Mutant mouse models implicate a role for mGluR1/5, prolyl isomerase (Pin1) and Homer1a interactions in wakefulness.

Introduction: Healthy sleep and wake are integral to good health and occur when an organism is able to maintain long bouts of both sleep and wakefulness. Homer proteins have been shown to be important for sleep in both Methods: EEG recordings were used to determine and compare sleep and wake in three different mouse models and their littermate control mice. Mouse models included: mGluR(TS-AA) knock-in mice in which Pin1 binding is prevented and activity-dependent prolyl isomerization of mGluR is inhibited; mGluR(F-R) knock-in mice in which Homer binding is eliminated but Pin1 binding is allowed; and a Homer1a null, mGluR(F-R) double mutant mouse to evaluate whether Pin1 binding can rescue the Homer1a knock-out phenotype. Sleep-wake behavior was analyzed using traditional summary measures and a spike-and-slab mixture distribution to better characterize microarchitecture. Results: Knock-in mGluR(TS-AA) mice display a reduced ability to sustain long bouts of wakefulness during the active lights off period, recapitulating part of the previously observed wake phenotype of the Conclusion: These studies highlight the role of Pin1 binding to mGluR as a potential mechanism in the control of sleep/wake behavior. Future studies should explore whether other binding partners of Homer and mGluR also affect sleep and wake.