Caenorhabditis elegans habituate to mechanosensory stimuli in the form of mechanical taps to the side of the Petri dish in which they live. When a distributed training protocol of 4 blocks (each separated by an hour) of 20 taps (with a 60 s interstimulus interval) is used, C. elegans show long-term memory for this habituation [1]. Recently, dopamine receptors have been found to be expressed on the mechanosensory neurons involved in this tap withdrawal response and mutations in a couple of genes important for dopamine neurotransmission have been reported to cause faster short-term habituation of reversal frequency in response to tap [2]. Therefore, we tested short- and long-term habituation to tap in three dopamine transmission mutants:
dop-1(
ev748), which lacks the D1-like dopamine receptor usually expressed in the mechanosensory neurons (received from Van Tol);
cat-2(
e1112), which lacks the ability to synthesize dopamine (received for CGC); and
dat-1(
ok157), which lacks the dopamine transporter (received from Rand and Duerr). Both the
dop-1 and
cat-2 mutants, which have decreased dopamine neurotransmission, had relatively normal habituation of reversal magnitude. The
dat-1 mutants, with an excess of dopamine neurotransmission, showed slightly, but significantly, slower habituation than wild-type worms. Interestingly, all three mutants had a long-term memory deficit, suggesting that both decreased or excessive dopamine neurotransmission disrupts long-term memory. The mechanosensory neurons are glutamatergic and this long-term memory depends on
glr-1, a glutamate receptor subunit, and is correlated with a down-regulation of
glr-1 expression [3]. It appears as though dopamine is modulating the excitability of these glutamate neurons, which has been shown to occur between dopamine and glutamate neurons in other organisms [4]. This suggests only a critical amount of excitability paired with distributed training allows for the formation of long-term memory. Currently, we are attempting to rescue these memory deficits using both genetic and pharmacological techniques. Funded by NSERC and MSFHR to ACG and NSERC to CHR.