Impairment of novelty-dependent hippocampal behavioural tagging in Septin5-deficient mice

Septin-5 is a GTP-binding protein implicated in synaptic vesicle exocytosis and 22q11.2 deletion-related neuropsychiatric disorders. We recently showed that Septin5-deficient (Septin5^-/-) mice display intact hippocampal spine ultrastructure, but marked deficits in both recent and remote contextual fear memory, whereas cued fear memory is preserved. Building on these findings, we asked whether Septin-5 is required for baseline forms of hippocampus-dependent spatial and object recognition memories, or more selectively for novelty-dependent memory stabilization. Using congenic Septin5^-/- mice, we performed a behavioural test battery including hippocampus-dependent spatial and object recognition tasks. Septin5^-/- mice showed normal performance in T-maze (spontaneous and forced alternation), Barnes maze (acquisition and recent/remote spatial reference memory), and object location memory. After 5-min training in the novel object recognition task, short-term recognition memory was indistinguishable between genotypes. Together with our previous report that long-term object recognition after 15-min training is intact in Septin5^-/- mice, these results indicate that Septin-5 is dispensable for a broad set of hippocampus-dependent spatial and object recognition memories despite contextual fear deficits. In contrast, Septin5^-/- mice exhibited a selective deficit in behavioural tagging: in wild-type mice, novelty exploration 30 min after 5-min object training converted an otherwise labile trace into a 24-h memory, whereas this novelty-induced stabilization was absent in Septin5^-/- mice. Thus, Septin-5 is not required for baseline performance in hippocampus-dependent spatial and object recognition tasks, but is implicated in novelty-dependent stabilization of weak hippocampal memories under the established 10-min novelty exposure condition, consistent with a contribution to synaptic tagging-like processes.