Primary cilia are required for the persistence of memory and stabilization of perineuronal nets
Vladimir Jovasevic,
Hui Zhang,
Farahnaz Sananbenesi,
Anita L. Guedea,
Kizhake V. Soman,
John E. Wiktorowicz,
Andre Fischer,
Jelena Radulovic
Affiliations
Vladimir Jovasevic
Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Room 13-100, Montgomery Ward Memorial Building, Chicago, IL 60611, USA; Corresponding author
Hui Zhang
Department of Neuroscience and Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Rose F. Kennedy Center, 1410 Pelham Parkway South, Room 115, Bronx, NY 10461, USA
Farahnaz Sananbenesi
German Center for Neurodegenerative Diseases, Göttingen 37075, Germany
Anita L. Guedea
Department of Psychiatry and Behavioral Sciences, Northwestern University, Chicago, IL 60611, USA
Kizhake V. Soman
Division of Infectious Disease, Department of Internal Medicine, UTMB – Galveston, Galveston, TX 77555, USA
John E. Wiktorowicz
InnovaRegi, LLC, San Jose, CA 95138, USA
Andre Fischer
German Center for Neurodegenerative Diseases, Göttingen 37075, Germany
Jelena Radulovic
Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Room 13-100, Montgomery Ward Memorial Building, Chicago, IL 60611, USA; Department of Neuroscience and Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Rose F. Kennedy Center, 1410 Pelham Parkway South, Room 115, Bronx, NY 10461, USA; Corresponding author
Summary: It is well established that the formation of episodic memories requires multiple hippocampal mechanisms operating on different time scales. Early mechanisms of memory formation (synaptic consolidation) have been extensively characterized. However, delayed mechanisms, which maintain hippocampal activity as memories stabilize in cortical circuits, are not well understood. Here we demonstrate that contrary to the transient expression of early- and delayed-response genes, the expression of cytoskeleton- and extracellular matrix-associated genes remains dynamic even at remote time points. The most profound expression changes clustered around primary cilium-associated and collagen genes. These genes most likely contribute to memory by stabilizing perineuronal nets in the dorsohippocampal CA1 subfield, as revealed by targeted disruptions of the primary cilium or perineuronal nets. The findings show that nonsynaptic, primary cilium-mediated mechanisms are required for the persistence of context memory.
