Type 3 adenylyl cyclase in the MOE is involved in learning and memory in mice

Abstract

Although olfactory dysfunction is related to learning and memory impairment, the causal relationship between main olfactory epithelium (MOE) disruption and learning and memory is still unknown. The present study aimed to establish whether MOE disruption causes learning and memory impairment and whether the expression of type 3 adenylyl cyclas (AC₃) in the MOE is related to learning and memory. First, the buried food test was carried out to confirm that MOE function was disrupted in mice treated with nasal instillation of zinc sulfate (ZnSO₄ mice), and mice with specific knockdown of AC₃ in the MOE by CRISPR/Cas9 technology (AC_3KD/MOE mice). Then, behavioural tasks associated with learning and memory were administered. ZnSO₄ mice and AC_3KD/MOE mice showed impairments in learning and memory tests, including the novel object recognition test, the step-down passive avoidance test, the Morris water maze test, and the Y-maze test. Our data demonstrate that MOE disruption caused by nasal exposure to ZnSO₄ or specific knockdown of AC₃ in the MOE resulted in learning and memory impairment, and they further demonstrate that the expression of AC₃ in the MOE plays a major role in learning and memory.

Keywords: Anosmia; Learning and memory; Main olfactory epithelium; Olfactory dysfunction; Type 3 adenylyl cyclase.