PT - JOURNAL ARTICLE AU - Takehisa Suzuki AU - Ryota Nakahigashi AU - Masaatsu Adachi AU - Toshio Nishikawa AU - Hideki Abe TI - Green spotted puffers can detect an almost nontoxic TTX analog odor using crypt olfactory sensory neurons AID - 10.1101/2021.09.16.460554 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.09.16.460554 4099 - http://biorxiv.org/content/early/2021/09/28/2021.09.16.460554.short 4100 - http://biorxiv.org/content/early/2021/09/28/2021.09.16.460554.full AB - Tetrodotoxin (TTX) is a well-known neurotoxin that functions as a defense substance for toxic puffers. Several behavioral studies reported that TTX attracts toxic puffers belonging to the genus Takifugu. Although our electrophysiological and behavioral studies showed that a TTX analog, 5,6,11-trideoxyTTX, acts as an olfactory chemoattractant for grass puffers (T. alboplumbeus), it is unclear whether toxic puffers are commonly attracted to 5,6,11-trideoxyTTX, and which types of olfactory sensory neurons (OSNs) detect 5,6,11-trideoxyTTX.Here we investigated whether the green spotted puffer (Dichotomyctere nigroviridis), a phylogenetically different species from the grass puffer, is attracted to 5,6,11-trideoxyTTX. Administration of 5,6,11-trideoxyTTX attracted green spotted puffers, but TTX or vehicle did not. Furthermore, immunohistochemistry of the olfactory epithelium exposed to 5,6,11-trideoxyTTX with an antibody against phosphorylated ribosomal protein S6 (pS6), a neuronal activity marker, labeled oval cells with apical invagination. These oval cells were also labeled by the antibody against S100, a specific marker of crypt OSNs. Thus, our results suggest that 5,6,11-trideoxyTTX acts as an olfactory chemoattractant that is detected by crypt-type OSNs in the olfactory epithelium of green spotted puffers. Toxic puffers may use 5,6,11-trideoxyTTX as an olfactory chemoattractant involved in reproduction and parental care or as an olfactory cue of TTX-bearing organisms for effective toxification.Summary statement Behavioral and immunohistochemical experiments suggest that an almost nontoxic TTX analog, 5,6,11-trideoxyTTX, acts as an olfactory chemoattractant for green spotted puffers, and crypt-type olfactory sensory neurons detect it.Competing Interest StatementThe authors have declared no competing interest.