Altered vagus nerve stimulation evoked locus coeruleus activity in a rodent model of Rett syndrome

Rett syndrome is a neurodevelopmental disorder characterized by seemingly typical development followed by a profound regression, including the loss of language and motor skills and the onset of seizures. Following this regression, intensive intervention is typically ineffective, resulting in the need for novel therapeutics. One potential intervention combines vagus nerve stimulation (VNS) with rehabilitative training, evoking synaptic plasticity and cortical reorganization in an animal model of Rett syndrome. VNS functions by inducing rapid, phasic activation of the locus coeruleus (LC) to facilitate plasticity in circuits engaged by the concurrent rehabilitative training. However, because baseline LC activity is altered in Rett syndrome, it would be valuable to characterize VNS-driven LC activity in Rett models.

Here we describe VNS-evoked neural activity in the LC of a rodent model of Rett syndrome (Mecp2^+/- rats) and age-matched wild-type (WT) littermate controls across a range of VNS parameters.

Mecp2^+/- rats demonstrate significant deficits in VNS-evoked LC responses, including an increased activation threshold. LC evoked responses can be increased by changing the parameters of VNS delivery.

These data improve the understanding of LC function in the Mecp2^+/- rat and provide a baseline to begin optimizing neuromodulator-based therapies for individuals with neurodevelopmental disorders.