The nematode C. elegans establishes a long-term thermal memory by associating temperature with the presence of food. Thermotactic behavior is sensitive to both chemical and thermal cues. The integration of multiple sensory inputs in the formation of long-term memory and thermotactic decision-making occur in a strikingly compact neural circuit. We will present recent results shedding light on the previously unknown molecular details of long-term thermal memory. One can measure thermal memory by cultivating worms at a given temperature (Tc) and subsequently placing them on a temperature gradient in the absence of food. Under such conditions the worms track isotherms near Tc. When worms which were cultivated at Tc=15C are incubated for increasing intervals of time at T=25C prior to being placed on the gradient their tracks gradually shift until they fully adapt to T=25C. Similarly, worms shifted from high to low temperatures gradually track lower temperatures over time. Combining novel biophysical assays with a reverse genetic approach we have identified genes, mutations in which result in defects in thermal adaptation and isothermal tracking abilities. The diacylglycerol kinase gene
dgk-3 was identified as being expressed strongly in AFD neurons and more weakly in other sensory neurons. We found that when shifted from Tc=15C to T=25C
dgk-3 mutants are about 3-fold slower than wild type in learning the higher temperature, although when shifted from Tc=25 to T=15 they learn at the wild-type rate. Moreover, the isothermal tracks made by them are shorter than wild type tracks. Expressing
dgk-3 in AFD neurons in a
dgk-3 mutant background rescues the wild type behavior.
dgk-3 mutants are predicted to be defective in the conversion of DAG to phosphatidic acid, resulting in a buildup of higher levels of DAG and likely its downstream metabolites the polyunsaturated fatty acids (PUFAs). We examined if fatty acids play a role in long-term thermal memory. Interestingly,
fat-4 mutants, which were shown to have an excess of omega-3 arachidonic acid (O3AA) and lack arachinoic acid (AA) and eicosapentaneoic acid (EPA), display a slow learning rate reminiscent of
dgk-3 mutants in temperature upshift assays. In addition,
fat-1;
fat-4 double mutants, which were shown to have an excess of dihomo--linolenic acid (DGLA) and lack O3AA, AA and EPA, display short isothermal tracks but learn at the wild-type rate. Intriguingly, PUFAs have been shown to gate TRP channels which have been implicated in thermosensation in vertebrates and in photo detection in Drosophila. Ongoing experiments are aimed at further analyses of the roles of various signaling molecules in the formation, storage and retrieval of thermal memory.