[Curr Opin Neurobiol, 2022]

Thermotaxis behavior of Caenorhabditis elegans is robust and highly plastic. A pair of sensory neurons, AFD, memorize environmental/cultivation temperature and communicate with a downstream neural circuit to adjust the temperature preference of the animal. This results in a behavioral bias where worms will move toward their cultivation temperature on a thermal gradient. Thermotaxis of C.elegans is also affected by the internal state and is temporarily abolished when worms are starved. Here I will discuss how C.elegans is able to modulate its behavior based on temperature by integrating environmental and internal information. Recent studies show that some parasitic nematodes have a similar thermosensory mechanism to C.elegans and exhibit cultivation-temperature-dependent thermotaxis. I will also discuss the common neural mechanisms that regulate thermosensation and thermotaxis in C.elegans and Strongyloides stercoralis.

Takeishi A et al. (2016) Neuron "Receptor-type Guanylyl Cyclases Confer Thermosensory Responses in C.elegans."

Takeishi A, Hapiak VM, Sengupta P, O'Leary T, Yu YV, Bell HW

[Neuron, 2016]

Thermosensation is critical for optimal regulation of physiology and behavior. C.elegans acclimates to its cultivation temperature (Tc) and exhibits thermosensitive behaviors at temperatures relative to Tc. These behaviors are mediated primarily by the AFD sensory neurons, which are extraordinarily thermosensitive and respond to thermal fluctuations at temperatures above a Tc-determined threshold. Although cGMP signaling is necessary for thermotransduction, the thermosensors in AFD are unknown. We show that AFD-specific receptor guanylyl cyclases (rGCs) are instructive for thermosensation. In addition to being necessary for thermotransduction, ectopic expression of these rGCs confers highly temperature-dependent responses onto diverse celltypes. We find that the temperature response threshold is determined by the rGC and cellular context, and that multiple domains contribute to their thermosensory properties. Identification of thermosensory rGCs in C.elegans provides insight into mechanisms of thermosensation and thermal acclimation and suggests that rGCs may represent a new family of molecular thermosensors.

Takeishi A et al. (2020) Elife "Feeding state functionally reconfigures a sensory circuit to drive thermosensory behavioral plasticity."

Sengupta P, Takeishi A, Harris N, Yeon J, Yang W

[Elife, 2020]

Internal state alters sensory behaviors to optimize survival strategies. The neuronal mechanisms underlying hunger-dependent behavioral plasticity are not fully characterized. Here we show that feeding state alters <i>C. elegans</i> thermotaxis behavior by engaging a modulatory circuit whose activity gates the output of the core thermotaxis network. Feeding state does not alter the activity of the core thermotaxis circuit comprised of AFD thermosensory and AIY interneurons. Instead, prolonged food deprivation potentiates temperature responses in the AWC sensory neurons, which inhibit the postsynaptic AIA interneurons to override and disrupt AFD-driven thermotaxis behavior. Acute inhibition and activation of AWC and AIA, respectively, restores negative thermotaxis in starved animals. We find that state-dependent modulation of AWC-AIA temperature responses requires INS-1 insulin-like peptide signaling from the gut and DAF-16 FOXO function in AWC. Our results describe a mechanism by which functional reconfiguration of a sensory network via gut-brain signaling drives state-dependent behavioral flexibility.

Takeishi A et al. (2020) J Neurogenet "Temperature signaling underlying thermotaxis and cold tolerance in Caenorhabditis elegans."

Takagaki N, Takeishi A, Kuhara A

[J Neurogenet, 2020]

<i>Caenorhabditis elegans</i> has a simple nervous system of 302 neurons. It however senses environmental cues incredibly precisely and produces various behaviors by processing information in the neural circuit. In addition to classical genetic analysis, fluorescent proteins and calcium indicators enable <i>invivo</i> monitoring of protein dynamics and neural activity on either fixed or free-moving worms. These analyses have provided the detailed molecular mechanisms of neuronal and systemic signaling that regulate worm responses. Here, we focus on responses of <i>C. elegans</i> against temperature and review key findings that regulate thermotaxis and cold tolerance. Thermotaxis of <i>C. elegans</i> has been studied extensively for almost 50years, and cold tolerance is a relatively recent concept in <i>C. elegans</i>. Although both thermotaxis and cold tolerance require temperature sensation, the responsible neurons and molecular pathways are different, and <i>C. elegans</i> uses the proper mechanisms depending on its situation. We summarize the molecular mechanisms of the major thermosensory circuit as well as the modulatory strategy through neural and tissue communication that enables fine tuning of thermotaxis and cold tolerance.

Takeishi, Asuka et al. (2017) International Worm Meeting "Molecular and neuronal mechanisms underlying feeding state-dependent plasticity in thermotaxis behaviors."

Takeishi, Asuka, Sengupta, Piali

[International Worm Meeting, 2017]

Dynamic regulation of behaviors by past experience allows animals to exhibit responses that are most optimal for their reproduction and survival. Consequently, the same stimulus can elicit different behaviors in different individuals based on the individual's experience, internal state, and immediate context. The presence of food and feeding status are critical variables that modulate multiple behavioral strategies in C. elegans, including their navigation behaviors on spatial thermal gradients. While well-fed worms migrate to colder temperatures (negative thermotaxis) when they encounter temperatures higher than their cultivation temperature Tc, starvation for =30 min suppresses this behavior. Thus, feeding state-dependent regulation of thermosensory behaviors in C. elegans provides an attractive model system in which to study how internal state (starvation) is integrated with environmental cues (temperature) to alter neuronal circuit functions. Temperature-evoked responses in the AFD thermosensory neurons are largely unaffected upon starvation suggesting that the starvation signal is integrated elsewhere in the thermotaxis circuit to alter behavior. We find that the AWC and ASI sensory neurons play a role in mediating this starvation-dependent behavioral plasticity. Although ablation of ASI alone does not affect this plasticity, ablation of AWC alone, or AWC and ASI together, partially or fully abolish starvation-dependent suppression of negative thermotaxis, respectively. Interestingly, we observe that the subcellular localization of the CMK-1 CaMKI (calcium/calmodulin-dependent protein kinase I) enzyme we previously implicated in the feeding state-dependent dauer behavioral decision (Neal et al., 2015) is altered in AWC asymmetrically upon starvation. The INS-1 insulin pathway has previously been shown to contribute to starvation-dependent plasticity in thermotaxis behaviors (Kodama et al. 2006). We find that subcellular localization of CMK-1 is also altered in ins-1 mutants. Moreover, we find that basal activity of AWC is increased upon prolonged starvation, and in ins-1 and cmk-1 mutants. Taken together, we propose that feeding status is integrated into the thermotaxis circuit via regulation of AWC activity and potentially CMK-1-dependent gene expression changes to modulate thermotaxis behavior. Current experiments are aimed at examining the contribution of asymmetry in starvation-dependent changes in AWC function in mediating thermotaxis behavioral plasticity.

Takeishi*, Asuka et al. (2015) International Worm Meeting "AFD-specific receptor guanylyl cyclases can confer temperature responses onto diverse cell types."

Takeishi*, Asuka, Sengupta, Piali, Bell, Harold W., Hapiak, Vera M., Yu*, Yanxun V.

[International Worm Meeting, 2015]

C. elegans exhibits complex experience-dependent thermosensory behaviors on spatial thermal gradients. AFD has been identified as the major thermosensory neuron type, and AFD-ablated worms exhibit strong defects in thermotaxis behaviors. Measurements of temperature-evoked intracellular calcium dynamics and thermoreceptor current have shown that AFD responds to thermal variation at temperatures above a threshold temperature (T*) that is set by the animal's cultivation temperature (Tc). Thermotransduction in AFD is mediated by cGMP signaling, and requires the functions of the receptor guanylyl cyclases (rGCs), GCY-8, GCY-18 and GCY-23, the cGMP-dependent phosphodiesterase PDE-2, and the TAX-2 and TAX-4 cGMP-gated channels. However, the molecular mechanisms by which AFD senses temperature are still unknown.Previous studies have shown that many rGCs function as sensors for specific stimuli, suggesting that the AFD-expressed rGCs may themselves act as thermosensors. We found that misexpression of GCY-8, GCY-18 and GCY-23 in the non-thermosensory AWB and ASE chemosensory neurons is sufficient to confer warming-dependent changes in intracellular calcium (also see abstract by Yu, Takeishi et al). We further expressed each rGC singly or in combination in these neurons, and found that expression of GCY-23 alone confers temperature responses onto AWB and ASE in the physiological temperature range, whereas expression of GCY-18 confers responses to higher temperatures. Interestingly, in contrast to AFD, the T* of AWB and ASE misexpressing AFD-specific rGCs is not modulated by Tc, suggesting that the observed Tc -dependent plasticity in AFD thermosensory response threshold may be mediated by AFD-specific mechanisms. To ask whether misexpression in cell types lacking endogenous cGMP signaling pathways would also confer thermosensory responses, we next misexpressed the rGCs in vulval muscles. We found that vulval muscles misexpressing GCY-23 as well as TAX-2/TAX-4 also exhibit responses to temperature variation. Our results suggest that AFD-specific rGCs can confer thermosensory responses onto multiple neuronal and non-neuronal cell types, and raise the possibility that these proteins may be bona fide thermosensors in C. elegans.* - equal contributions.

Khan, M. et al. (2017) International Worm Meeting "The GCY-29 receptor guanylyl cyclase shapes thermosensory signaling in C. elegans."

Khan, M., Takeishi, A., Sengupta, P., Hapiak, V.

[International Worm Meeting, 2017]

The ability to sense and respond to external cues in the context of past experiences and current conditions is crucial for animals to survive and maintain functional homeostasis. Temperature represents a critical environmental variable that regulates nearly all physiological processes. Consequently, animals have evolved mechanisms to detect and respond to small changes in both external and internal temperature. Unlike many organisms that prefer a constant environmental temperature, the preferred temperature of C. elegans is governed by a 'memory' of its cultivation temperature (Tc). This temperature preference is plastic, and resets in an experience-dependent manner. These behaviors are mediated primarily by the AFD sensory neurons, which respond to temperature variations above a Tc-determined threshold. Thermotransduction in AFD is mediated by a subset of three receptor guanylyl cyclases (rGCs). We have recently shown that the AFD-expressed rGCs GCY-8, -18, and -23 are necessary and sufficient for thermosensation (Takeishi, Yu, et al., 2016). In addition to these rGCs, the AFD neurons also express the GCY-29 rGC. Similar to the thermosensory rGCs, GCY-29 is also localized to the AFD sensory endings. The goal of this work is to explore the role of GCY-29 in shaping AFD-mediated thermosensory signaling. Using calcium imaging and thermotaxis navigation behavioral analyses, we have found that GCY-29 contributes to the detection and tracking of temperature stimuli, as well as shaping the Tc-determined response threshold of AFD. Our findings suggest that GCY-29 may modulate the functions of the thermosensory rGCs to more precisely coordinate AFD response ranges and shape their thermosensory response profiles.

Yu*, Yanxun et al. (2015) International Worm Meeting "AFD-specific guanylate cyclases and CMK-1 mediate thermosensory signaling in AFD."

Yu*, Yanxun, Takeishi*, Asuka, Sengupta, Piali, Hapiak, Vera, Bell, Harrold

[International Worm Meeting, 2015]

Animals actively seek optimal temperatures for survival and reproduction. Unlike many organisms that exhibit a constant temperature preference, the preferred temperature of C. elegans is plastic, and set by their experience of their cultivation temperature. The AFD neurons are the primary thermosensory neurons in C. elegans, and drive thermosensory navigation behaviors on thermal gradients. Although the AFD neurons are known to respond to temperature variations of as little as 0.01 C, how worms sense temperature and set their temperature preference are still largely unknown. Thermosensation in AFD requires cGMP signaling, and molecules implicated in this pathway have been identified. These include receptor guanylyl cyclases (rGCs) expressed specifically in AFD, as well as phosphodiesterases, and cGMP-gated cation channels.To determine whether the AFD-specific rGCs GCY-8, GCY-18 and GCY-23 act as thermosensors, we misexpressed these rGCs singly or in combination in non-thermosensory neuron types, as well as in non-neuronal cells. We found that misexpression was sufficient to confer thermosensory responses onto both neuronal and non-neuronal cells (also see abstract by Takeishi & Yu et al). Each rGC appears to elicit temperature responses with different response thresholds. However, although the thermosensory response threshold in AFD adapts upon long-term exposure to a different temperature, the response threshold of rGC-misexpressing cells do not adapt similarly. Our work suggests that AFD-specific mechanisms including the function of the CMK-1 CaMKI enzyme may be important in regulating rGC gene expression and thermosensory adaptation in AFD. We are currently determining whether rGCs are sufficient to confer temperature responses upon heterologous expression, and identifying domains that may mediate thermosensation.* - equal contributions.

Neal SJ et al. (2015) Elife "Feeding state-dependent regulation of developmental plasticity via CaMKI and neuroendocrine signaling."

Hong M, Butcher RA, Takeishi A, O'Donnell MP, Neal SJ, Kim K, Park J, Sengupta P

[Elife, 2015]

Information about nutrient availability is assessed via largely unknown mechanisms to drive developmental decisions, including the choice of Caenorhabditis elegans larvae to enter into the reproductive cycle or the dauer stage. In this study, we show that CMK-1 CaMKI regulates the dauer decision as a function of feeding state. CMK-1 acts cell-autonomously in the ASI, and non cell-autonomously in the AWC, sensory neurons to regulate expression of the growth promoting daf-7 TGF- and daf-28 insulin-like peptide (ILP) genes, respectively. Feeding state regulates dynamic subcellular localization of CMK-1, and CMK-1-dependent expression of anti-dauer ILP genes, in AWC. A food-regulated balance between anti-dauer ILP signals from AWC and pro-dauer signals regulates neuroendocrine signaling and dauer entry; disruption of this balance in cmk-1 mutants drives inappropriate dauer formation under well-fed conditions. These results identify mechanisms by which nutrient information is integrated in a small neuronal network to modulate neuroendocrine signaling and developmental plasticity.

Neal SJ et al. (2015) Elife "Correction: Feeding state-dependent regulation of developmental plasticity via CaMKI and neuroendocrine signaling."

Neal SJ, Kim K, Hong M, Park J, Takeishi A, O'Donnell MP, Butcher RA, Sengupta P

[Elife, 2015]