Activity Hierarchy Measurement to Establish Trace Memory-eligible “Primed” Neurons

Abstract

AbstractEpisodic memory is thought to be preferentially encoded by sparsely distributed memory-eligible “primed” neurons in memory-related regions. Based onin vivocalcium imaging on freely behaving mice, we developed an analytical method to determine neuronal activity hierarchy and establish hippocampal primed neurons. Neurons with high activity and memory-associated burst synchronization are identified as primed neurons. When a trace fear memory is being formed or retrieved, the major pattern of the calcium dynamics is predominantly mediated by primed neurons and highly correlated with mouse freezing behaviors. In cilia knockout mice that exhibit severe learning deficits, the percentage of their primed neurons is drastically reduced, and any burst synchronization is strongly suppressed. Consistently, the first principal pattern of cilia knockout neurons does not fully distinguish itself from other minor components or correlate with mouse freezing behaviors. To reveal how a portion of neurons get primed, we developed a numerical model of a simplified neural network that incorporates simulations of linear and non-linear weighted postsynaptic conductance, modeling AMPAR- and NMDAR-mediated conductances respectively. Moderate non-linear to linear conductance ratios can naturally lead to the emergence of primed neurons. In such cases, the neuronal firing averages show a right-skewed log-distribution, similar to the distributions of hippocampal c-Fos expression and the activity levels measured by calcium imaging. Together, this study reveals a novel method to determine neuronal activity hierarchy. Our simulation suggests that the accumulation of biased synaptic transmission mediated by the non-linear synaptic component represents an important mechanism for neuronal priming.