Research Interests

Neural basis of thermotactic behavior in Caenorhabditis elegans
All of an animals behavior, the choices that it makes and how it reacts to sensations or experiences, is encoded in the structure and function of its neural system. A general goal of neurobiology is to understand how neural systems encode behavior. We pursue this goal by studying the nematode worm Caenorhabditis elegans because it offers several advantages over other model organisms including 1) simple, robust, and quantifiable behaviors, 2) a relatively small and invariant neural system of 302 neurons, and 3) powerful methods for manipulating the worms genetic makeup.

We focus on the worm’s thermotactic behavior. Worms associate the presence of food with the ambient temperature; when cultivated at a particular temperature, worms learn that temperature. If food is removed, worms attempt to relocate food by searching near the remembered temperature of their cultivation. This thermotactic search has two phases. First, worms migrate towards the remembered temperature. Second, upon arriving near the remembered temperature, worms prefer to crawl along isotherms. By tracking isotherms, worms are able to navigate near the remembered temperature for an extended duration without straying.

We strive to understand how temperature sensing and signaling among neurons within the brain of the worm results in thermotactic behavior and decision-making. We burn the candle at both ends, working at both the behavioral and neuronal level. For instance, in one recent study, we identified patterns in worm behavior by quantifying thermotactic responses to defined thermal stimuli (Ryu & Samuel, 2002). In another recent study we found a matching pattern in neuronal activity that might give rise to one of these behavioral patterns (Samuel et al., 2003). At present, we have more behavioral patterns than we can account for at the neuronal level. This is because measuring neuronal activity in C. elegans is unusually difficult. The worm poses unique challenges to the use of conventional methods.

We have developed a new assay for measuring neuronal activity in the worm using pH-sensitive GFP to monitor the rates of synaptic transmission in the intact worm. But we are continuing to develop new and more powerful methods. At present we are using another variant of GFP (called G-CaMP) that is sensitive to the rises in intracellular calcium concentration that accompany neuronal activity. We are also using laser microscopy not only to measure neuronal activity, but in a novel form of laser surgery. In collaboration with Prof. Eric Mazur (Dept. Physics, Harvard), we have found that focused femtosecond pulses of infrared light can cut neuronal fibers in C. elegans without killing the neuron itself. By studying the behavior of such surgically modified worms, we can determine the information that is normally carried by the fiber.

Selected Publications:

Samuel, A.D., Silva, R.A., Murthy, V.N. (2003). "Synaptic activity of the AFD neuron in Caenorhabditis elegans correlates with thermotactic memory. J Neurosci. Jan 15;23(2):373-6.

Ryu, W.S., Samuel, A.D. (2002). "Thermotaxis in Caenorhabditis elegans analyzed by measuring responses to defined thermal stimuli". J Neurosci. Jul 1;22(13):5727-33.

Samuel, A.D., Murthy, V.N., Hengartner, M.O. (2001). "Calcium dynamics during fertilization in C. elegans". BMC Dev Biol. 1(1):8.