Pattern decorrelation in the mouse medial prefrontal cortex enables social preference and requires MeCP2.

Sociability is crucial for survival, whereas social avoidance is a feature of disorders such as Rett syndrome, which is caused by loss-of-function mutations in MECP2. To understand how a preference for social interactions is encoded, we used in vivo calcium imaging to compare medial prefrontal cortex (mPFC) activity in female wild-type and Mecp2-heterozygous mice during three-chamber tests. We found that mPFC pyramidal neurons in Mecp2-deficient mice are hypo-responsive to both social and nonsocial stimuli. Hypothesizing that this limited dynamic range restricts the circuit's ability to disambiguate coactivity patterns for different stimuli, we suppressed the mPFC in wild-type mice and found that this eliminated both pattern decorrelation and social preference. Conversely, stimulating the mPFC in MeCP2-deficient mice restored social preference, but only if it was sufficient to restore pattern decorrelation. A loss of social preference could thus indicate impaired pattern decorrelation rather than true social avoidance.

Motor training improves coordination and anxiety in symptomatic Mecp2-null mice despite impaired functional connectivity within the motor circuit.

Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by loss of function of the X-linked methyl-CpG­binding protein 2 (MECP2). Several case studies report that gross motor function can be improved in children with RTT through treadmill walking, but whether the MeCP2-deficient motor circuit can support actual motor learning remains unclear. We used two-photon calcium imaging to simultaneously observe layer (L) 2/3 and L5a excitatory neuronal activity in the motor cortex (M1) while mice adapted to changing speeds on a computerized running wheel. Despite circuit hypoactivity and weakened functional connectivity across L2/3 and L5a, the Mecp2-null circuit's firing pattern evolved with improved performance over 2 weeks. Moreover, trained mice became less anxious and lived 20% longer than untrained mice. Because motor deficits and anxiety are core symptoms of RTT, which is not diagnosed until well after symptom onset, these results underscore the benefit of motor learning.

Prognostic Values of Three Equations in Estimating Glomerular Filtration Rates of Patients Undergoing Off-Pump Coronary Artery Bypass Grafting.

BACKGROUND: Renal dysfunction is independently associated with both short-term and long-term mortality after coronary artery bypass grafting (CABG). The estimated glomerular filtration rate (eGFR) is a convenient and effective indicator of renal function. However, the ability of eGFR calculated by various equations to predict the outcomes of patients undergoing off-pump CABG (OPCABG) is still unclear. This study was aimed to compare the predictive ability of in-hospital and long-term mortality in three equations of estimating renal functions after OPCABG. METHODS: Totally, 1362 patients undergoing OPCABG were retrospectively reviewed. Preoperative and postoperative serum creatinine (Scr) levels were detected. The renal function was evaluated by the Cockcroft-Gault (CG) equation, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, and the full-age spectrum (FAS) equation. The endpoints were in-hospital and long-term all-cause mortality rates. Receiver operating characteristic curves, net reclassification index, decision curve analysis (DCA), multivariable logistic model, and Cox regression model were used for comparisons. RESULTS: The CG equation had the significantly highest discriminatory power to predict in-hospital mortality (area under the curve=0.815). Valuable clinical net benefits of the CG equation were greater than the other two equations regardless of before or after operation by DCA. Multivariable logistic and Cox regression analysis illustrated that the eGFR calculated by the CG equation was a significant independent risk factor of both in-hospital mortality (odds ratio=3.390) and long-term mortality (hazard ratio=1.553). CONCLUSION: The CG equation outperformed the FAS and CKD-EPI equations in predicting the mortality of patients after OPCABG. Postoperative renal function was more efficiently predicted compared with the preoperative one.