Hippocampal Place Cell Sequences Are Impaired in a Rat Model of Fragile X Syndrome

Abstract

Fragile X syndrome (FXS) is a neurodevelopmental disorder that can cause impairments in spatial cognition and memory. The hippocampus is thought to support spatial cognition through the activity of place cells, neurons with spatial receptive fields. Coordinated firing of place cell populations is organized by different oscillatory patterns in the hippocampus during specific behavioral states. Theta rhythms organize place cell populations during awake exploration. Sharp wave-ripples organize place cell population reactivation during waking rest. Here, we examined the coordination of CA1 place cell populations during active behavior and subsequent rest in a rat model of FXS ( Fmr1 knock-out rats). While the organization of individual place cells by the theta rhythm was normal, the coordinated activation of sequences of place cells during individual theta cycles was impaired in Fmr1 knock-out rats. Furthermore, the subsequent replay of place cell sequences was impaired during waking rest following active exploration. Together, these results expand our understanding of how genetic modifications that model those observed in FXS affect hippocampal physiology and suggest a potential mechanism underlying impaired spatial cognition in FXS.