Visual Experience-Dependent Oscillations and Underlying Circuit Connectivity Changes Are Impaired in Fmr1 KO Mice

Fragile X syndrome (FX), the most common inherited form of autism and intellectual disability, is a condition associated with visual perceptual learning deficits. We recently discovered that perceptual experience can encode visual familiarity via persistent low-frequency oscillations in the mouse primary visual cortex (V1). Here, we combine this paradigm with a multifaceted experimental approach to identify neurophysiological impairments of these oscillations in FX mice. Extracellular recordings reveal shorter durations, lower power, and lower frequencies of peak oscillatory activity in FX mice. Directed information analysis of extracellularly recorded spikes reveals differences in functional connectivity from multiple layers in FX mice after the perceptual experience. Channelrhodopsin-2 assisted circuit mapping (CRACM) reveals increased synaptic strength from L5 pyramidal onto L4 fast-spiking cells after experience in wild-type (WT), but not FX, mice. These results suggest differential encoding of visual stimulus familiarity in FX via persistent oscillations and identify circuit connections that may underlie these changes. [Display omitted] •Experience-dependent oscillations are reduced in magnitude and duration in FX mice•A frequency shift is found in oscillations from FX mice•Functional connections onto L4 FS cells are weaker in FX mice following experience•L5 Pyr to L4 FS synapse is strengthened after experience in WT, but not in FX, mice Kissinger et al. study perceptual experience-dependent visual cortical oscillations in Fragile X mice using extracellular electrophysiology, revealing decreased oscillatory magnitudes and altered temporal profiles in Fragile X mice. Additionally, they perform a cross-layer functional connectivity analysis of these data and channelrhodopsin-2 assisted circuit mapping to identify underlying circuit differences.