Regulation of Response Properties and Operating Range of the AFD Thermosensory Neurons by cGMP Signaling

Abstract

SUMMARY Background The neuronal mechanisms that encode specific stimulus features in order to elicit defined behavioral responses are poorly understood. C. elegans forms a memory of its cultivation temperature (Tc) and exhibits distinct behaviors in different temperature ranges relative to Tc. In particular, C. elegans tracks isotherms only in a narrow temperature band near Tc. Tc memory is in part encoded by the threshold of responsiveness (T*AFD) of the AFD thermosensory neuron pair to temperature stimuli. However, since AFD thermosensory responses appear to be similar at all examined temperatures above T*AFD, the mechanisms that generate specific behaviors in defined temperature ranges remain to be determined. Results Here, we show that the AFD neurons respond to the sinusoidal variations in thermal stimuli followed by animals during isothermal tracking (IT) behavior only in a narrow temperature range near Tc. We find that mutations in the AFD-expressed gcy-8 receptor guanylyl cyclase (rGC) gene result in defects in the execution of IT behavior, and are associated with defects in the responses of the AFD neurons to oscillating thermal stimuli. In contrast, mutations in the gcy-18 or gcy-23 rGCs alter the temperature range in which IT behavior is exhibited. Alteration of intracellular cGMP levels via rGC mutations or addition of cGMP analogs shift the lower and upper ranges of the temperature range of IT behavior in part via alteration in T*AFD. Conclusions Our observations provide insights into the mechanisms by which a single sensory neuron type encodes features of a given stimulus to generate different behaviors in defined zones.

GCY-8, PDE-2, and NCS-1 are critical elements of the cGMP-dependent thermotransduction cascade in the AFD neurons responsible for C. elegans thermotaxis

“…Consistent with prior work showing that most gcy-8 mutant AFD neurons fail to generate calcium signals in response to thermal fluctuations (Wasserman et al, 2011), the present experiments show that GCY-8 is critical for the generation of full amplitude ThRCs in AFD neurons studied (Fig. 2).…”

“…S1). Collectively and consistent with prior work (Inada et al, 2006;Wasserman et al, 2011), these the sensory ending (Inada et al, 2006), a process that could include temperature-dependent regulation of both the synthesis and hydrolysis of cGMP. PDEs are conserved enzymes that convert cyclic nucleotides to their monophosphate cognates and are inhibited nonspeci fically by 3-isobutyl-1-methylxanthine (IBMX).…”

“…If such manipulations increase intracellular cGMP as expected, treating wild-type animals with a nonhydrolyzable analogue of cGMP such as 8-Br-cGMP should also increase T *. Although we could not detect any effect of including 8-Br-cGMP in the recording pipette on the generation of ThRCs (not depicted), exogenous 8-bromo-cGMP does increase T * for warming-evoked calcium transients (Wasserman et al, 2011). But we note that even in wild-type AFD neurons, the value for T * is not fixed.…”

“…From the present experiments, we draw two main conclusions about AFD thermotransduction: PDE activity helps to set both the threshold, T *, and the lifetime of ThRCs, and, of two PDE genes expressed in AFD, only PDE-2 is required for responses to temperature. Because work extending over the past decade has shown that AFD function depends on a signaling network that includes guanylate cyclases and a cGMP-gated ion channel (Kimura et al, 2004;Clark et al, 2006;Ramot et al, 2008a;Wasserman et al, holding temperatures (Fig. 6 C).…”

“…1, B and C). The simplest interpretation of these findings is that other neurons which play a critical role in isothermal tracking Wasserman et al, 2011) and migration in linear thermal gradients (Glauser et al, 2011). Animals with defects in all three genes fail to respond to thermal gradients (Inada et al, 2006;Beverly et al, 2011) and lack detectable ThRCs (Ramot et al, 2008a).…”