Neurobiology Secreted Protein Linked to Learning

To get a handle on how neuronal circuits manage integration of multiple signals, Ishihara et al. turned to Caenorhabditis elegans. The worm provides a system amenable to genetic analysis with a relatively simple nervous system of only a few hundred neurons. Wild-type animals are attracted to the odorant diacetyl and repulsed by Cu2⁺. Normally, avoidance of Cu2⁺ can be suppressed by the presence of diacetyl. But in hen-1 mutants, diacetyl was less effective in luring the animals across a barrier of Cu2⁺. This appeared not to be a result of insensitivity to diacetyl, because in the absence of Cu2⁺, the hen-1 mutants were just as sensitive to attractant properties of diacetyl. Furthermore, the hen-1 mutants were less sensitve than wild-type animals to Cu2⁺ as an inhibitor of chemotaxis toward diacetyl. Thus, the defect seems to lie in the interaction or integration of the two signals. Wild-type worms are attracted toward a source of NaCl, but can be conditioned to avoid the salt if they are starved in the presence of NaCl. In this behavioral assay, the hen-1 mutants were again less sensitive to interacting signals and showed a smaller change in behavior after conditioning. The HEN-1 protein appears to be a secreted protein with a region of similarity to the low density lipoprotein receptor. Although HEN-1 is normally expressed only in two pairs of neurons, normal behavior of hen-1 mutants was restored even if the protein was expressed only in neurons that usually do not make the protein. Discovering just how HEN-1 influences neuronal function may provide insights into mechanisms by which neuronal circuits process sensory information to affect behavior.

T. Ishihara, Y. Iino, A. Mohri, I. Mori, K. Gengyo-Ando, S. Mitani, I. Katsura, HEN-1, a secretory protein with an LDL receptor motif, regulates sensory integration and learning in Caenorhabditis elegans. Cell 109, 639-649 (2002). [Online Journal]