Loss of CaMKI Function Disrupts Salt Aversive Learning in C. elegans

Abstract

The ability to adapt behavior to environmental fluctuations is critical for survival of organisms ranging from invertebrates to mammals. can learn to avoid sodium chloride when it is paired with starvation. This behavior may help animals avoid areas without food. Although some genes have been implicated in this salt-aversive learning behavior, critical genetic components, and the neural circuit in which they act, remain elusive. Here, we show that the sole worm ortholog of mammalian CaMKI/IV, CMK-1, is essential for salt-aversive learning behavior in hermaphrodites. We find that CMK-1 acts in the primary salt-sensing ASE neurons to regulate this behavior. By characterizing the intracellular calcium dynamics in ASE neurons using microfluidics, we find that loss of has subtle effects on sensory-evoked calcium responses in ASE axons and their modulation by salt conditioning. Our study implicates the expression of the conserved CaMKI/CMK-1 in chemosensory neurons as a regulator of behavioral plasticity to environmental salt in Like other animals, the nematode depends on salt for survival and navigates toward high concentrations of this essential mineral. In addition to its role as an essential nutrient, salt also causes osmotic stress at high concentrations. A growing body of evidence indicates that balances the requirement for salt with the danger it presents through a process called salt-aversive learning. We show that this behavior depends on expression of a calcium/calmodulin-dependent kinase, CMK-1, in the ASE salt-sensing neurons. Our study identifies CMK-1 and salt-sensitive chemosensory neurons as key factors in this form of behavioral plasticity.

A system for the high-throughput analysis of acute thermal avoidance and adaptation in C. elegans

“…Although future work using the INFERNO and ThermINATOR systems will allow detailed investigations on these questions, we already started to characterize the molecular pathways underpinning this plasticity and tested the impact of mutations in genes encoding proteins working in the CKK-1/CMK-1/ CRH-1 pathway. This pathway was chosen because we and others had previously demonstrated its implication in the plasticity induced by long-lasting thermal changes [28,29], in the salt learning process [30] and in response to repeated acute mechanical stimulations [31]. Our data confirm that CMK-1 can act to increase thermal sensitivity.…”

“…This plasticity involves the Ca 2+ signaling within thermosensory neurons and notably requires the Ca 2+ /calmodulin-dependent protein kinase-1 (CMK-1) and its upstream regulatory kinase Ca 2+ /calmodulin-dependent protein kinase kinase-1 (CKK-1) [27,28]. This pathway is also implicated in the response adaptation to other types of stimuli, such as adaptation in the innocuous range of temperature [29], salt learning [30], and habituation to repeated acute mechanical stimuli [31]. Nothing is known on whether animals would adapt in response to long-term, repeated noxious heat stimulations.…”

Insights into the roles of CMK-1 and OGT-1 in interstimulus interval-dependent habituation inCaenorhabditis elegans

“…The C. elegans genome encodes a single homologue of CaMK1/4, CMK-1 [17]. Strains with mutations in cmk-1 are superficially wild-type [18]; however, a recent series of studies have implicated CMK-1 in several forms of behavioural plasticity, including experience-dependent thermotaxis and heat avoidance [19][20][21][22][23].…”

Characterization of TMC-1 in C. elegans sodium chemotaxis and sodium conditioned aversion

“…G-protein signaling, serotonin, and glutamate have all been implicated in gustatory plasticity [20,21]. A related phenomenon called salt chemotaxis learning has been shown to be dependent on insulin signaling and the calcium/calmodulin-dependent kinase, CMK-1 [22][23][24][25]. Here nematodes will avoid sodium following a period of starvation in the presence of NaCl.…”