Impaired thalamic burst firing in fragile X syndrome

The thalamus performs a critical role in sensory processing by gating the flow of sensory information to the neocortex and directing sensory-guided behaviors, functions that are disrupted in people with autism spectrum disorder (ASD). We have identified cellular changes in thalamic neurons in a mouse model of fragile X syndrome (FX) that alter how the thalamus transmits sensory information to neocortical circuits. In awake wild-type (WT) mice, thalamic neurons shift between two firing modes, burst and tonic, which may gate input to the neocortex. Thalamic neurons in FX mice, however, do not shift between these modes and instead fire primarily in the tonic mode. Voltage-clamp recordings reveal that macroscopic Ca²⁺ currents are significantly smaller at hyperpolarized membrane potentials in FX LGN neurons compared to those of the WT. In agreement with the voltage-clamp results, we demonstrate that the Ca²⁺-dependent low-threshold spike, which underlies normal bursting, is reduced or absent at membrane potentials at or around the resting membrane potential.