Title:

Neuronal Primary Cilia Regulate Hippocampal Neuronal Priming and Trace Memory Formation

Memory is thought to be encoded by sparsely distributed neuronal ensembles in memory-related regions. Using in vivo calcium imaging, we have previously discovered that a small fraction of “primed neurons” in the hippocampus actively engage in trace memory information by forming burst synchronization. Our imaging system allows for direct visualization of neuronal activity in freely behaving animals. However, its application is limited by some motion artefacts and low signal-to-noise ratio (SNR). We have developed a robust computational algorithms to eliminate artificial burst, numerically define primed neurons, and compute memory-associated neuronal synchronization. Primary cilia are microtubule-based sensory organelles present in most vertebrate cells including neurons. The deflection of neuronal cilia is associated with numerous neurological disorders like intellectual disability, cognitive impairment, and neurodegeneration. It is unclear that how neuronal primary cilia regulate the activity of hippocampal neurons and affect hippocampus-dependent memory formation. We utilized two loss-of-function mouse models a) globally ablated primary cilia in adult mice (IFT88 global KO) and b) shortened primary cilia in the adult forebrain (Arl13b global KO). We subjected these mice to trace fear conditioning tests in conjunction with in vivo calcium imaging study. Here we show that both of KOs display a markedly impaired learning ability than their littermate Controls. The overall activity level of hippocampal neurons of KOs is significantly decreased compared to Controls. Moreover, the burst synchronization following fear conditioning is drastically suppressed. These data suggest that neuronal primary cilia regulate hippocampal neuronal priming.

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