Impaired thalamic burst firing in Fragile X syndrome

Abstract

The thalamus performs a critical role in sensory processing by gating the flow of sensory information to the neocortex and directing sensory-driven behaviors; functions which are disrupted in people with autism spectrum disorders (ASD). We have identified cellular changes in thalamic neurons in a mouse model of Fragile X syndrome (FX), the leading monogenic cause of ASD, that alter how the thalamus transmits sensory information to neocortical circuits. In awake animals, thalamic relay cells gate input by shifting between two firing modes: burst and tonic. Relay cells in FX mice, however, do not shift between these modes and instead operate primarily in the tonic mode. We demonstrate that the lack of burst mode firing is caused by a shift in the voltage sensitivity for the Ca2+-dependent low threshold spike, which underlies normal burst firing.