Calcium-calmodulin protein kinase II (CaMKII) is widely expressed throughout the mammalian brain and has long been known to play a role in learning and memory. In C. elegans, the
unc-43 gene is an ortholog to mammalian CaMKII and although the role of UNC-43 has been well-characterized in basic worm function (e.g., egg-laying, defecation, etc.), studies investigating the role of UNC-43 in C. elegans learning has been limited due to the uncoordinated motor phenotype
unc-43 mutant strains exhibit. The current study utilized the
unc-43(
gk452) mutant strain (generated and identified by the C. elegans Knockout Consortium) as this strain is superficially wild-type displaying no obvious motor defects thus allowing for its use in behavioral paradigms. Associative learning was tested by employing both an associative chemotaxis assay and an associative chemoavoidance test. Both tests consisted of exposing worms to an attractant compound (i.e., NaCl) under "no food" conditions and then testing for either attraction to or avoidance of NaCl. Results from both associative protocols reveal that unlike wild-type,
unc-43(
gk452) worms continue to show a preference for NaCl after a one-hour "no food" pairing. To determine if this learning phenotype is specific for associative conditioning,
unc-43(
gk452) worms underwent habituation training (non-associative conditioning) that included repeated exposure to a low-intensity mechanosensory stimulus; locomotor reversal responses were scored. When habituation stimuli are delivered at a 60 second interstimulus interval,
unc-43(
gk452) worms show a slower rate of response decrement compared to wild-type, suggesting habituation is somewhat impeded, although not altogether absent. Taken together, it is concluded that the
unc-43(
gk452) strain displays an impairment in associative learning and possibly plays a role in non-associative conditioning as well. The
unc-43(
gk452) mutant strain consists of an insertion/deletion modification that includes the deletion of coding exon 5 of the UNC-43C isoform. Future work will assess if more specific mutations within this region account for this learning phenotype. Support for this project provided by BRAIN funding in the form of new faculty start-up and stipend to JKR..