Impaired persistence of cortical sensory adaptation following repetitive tactile stimulation in the hindlimb somatosensory cortex of Rett syndrome mice.

Reduced response to repeated stimulation (RS) is a signature feature of sensory systems. In this study we examined cortical sensory responses to brief tactile stimulation of the foot/ankle before, during and after periods of RS in young male, young and old female mice. We compared cortical activity in wild-type (WT) mice to mice with mutation in Mecp2 that causes the neurodevelopmental disorder Rett syndrome (RTT). Intrinsic optical signal imaging (IOS) and intracortical local field potential (LFP) measurements revealed reduced cortical responses to test stimuli on the order of 40-50% after 15-min periods of RS. The time-course and magnitude of reduced IOS and LFP to tactile test-stimuli were similar in WT and RTT mice before and during application of RS. However, after cessation of RS, cortical responses remained persistently below pre-stimulation in WT while RTT mice had significantly more rapid and in some cases complete recovery with an hour of rest. LFP responses to each stimulus in a 7-stimulus test-train characteristically decline. Examining the buildup of this adaptation during test-trains revealed that while the response to the first stimulus in the test-train was generally consistent, responses to successive stimuli in the test-train declined more rapidly after application of RS. This increased adaptation during test-trains persisted in WT mice and reversed more rapidly in RTT mice suggesting that persistent cortical sensory adaptation results from enhancement of processes responsible for short-term adaptation. The lack of persistent cortical sensory adaptation in RTT mice may reflect reduced long-term plasticity within central somatosensory processing circuits.