KiF1a-regulated neuronal infrastructures in sensory and prefrontal cortices essential for fear memory and anxiety

Abstract Stress in social activities induces fears. Cellular infrastructures and molecular profiles underlying fear-relevant psychosis remain elusive. By giving psychological stress to mice that watched fear scenes in the resident/intruder paradigm, we have studied the features of neuronal infrastructures in visual, auditory and medial prefrontal cortices correlated to fear-induced anxiety by approaches of behavior task, neural tracing, molecular biology and electrophysiology in vivo. This psychological stress causes observational mice fears specific to resident mouse and anxiety. This social phobia is associated with the interconnections newly emerged among visual, auditory and medial prefrontal cortices as well as among intramodal neurons. These cortical neurons receive the new synapse innervations from their interconnected neurons alongside the innate synapse innervations, and become to encode the stress signals including battle image and battle sound. The KiF1a knockdown in the medial prefrontal cortex precludes the formations of neuronal infrastructures and social phobia. KiF1a-mediated intracellular transportation in the medial prefrontal cortex is essential for the recruitment of associative memory neurons that encode fear scenes and anxiety. Highlight Psychological stress induces fears and interconnections among sensory and prefrontal cortices. Associative memory neurons in these cortices are recruited to encode fear scenes and anxiety. KiF1a-mediated transportation essential for these cellular infrastructures relevant to learned fear. Competing Interest Statement The authors have declared no competing interest. Footnotes In this revised version, we further polished the manuscript to improve clarity and readability. We revised the title, abstract, and Introduction to better present the main ideas and logic of the study. In addition, we added new panels (H and I) to Figure 1 to explain the relationship between fear memory and anxiety under psychological stress conditions. Abbreviations - AMN - associative memory neurons - mPFC - medial prefrontal cortex - VC - visual cortex - AC - auditory cortex - BS - battle sound - BI - battle image - Ob - observer - Con - control - KiF1a - kinesin family member-1a - RIP - resident/intruder paradigm - SIT - social interaction test - EPM - elevated-plus maze - LGB - lateral geniculate body - MGB - medial geniculate body - AP - anteroposterior - D-AP5 - D-(-)-2-Amino-5-Phosphonopentanoic Acid - CNQX - 6-Cyano-7-Nitroquinoxaline-2,3-Dione.